Review Article

Drug Therapy

Neuraminidase Inhibitors for Influenza

Anne Moscona, M.D.

N Engl J Med 2005; 353:1363-1373September 29, 2005

Article

The impact of influenza infection is felt globally each year when the disease develops in approximately 20 percent of the world's population. In the United States, influenza infections occur in epidemics each winter, generally between late December and early March. Recent events, including human cases of avian influenza, have heightened awareness of the threat of a pandemic and have spurred efforts to develop plans for its control.

Although vaccination is the primary strategy for the prevention of influenza, there are a number of likely scenarios for which vaccination is inadequate and effective antiviral agents would be of the utmost importance. During any influenza season, antigenic drift in the virus may occur after formulation of the year's vaccine has taken place, rendering the vaccine less protective, and outbreaks can more easily occur among high-risk populations. In the course of a pandemic, vaccine supplies would be inadequate. Vaccine production by current methods cannot be carried out with the speed required to halt the progress of a new strain of influenza virus; therefore, it is likely that vaccine would not be available for the first wave of spread of virus.1 Antiviral agents thus form an important part of a rational approach to epidemic influenza and are critical to planning for a pandemic.

Adamantanes and Neuraminidase Inhibitors

Four drugs are currently available for the treatment or prophylaxis of influenza infections: the adamantanes (amantadine and rimantadine) and the newer class of neuraminidase inhibitors (zanamivir [Relenza] and oseltamivir [Tamiflu]). The adamantanes interfere with viral uncoating inside the cell. They are effective only against influenza A and are associated with several toxic effects and with rapid emergence of drug-resistant variants. Adamantane-resistant isolates of influenza A are genetically stable, can be transmitted to susceptible contacts, are as pathogenic as wild-type virus isolates, and can be shed for prolonged periods in immunocompromised patients taking the drug. This potential for the development of resistance especially limits the use of the adamantanes for the treatment of influenza, although the drugs still have a place in planning for prophylaxis during an epidemic.

The neuraminidase inhibitors zanamivir and oseltamivir interfere with the release of progeny influenza virus from infected host cells, a process that prevents infection of new host cells and thereby halts the spread of infection in the respiratory tract (Figure 1Figure 1Mechanism of Action of Neuraminidase Inhibitors.). Since replication of influenza virus in the respiratory tract reaches its peak between 24 and 72 hours after the onset of the illness, drugs such as the neuraminidase inhibitors that act at the stage of viral replication must be administered as early as possible. In contrast to the adamantanes, the neuraminidase inhibitors are associated with very little toxicity and are far less likely to promote the development of drug-resistant influenza. As a class, the neuraminidase inhibitors are effective against all neuraminidase subtypes and, therefore, against all strains of influenza, a key point in epidemic and pandemic preparedness and an important advantage over the adamantanes, which are effective only against sensitive strains of influenza A. These new drugs, if used properly, have great potential for diminishing the effects of influenza infection.

Development of Neuraminidase Inhibitor Molecules

All influenza viruses bear two surface glycoproteins, a hemagglutinin and a neuraminidase, which are the antigens that define the particular strain of influenza. The variation of these molecules over time permits the virus to evade human immune responses and therefore necessitates the formulation of a new vaccine each year. The hemagglutinin is a sialic acid receptor–binding molecule and mediates entry of the virus into the target cell. The neuraminidase — the target molecule of the neuraminidase inhibitor compounds — cleaves the cellular-receptor sialic acid residues to which the newly formed particles are attached (Figure 1). This cleavage releases the viruses, which can now invade new cells. Without neuraminidase, infection would be limited to one round of replication, rarely enough to cause disease. Neuraminidase may also facilitate viral invasion of the upper airways, possibly by cleaving the sialic acid moieties on the mucin that bathes the airway epithelial cells.2

The ability of transition-state analogues of sialic acid to inhibit the influenza neuraminidase was first recognized in the 1970s,3-5 but the design of highly effective inhibitors became feasible when analysis of the three-dimensional structure of influenza neuraminidase6 disclosed the location and structure of the catalytic site. Potent inhibitors such as zanamivir closely mimic the natural substrate, fitting into the active site pocket and engaging the protein in the most energetically favorable interaction.7-9 Zanamivir is administered by oral inhalation, which delivers the drug directly to the respiratory tract. Oseltamivir was developed through modifications to the sialic acid analogue framework (including the addition of a lipophilic side chain) that allow the drug to be used orally.10

Pharmacokinetics

Zanamivir is not bioavailable orally and is marketed as a dry powder for inhalation. It is delivered directly to the respiratory tract through an inhaler (Diskhaler, Glaxo Wellcome) that holds small pouches of the drug. Zanamivir is highly concentrated in the respiratory tract; 10 to 20 percent of the active compound reaches the lungs, and the rest is deposited in the oropharynx. Five to 15 percent of the total dose is absorbed and excreted in the urine,11 resulting in a bioavailability of 2 percent, a feature that is potentially advantageous in situations in which a systemic drug is undesirable. The concentration of the drug in the respiratory tract has been estimated to be more than 1000 times as high as the 50 percent inhibitory concentration (IC₅₀) for neuraminidase; in addition, the inhibitory effect starts within 10 seconds — two favorable features in terms of reducing the likelihood of emergence of drug-resistant variant viruses.

Oseltamivir is available as a capsule or powder for liquid suspension with good oral bioavailability. It is readily absorbed from the gastrointestinal tract, is converted by hepatic esterases to the active form of the compound (oseltamivir carboxylate), and is widely distributed in the body. The half-life is 6 to 10 hours. The drug is excreted primarily through the kidneys; thus, dosing must be modified in patients with renal insufficiency (Table 1Table 1Dosing Schedule of Neuraminidase Inhibitors for the Treatment and Prevention of Influenza, According to Patient's Age and Coexisting Illnesses.). Oseltamivir achieves high plasma levels and thus can act outside the respiratory tract.

Clinical Trials of Zanamivir and Oseltamivir

Treatment of Healthy Adults

An initial 1997 study12 indicated that confirmed cases of influenza could be treated with zanamivir, demonstrating an approximately one-day reduction in the time to alleviation of symptoms. Subsequent studies12-23 in widely diverse geographic locations showed that when otherwise healthy adults with influenza received zanamivir or oseltamivir within 36 to 48 hours after the onset of illness, a decrease in symptomatic illness of one to two days occurred (Table 2Table 2Selected Treatment Trials of Neuraminidase Inhibitors.). One large study in the United States evaluated the efficacy of oseltamivir treatment18 in 629 healthy, nonimmunized adults 18 to 65 years of age who presented with a febrile respiratory illness of no more than 36 hours' duration, along with one respiratory and one constitutional symptom. Influenza was confirmed in 374 of the subjects, and oseltamivir treatment reduced the median duration of illness by more than 30 percent (from 4.3 days to 3 days) and the severity of illness by about 40 percent. There was a reduction in fever and a resolution of symptoms as soon as 24 hours after the initiation of treatment. Furthermore, treated patients had a lower frequency of secondary complications than did untreated patients.

Early initiation of treatment appears to be the most important determinant of treatment efficacy, as demonstrated in the 2003 Immediate Possibility to Access Treatment (IMPACT) study, which directly investigated the relationship between the time to the initiation of oseltamivir therapy and the duration of illness and other efficacy measures in 1426 patients ranging in age from 12 to 70 years.23 Treatment that started within the first 12 hours after the onset of fever shortened the illness by more than three days, as compared with treatment that was started at 48 hours. The initiation of treatment at intermediate times shortened the illness proportionately. The duration of fever, severity of symptoms, and time to return to normal activity also correlated with the time of antiviral intervention, leading to the clear conclusion that treatment initiated at 36 to 48 hours after the onset of symptoms does not fairly reflect the excellent outcomes obtainable with earlier treatment. A large multicenter trial in Japan extended the IMPACT results to treatment of influenza B.25 Early administration of the drug (within 12 hours after the onset of symptoms) appreciably increased the effectiveness of oseltamivir therapy for both influenza A and B, suggesting that prompt identification of illness and initiation of treatment as early as possible should be the goal for the proper use of neuraminidase inhibitors.

Therapy in the Elderly

Do neuraminidase inhibitors reduce morbidity or mortality in the groups considered to be at high risk, including the elderly? A meta-analysis of trials that were conducted before 200213 involving influenza-positive high-risk patients older than 65 years of age or with chronic medical conditions reported that zanamivir reduced the time to the alleviation of symptoms by 2.0 days and that oseltamivir did so by about 0.5 day. A study in Canadian long-term care facilities26 demonstrated that elderly residents — even those who had been immunized against influenza — who were given oseltamivir within 48 hours after the onset of symptoms were considerably less likely to be prescribed antibiotics, to be hospitalized, or to die.

Experiments in animals suggest that the influenza neuraminidase plays a role in the synergism between influenza virus infection and Streptococcus pneumoniae, thus providing a mechanism whereby neuraminidase inhibitors might reduce the incidence of secondary bacterial pneumonia.27 A recent analysis of 10 trials of treatment with oseltamivir (Table 2) revealed that treatment of documented influenza lowered the incidence of related complications involving the lower respiratory tract that required antibiotic therapy and lowered the hospitalization rate from influenza.24

Therapy in Children

In the first trial of neuraminidase inhibitors in children, zanamivir appeared to be effective in shortening the duration and severity of clinically diagnosed influenza symptoms in children between the ages of 5 and 12 years (Table 2).21 A large trial of oseltamivir treatment in children from 1 to 12 years of age with clinically diagnosed influenza of a duration of no more than 48 hours (65 percent with proven influenza22) indicated that treatment reduced the length of illness by 36 hours. The incidence of otitis media, a frequent complication, was reduced by 44 percent. Oseltamivir is currently approved for therapy in children as young as one year of age (Table 1).

Prophylactic Efficacy of Zanamivir and Oseltamivir

Prophylaxis in Healthy Adults

Several large, controlled studies of prophylaxis28-33 have demonstrated that zanamivir and oseltamivir are effective in preventing clinical influenza in healthy adults when the drugs are used either as prophylaxis after exposure for close contacts, such as household members,28-30,33 or as seasonal prophylaxis in the community.31,32 Overall, both oseltamivir and zanamivir were 70 to 90 percent effective in preventing disease when used for prophylaxis either before or after exposure for both influenza A and influenza B13,28-32,34,35 (Table 3Table 3Selected Trials of Prophylaxis with the Use of Neuraminidase Inhibitors.). However, only oseltamivir is currently approved for use as prophylaxis in the United States.

Prophylaxis in High-Risk Elderly or Chronically Ill Populations

There are fewer data on the use of these drugs to prevent disease in the most vulnerable patients, including the elderly.36,37 One important double-blind, placebo-controlled, randomized study36 demonstrated that the use of oseltamivir for seasonal prophylaxis in residential homes for elderly persons led to a 92 percent reduction in the incidence of laboratory-confirmed influenza, even though the great majority of the elderly residents had received the appropriate vaccine for the season. Thus, antiviral prophylaxis provided important additional protection to that conferred by vaccination.36 Efforts to improve early recognition of influenza symptoms in the elderly and rapid response by staff members will enhance the effectiveness of oseltamivir prophylaxis for control of outbreaks in institutions.26,37

Prophylaxis in Children after Exposure

Although currently approved only for prophylaxis in children over the age of 13 years, oseltamivir appears to be very effective for postexposure prophylaxis in children as young as 1 year of age. In a prospective, randomized study that assessed the efficacy of postexposure prophylaxis together with treatment of index cases with oseltamivir29 (Table 3), most illness in contacts began very early (1 to 2 days) after index cases became ill. If patients with known influenza or positive viral cultures at baseline were excluded, the protective efficacy was 80 percent for children one year old or older when compared with treating only index cases. These data highlight the importance of recognizing an exposure before viral replication has begun.

Safety and Dosage of Neuraminidase Inhibitors

In general, zanamivir is well tolerated; studies to date suggest that adverse effects, primarily minor transient upper respiratory and gastrointestinal symptoms, develop in equal numbers of patients in drug and placebo groups (Table 4Table 4Percentage of Patients with Serious or Minor Adverse Effects Associated with the Administration of Neuraminidase Inhibitors.). However, post-licensure reports indicated that zanamivir may cause cough, bronchospasm, and a reversible decrease in pulmonary function in some patients.42 On the other hand, a well-controlled trial demonstrated that the recommended dosages of zanamivir did not adversely affect pulmonary function in patients with respiratory disorders.20 If patients with pulmonary dysfunction do receive zanamivir, it is recommended that they have a fast-acting bronchodilator available and discontinue zanamivir if respiratory difficulty develops. Oseltamivir has few adverse effects when administered for either treatment or prophylaxis.29 The most frequent side effects are transient nausea, vomiting, and abdominal pain, which occur in approximately 5 to 10 percent of patients. Most adverse events occur only once, close to the initiation of therapy, and resolve spontaneously within one to two days.19 The consumption of food does not interfere with the absorption of oseltamivir and may reduce nausea and vomiting. The safety profile among elderly persons is similar to that in persons younger than 65. Dosage recommendations for both medications are presented in Table 1. Although zanamivir currently is available only on a limited basis, future public health planning may change the availability of the drug.

Resistance to the Neuraminidase Inhibitors

A key advantage of the neuraminidase inhibitors, and a major difference from the adamantanes, is that development of resistance is very rare. The global neuraminidase inhibitor susceptibility network (NISN), which coordinates the analysis of clinical isolates collected through the World Health Organization's surveillance network,43 found no influenza isolates with spontaneous resistance to neuraminidase inhibitors.44 Until recently, there was little emergence of resistance during treatment and no resistant viruses isolated from immunocompetent persons who received zanamivir. For oseltamivir, the published frequency of viruses that were isolated after treatment and were resistant to the drug is somewhat higher. About 0.4 percent of treated adults harbored viruses with resistant neuraminidases.

However, more resistant isolates emerged during treatment of children. One study identified resistant isolates in 4 percent of treated children,22 and in a recent study of children treated with oseltamivir in Japan, 9 of 50 treated children harbored viruses with mutations in the neuraminidase gene that encoded drug-resistant neuraminidase proteins.45 If this frequent emergence of resistant mutants is found to be a general occurrence in children, it is a serious concern, especially since children are an important source of the spread of influenza in the community.46 The most clinically relevant question is whether the oseltamivir-resistant viruses are transmissible and pathogenic. To date, no documented transmission of an oseltamivir-resistant virus has occurred between people. Generally, neuraminidase mutations lead to a functionally defective enzyme, which reduces the fitness of the virus and causes decreased pathogenicity, at least in animal models.46,47 However, in the ferret model, resistant variants with the same mutation that is found in some children grew well in both the index ferret and in contact animals and were readily transmitted,47 raising concern that some oseltamivir-resistant mutant viruses might be transmissible during an epidemic.

Strategies for Treatment

Either zanamivir or oseltamivir may be used for treatment of infection with influenza A or influenza B. Current policy issues will inform recommendations for the future use of neuraminidase inhibitors (and the availability of zanamivir, currently in short supply). When surveillance data indicate the presence of an epidemic in the community, either rapid laboratory confirmation of influenza infection or the typical constellation of influenza symptoms can signal the need for the initiation of treatment in adults; of clinical symptoms, the combination of fever and cough had the highest predictive value.48 Rapid diagnostic tests, only recently readily available for use in physicians' offices, use antigen, enzyme, or nucleic acid detection methods.49 Some assays detect only influenza A, whereas others detect both influenza A and influenza B. Results are often available in less than an hour, though the sensitivities vary considerably depending on the specific test.50 Improved diagnostic tests are needed, particularly for elderly people with atypical presentations who may shed little virus in their secretions. Meanwhile, the results from rapid assays should be interpreted in light of the sensitivity of the particular test along with influenza surveillance data from the community.

The neuraminidase inhibitors should be used only when symptoms have occurred within the previous 48 hours and, as discussed above, should ideally be initiated within 12 hours after the start of illness. An exception may be made for critically ill, hospitalized patients with influenza, in whom therapy can be considered even when more time has elapsed, though no controlled data are available to support this practice. Treatment that is based on clinical grounds alone, even in the absence of diagnostic tests, is particularly valuable for high-risk patients. Limiting the use of antiviral treatment to severely ill patients is illogical, since at the earliest stages, when therapy should be started, it cannot be predicted whether influenza in a patient will progress to severe illness. In the case of children, fever, cough, and other respiratory symptoms have little predictive value, since the important pediatric respiratory viral pathogens can cocirculate with influenza; thus, the focus needs to be on rapid access to laboratory diagnosis and initiation of therapy.

Strategies for Prophylaxis

Vaccination remains the primary strategy for the prevention of influenza, and the broadened recommendations should lead to protection of a larger portion of the population. However, although the neuraminidase inhibitors clearly cannot substitute for vaccination, they can be valuable adjuncts. Currently, only oseltamivir is approved for use as prophylaxis in the United States. During community epidemics, household postexposure prophylaxis with oseltamivir is suggested for unvaccinated persons, starting as early as possible but no more than two days after exposure. Wider prophylaxis in the community for up to six weeks during an epidemic (seasonal prophylaxis) is a consideration if the epidemic strain is different from that of the vaccine that was administered. The adamantanes may also be considered for this purpose if the circulating strain is influenza A. Nursing homes and other institutions should initiate institution-wide prophylaxis as soon as possible after influenza is found in the community and should provide prophylaxis to vaccinated as well as unvaccinated residents.26,36,37 Obviously, the feasibility of most of the suggestions made here will depend on the availability of stockpiles of the neuraminidase inhibitors and on future public health decisions.

Exposure to influenza or illness in an infant younger than one year of age presents a quandary. The safety of oseltamivir in infants has not been established, and serious concerns have been raised by the observation that juvenile rats accumulate extremely high levels of oseltamivir in the central nervous system.51 The immature blood–brain barrier of the human infant is permeable and might similarly allow access of the drug to the central nervous system in an unpredictable fashion. Thus, infants less than one year of age cannot be offered oseltamivir for either chemoprophylaxis or therapy unless further studies are done in the appropriate age group. Similar concerns about potential toxicity to the fetus or infant arise in the case of pregnant women or breast-feeding mothers who are exposed to influenza, though it should be feasible to target public health efforts toward vaccination of pregnant women in order to avoid this scenario.

Avian Influenza and Pandemic Planning

Pandemics result from the emergence of an influenza strain to which large numbers of the population have not been exposed. A new virus that can be transmitted readily from person to person and that can cause human disease can potentially lead to an influenza pandemic. Highly pathogenic avian influenza A (H5N1) has now fulfilled two of these three criteria. Although a probable transmission of H5N1 avian influenza from an infected child to two close contacts has been reported,52 sustained human-to-human transmission has not been documented. However, the H5N1 viruses that have now become endemic in Asian domestic fowl are being spread by wild birds and appear unlikely to be eradicable.53 H5N1 viruses are expanding their mammalian host range,54 and sporadic human infections with high fatality rates continue to occur in Vietnam, Thailand, and Cambodia.55 These events increase the alarming likelihood that there will be ample opportunity for further adaptation of H5N1 to human hosts.54,56

Antiviral drugs form an important part of a strategy for dealing with an influenza pandemic with a new influenza virus of any origin, including avian influenza. Vaccines that are specific for newly arising strains require several months of preparation, and although the development of a vaccine against H5N1 influenza is under way, none is yet available. In the 1968 and 1977 pandemics, adamantanes were found to have a protective efficacy of around 70 percent, only slightly lower than the efficacy reported during the interpandemic period.57 The protective efficacy of the neuraminidase inhibitors during a pandemic would be expected to be at least as high as that of the adamantanes. The markedly lower rate of emergent resistance and lack of spontaneous resistance to the neuraminidase inhibitors make them the drugs of choice. The 2004 avian H5N1 viruses are resistant to the adamantanes58 but are sensitive to the neuraminidase inhibitors zanamivir and oseltamivir.59,60 Thus, neuraminidase inhibitors are currently the only options for treatment or prophylaxis in humans infected with these strains. Many countries have reportedly stockpiled oseltamivir as part of their pandemic planning. However, there has been a recent report of the isolation of drug-resistant H5N1 virus from a patient treated with oseltamivir in Vietnam.61 This observation suggests that in addition to oseltamivir, zanamivir should be included as part of pandemic preparedness. The neuraminidase inhibitors are also effective against the neuraminidase from the virus that caused the 1918 pandemic62 and the avian viruses that caused outbreaks from 1997 to 1999.63,64

The fact that influenza virus is frequently transmitted from person to person during epidemics before the onset of recognizable symptoms would obviously complicate efforts to control spread during a pandemic.65 However, several strategies are worthy of consideration.54 Although several countries have developed policies that entail treatment of index cases (and possibly prophylaxis of health care workers and other essential workers) as the most efficient use of a limited drug supply, this strategy would not prevent spread. Surveillance might provide advance warning of a new transmissible strain, which could render it feasible to interrupt transmission at the source, delay global spread, and diminish the severity of the initial phase of a pandemic.54,56 Prophylaxis around a localized outbreak to limit the pandemic would require rings of prophylaxis around the contacts of index cases.1,66 Drug stockpiles that can be made rapidly available at the site of an outbreak are essential, and one approach may be to develop an international stockpile managed by the World Health Organization.67 Seasonal prophylaxis and postexposure prophylaxis are other feasible strategies. Targeting high-risk groups may also be considered, although previous pandemic strains have not shown a predilection for the groups most affected during interpandemic periods. Vigilant surveillance, together with clinical and epidemiologic data rapidly applied, as with the recent case of human transmission of avian influenza,52 should guide critical public health decisions.

Current supplies of neuraminidase inhibitors are inadequate for any proposed strategy for pandemic response,1 even for the least satisfactory option of treating only the ill. There is little capacity to increase production in the time of need, and therefore anticipatory stockpiling of drugs and the development of efficient distribution methods in case of need are high priorities. In 2005, we have in hand greatly improved tools for surveillance and diagnosis, as well as highly effective drugs, which is a better state of affairs than that during previous influenza pandemics. Identifying feasible strategies for mass production and distribution of these antiviral agents, combined with research into the incidence and mechanisms of drug resistance, may hold the key to our ability to lessen considerably the impact of the next pandemic.

Source Information

From the Departments of Pediatrics and Microbiology and Immunology, Weill Medical College of Cornell University, New York.

Address reprint requests to Dr. Moscona at the Department of Pediatrics, Box 309, Weill Medical College of Cornell University, 515 E. 71st St., Suite 600D, New York, NY 10021, or at anm2047@med.cornell.edu.

References

References

1. 1

   Hayden FG. Pandemic influenza: is an antiviral response realistic? Pediatr Infect Dis J 2004;23:Suppl:S262-S269
   CrossRef | Medline

2. 2

   Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD. Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. J Virol 2004;78:12665-12667
   CrossRef | Web of Science | Medline

3. 3

   Meindl P, Bodo G, Palese P, Schulman J, Tuppy H. Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Virology 1974;58:457-463
   CrossRef | Web of Science | Medline

4. 4

   Palese P, Compans RW. Inhibition of influenza virus replication in tissue culture by 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid (FANA): mechanism of action. J Gen Virol 1976;33:159-163
   CrossRef | Web of Science | Medline

5. 5

   Palese P, Schulman JL, Bodo G, Meindl P. Inhibition of influenza and parainfluenza virus replication in tissue culture by 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid (FANA). Virology 1974;59:490-498
   CrossRef | Web of Science | Medline

6. 6

   Colman PM, Varghese JN, Laver WG. Structure of the catalytic and antigenic sites in influenza virus neuraminidase. Nature 1983;303:41-44
   CrossRef | Web of Science | Medline

7. 7

   Varghese JN, McKimm-Breschkin JL, Caldwell JB, Kortt AA, Colman PM. The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. Proteins 1992;14:327-332
   CrossRef | Web of Science | Medline

8. 8

   von Itzstein M, Wu W-Y, Kok GB, et al. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 1993;363:418-423
   CrossRef | Web of Science | Medline

9. 9

   Varghese JN, Epa VC, Colman PM. Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase. Protein Sci 1995;4:1081-1087
   CrossRef | Web of Science | Medline

10. 10

    Kim CU, Lew W, Williams MA, et al. Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J Am Chem Soc 1997;119:681-690
    CrossRef | Web of Science | Medline

11. 11

    Cass LM, Brown J, Pickford M, et al. Pharmacoscintigraphic evaluation of lung deposition of inhaled zanamivir in healthy volunteers. Clin Pharmacokinet 1999;36:Suppl 1:21-31
    CrossRef | Web of Science | Medline

12. 12

    Hayden FG, Osterhaus AD, Treanor JJ, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. N Engl J Med 1997;337:874-880
    Full Text | Web of Science | Medline

13. 13

    Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG. Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. BMJ 2003;326:1235-1235
    CrossRef | Web of Science | Medline

14. 14

    Monto AS, Fleming DM, Henry D, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza A and B virus infections. J Infect Dis 1999;180:254-261
    CrossRef | Web of Science | Medline

15. 15

    Makela MJ, Pauksens K, Rostila T, et al. Clinical efficacy and safety of the orally inhaled neuraminidase inhibitor zanamivir in the treatment of influenza: a randomized, double-blind, placebo-controlled European study. J Infect 2000;40:42-48
    CrossRef | Web of Science | Medline

16. 16

    The MIST (Management of Influenza in the Southern Hemisphere Trialist) Study Group. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections. Lancet 1998;352:1877-1881[Erratum, Lancet 1999;353:504, 1104.]
    CrossRef | Web of Science | Medline

17. 17

    Matsumoto K, Ogawa N, Nerome K, et al. Safety and efficacy of the neuraminidase inhibitor zanamivir in treating influenza virus infection in adults: results from Japan. Antivir Ther 1999;4:61-68
    Web of Science | Medline

18. 18

    Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. JAMA 2000;283:1016-1024
    CrossRef | Web of Science | Medline

19. 19

    Nicholson KG, Aoki FY, Osterhaus AD, et al. Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. Lancet 2000;355:1845-1850[Erratum, Lancet 2000;356:1856.]
    CrossRef | Web of Science | Medline

20. 20

    Murphy KR, Eivindson A, Pauksens K, et al. Efficacy and safety of inhaled zanamivir for the treatment of influenza in patients with asthma or chronic obstructive pulmonary disease: a double-blind, randomised, placebo-controlled, multicentre study. Clin Drug Investig 2000;20:337-349
    CrossRef | Web of Science

21. 21

    Hedrick JA, Barzilai A, Behre U, et al. Zanamivir for treatment of symptomatic influenza A and B infection in children five to twelve years of age: a randomized controlled trial. Pediatr Infect Dis J 2000;19:410-417
    CrossRef | Web of Science | Medline

22. 22

    Whitley RJ, Hayden FG, Reisinger KS, et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 2001;20:127-133[Erratum, Pediatr Infect Dis J 2001;20:421.]
    CrossRef | Web of Science | Medline

23. 23

    Aoki FY, Macleod MD, Paggiaro P, et al. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 2003;51:123-129
    CrossRef | Web of Science | Medline

24. 24

    Kaiser L, Wat C, Mills T, Mahoney P, Ward P, Hayden F. Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med 2003;163:1667-1672
    CrossRef | Web of Science | Medline

25. 25

    Kawai N, Ikematsu H, Iwaki N, et al. Factors influencing the effectiveness of oseltamivir and amantadine for the treatment of influenza: a multicenter study from Japan of the 2002-2003 influenza season. Clin Infect Dis 2005;40:1309-1316
    CrossRef | Web of Science | Medline

26. 26

    Bowles SK, Lee W, Simor AE, et al. Use of oseltamivir during influenza outbreaks in Ontario nursing homes, 1999-2000. J Am Geriatr Soc 2002;50:608-616
    CrossRef | Web of Science | Medline

27. 27

    McCullers JA, Bartmess KC. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J Infect Dis 2003;187:1000-1009
    CrossRef | Web of Science | Medline

28. 28

    Hayden FG, Gubareva LV, Monto AS, et al. Inhaled zanamivir for the prevention of influenza in families. N Engl J Med 2000;343:1282-1289
    Full Text | Web of Science | Medline

29. 29

    Hayden FG, Belshe R, Villanueva C, et al. Management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis. J Infect Dis 2004;189:440-449
    CrossRef | Web of Science | Medline

30. 30

    Welliver R, Monto AS, Carewicz O, et al. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. JAMA 2001;285:748-754
    CrossRef | Web of Science | Medline

31. 31

    Monto AS, Robinson DP, Herlocher ML, Hinson JM Jr, Elliott MJ, Crisp A. Zanamivir in the prevention of influenza among healthy adults: a randomized controlled trial. JAMA 1999;282:31-35
    CrossRef | Web of Science | Medline

32. 32

    Hayden FG, Atmar RL, Schilling M, et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med 1999;341:1336-1343
    Full Text | Web of Science | Medline

33. 33

    Monto AS, Pichichero ME, Blanckenberg SJ, et al. Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households. J Infect Dis 2002;186:1582-1588
    CrossRef | Web of Science | Medline

34. 34

    Oxford J, Balasingam S, Lambkin R. A new millennium conundrum: how to use a powerful class of influenza anti-neuraminidase drugs (NAIs) in the community. J Antimicrob Chemother 2004;53:133-136
    CrossRef | Web of Science | Medline

35. 35

    Langley JM, Faughnan ME. Prevention of influenza in the general population. CMAJ 2004;171:1213-1222
    CrossRef | Web of Science | Medline

36. 36

    Peters PH Jr, Gravenstein S, Norwood P, et al. Long-term use of oseltamivir for the prophylaxis of influenza in a vaccinated frail older population. J Am Geriatr Soc 2001;49:1025-1031
    CrossRef | Web of Science | Medline

37. 37

    Monto AS, Rotthoff J, Teich E, et al. Detection and control of influenza outbreaks in well-vaccinated nursing home populations. Clin Infect Dis 2004;39:459-464
    CrossRef | Web of Science | Medline

38. 38

    Harper SA, Fukuda K, Uyeki TM, et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2004;53:1-40
    Medline

39. 39

    Relenza (zanamivir for inhalation). Research Triangle Park, N.C.: Glaxo Wellcome, 2001.
    

40. 40

    Hayden FG, Treanor JJ, Fritz RS, et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA 1999;282:1240-1246
    CrossRef | Web of Science | Medline

41. 41

    Tamiflu (oseltamivir phosphate) capsules. Nutley, N.J.: Roche Laboratories, 2000 (package insert).
    

42. 42

    Freund B, Gravenstein S, Elliott M, Miller I. Zanamivir: a review of clinical safety. Drug Saf 1999;21:267-281
    CrossRef | Web of Science | Medline

43. 43

    Zambon M, Hayden FG. Position statement: global neuraminidase inhibitor susceptibility network. Antiviral Res 2001;49:147-156
    CrossRef | Web of Science | Medline

44. 44

    McKimm-Breschkin J, Trivedi T, Hampson A, et al. Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir. Antimicrob Agents Chemother 2003;47:2264-2272
    CrossRef | Web of Science | Medline

45. 45

    Kiso M, Mitamura K, Sakai-Tagawa Y, et al. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet 2004;364:759-765
    CrossRef | Web of Science | Medline

46. 46

    Moscona A. Oseltamivir-resistant influenza? Lancet 2004;364:733-734
    CrossRef | Web of Science | Medline

47. 47

    Herlocher ML, Truscon R, Elias S, et al. Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J Infect Dis 2004;190:1627-1630
    CrossRef | Web of Science | Medline

48. 48

    Monto AS, Gravenstein S, Elliott M, Colopy M, Schweinle J. Clinical signs and symptoms predicting influenza infection. Arch Intern Med 2000;160:3243-3247
    CrossRef | Web of Science | Medline

49. 49

    Cox NJ, Subbarao K. Influenza. Lancet 1999;354:1277-1282
    CrossRef | Web of Science | Medline

50. 50

    Storch GA. Rapid diagnostic tests for influenza. Curr Opin Pediatr 2003;15:77-84
    CrossRef | Web of Science | Medline

51. 51

    Health Sciences Authority. Product safety alert: new preclinical findings on oseltamivir. March 2004. (Accessed September 2, 2005, at: http://www.hsa.gov.sg/docs/safetyalert_oseltamivir_Mar04.pdf.)
    

52. 52

    Ungchusak K, Auewarakul P, Dowell SF, et al. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med 2005;352:333-340
    Full Text | Web of Science | Medline

53. 53

    Li KS, Guan Y, Wang J, et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 2004;430:209-213
    CrossRef | Web of Science | Medline

54. 54

    Stohr K. Avian influenza and pandemics -- research needs and opportunities. N Engl J Med 2005;352:405-407
    Full Text | Web of Science | Medline

55. 55

    World Health Organization. Cumulative number of confirmed human cases of avian Influenza A/(H5N1) reported to WHO. 2005. (Accessed September 2, 2005, at http://www.who.int/csr/disease/avian_influenza/country/cases_table_2005_08_05/en/index.html.)
    

56. 56

    Monto AS. The threat of an avian influenza pandemic. N Engl J Med 2005;352:323-325[Erratum, N Engl J Med 2005;352:1056.]
    Full Text | Web of Science | Medline

57. 57

    Hayden FG. Perspectives on antiviral use during pandemic influenza. Philos Trans R Soc Lond B Biol Sci 2001;356:1877-1884
    CrossRef | Web of Science | Medline

58. 58

    Centers for Disease Control and Prevention. Update on influenza A(H5N1) and SARS: interim recommendations for enhanced U.S. surveillance, testing, and infection controls. February 3, 2004. (Accessed September 2, 2005, at http://www.cdc.gov/flu/avian/professional/han020302.htm.)
    

59. 59

    Commonwealth Scientific and Industrial Research Organization. CSIRO based drug effective against bird flu. (Accessed September 2, 2005, at http://www.csiro.au/index.asp?type=mediaRelease&id=PrBirdFlu5&stylesheet=mediaRelease.)
    

60. 60

    Trampuz A, Prabhu RM, Smith TF, Baddour LM. Avian influenza: a new pandemic threat? Mayo Clin Proc 2004;79:523-530[Erratum, Mayo Clin Proc 2004;79:833.]
    CrossRef | Web of Science | Medline

61. 61

    World Health Organization. WHO inter-country consultation: influenza A/H5N1 in humans in Asia, Manila May 6th-7th 2005. (Accessed September 2, 2005, at http://www.who.int/csr/disease/avian_influenza/H5N1IntercountryAssessment.pdf.)
    

62. 62

    Tumpey TM, Garcia-Sastre A, Mikulasova A, et al. Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus. Proc Natl Acad Sci U S A 2002;99:13849-13854
    CrossRef | Web of Science | Medline

63. 63

    Leneva IA, Goloubeva O, Fenton RJ, Tisdale M, Webster RG. Efficacy of zanamivir against avian influenza A viruses that possess genes encoding H5N1 internal proteins and are pathogenic in mammals. Antimicrob Agents Chemother 2001;45:1216-1224
    CrossRef | Web of Science | Medline

64. 64

    Leneva IA, Roberts N, Govorkova EA, Goloubeva OG, Webster RG. The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses. Antiviral Res 2000;48:101-115
    CrossRef | Web of Science | Medline

65. 65

    Mills CE, Robins JM, Lipsitch M. Transmissibility of 1918 pandemic influenza. Nature 2004;432:904-906
    CrossRef | Web of Science | Medline

66. 66

    Balicer RD, Huerta M, Grotto I. Tackling the next influenza pandemic. BMJ 2004;328:1391-1392
    CrossRef | Web of Science | Medline

67. 67

    World Health Organization. WHO consultation on priority public health interventions before and during an influenza pandemic. April 2004. (Accessed September 2, 2005 at: http://www.who.int/csr/disease/avian_influenza/consultation/en/.)
    

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   CrossRef

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   CrossRef

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   CrossRef

6. 6

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   CrossRef

7. 7

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   CrossRef

8. 8

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   CrossRef

9. 9

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   CrossRef

10. 10

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    CrossRef

11. 11

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    CrossRef

12. 12

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    CrossRef

13. 13

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    CrossRef

14. 14

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    CrossRef

15. 15

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    CrossRef

16. 16

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    CrossRef

17. 17

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    CrossRef

18. 18

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    CrossRef

19. 19

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    CrossRef

20. 20

    Gerard K.-M. Goh, Bin Xue, A. K. Dunker, Vladimir N. Uversky. 2011. Structural Disorder in Proteins from Influenza Virus. , 169-200.
    CrossRef

21. 21

    2011. Bibliography. , 211-244.
    CrossRef

22. 22

    Amy C. Anderson. (2011) Winning the Arms Race by Improving Drug Discovery against Mutating Targets. ACS Chemical Biology111111091236007
    CrossRef

23. 23

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    CrossRef

24. 24

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    CrossRef

25. 25

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    CrossRef

26. 26

    Nand Kishore Gupta, Priti Tomar, Vikas Sharma, Vinod Kumar Dixit. (2011) Development and characterization of chitosan coated poly-(ɛ-caprolactone) nanoparticulate system for effective immunization against influenza. Vaccine 29:48, 9026-9037
    CrossRef

27. 27

    S. Towers, K. Vogt Geisse, Y. Zheng, Z. Feng. (2011) Antiviral treatment for pandemic influenza: Assessing potential repercussions using a seasonally forced SIR model. Journal of Theoretical Biology 289, 259-268
    CrossRef

28. 28

    James R. Smith, Craig R. Rayner, Barbara Donner, Martina Wollenhaupt, Klaus Klumpp, Regina Dutkowski. (2011) Oseltamivir in seasonal, pandemic, and avian influenza: a comprehensive review of 10-years clinical experience. Advances in Therapy 28:11, 927-959
    CrossRef

29. 29

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    CrossRef

30. 30

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    CrossRef

31. 31

    Shohreh Nafisi, Tahereh Sadigh Vishkaee. (2011) Study on the interaction of tamiflu and oseltamivir carboxylate with human serum albumin. Journal of Photochemistry and Photobiology B: Biology 105:1, 34-39
    CrossRef

32. 32

    Ross Vlahos, John Stambas, Stavros Selemidis. (2011) Suppressing production of reactive oxygen species (ROS) for influenza A virus therapy. Trends in Pharmacological Sciences
    CrossRef

33. 33

    Trang Truc Nguyen, Binh Khanh Mai, Mai Suan Li. (2011) Study of Tamiflu Sensitivity to Variants of A/H5N1 Virus Using Different Force Fields. Journal of Chemical Information and Modeling 51:9, 2266-2276
    CrossRef

34. 34

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    CrossRef

35. 35

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    CrossRef

36. 36

    Kathryn A. Radigan, Richard G. Wunderink. (2011) Epidemic Viral Pneumonia and Other Emerging Pathogens. Clinics in Chest Medicine 32:3, 451-467
    CrossRef

37. 37

    G.G.U. Rohde. (2011) Influenza. Der Internist 52:9, 1047-1052
    CrossRef

38. 38

    Robin Thomson, Mark von Itzstein. 2011. Discovery and Development of Influenza Virus Sialidase Inhibitor Relenza. , 383-400.
    CrossRef

39. 39

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    CrossRef

40. 40

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    CrossRef

41. 41

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    CrossRef

42. 42

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    CrossRef

43. 43

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    CrossRef

44. 44

    Andrés Antón, Tomás Pumarola. (2011) Influenza in immunocompromised patients: considerations for therapy. Future Virology 6:7, 855-868
    CrossRef

45. 45

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    CrossRef

46. 46

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    CrossRef

47. 47

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    CrossRef

48. 48

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    CrossRef

49. 49

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    CrossRef

50. 50

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    CrossRef

51. 51

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    CrossRef

52. 52

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    CrossRef

53. 53

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    CrossRef

54. 54

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    CrossRef

55. 55

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    CrossRef

56. 56

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    CrossRef

57. 57

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    CrossRef

58. 58

    Johannes Kirchmair, Judith M Rollinger, Klaus R Liedl, Nora Seidel, Andi Krumbholz, Michaela Schmidtke. (2011) Novel neuraminidase inhibitors: identification, biological evaluation and investigations of the binding mode. Future Medicinal Chemistry 3:4, 437-450
    CrossRef

59. 59

    Tom Jefferson, Mark A Jones, Peter Doshi, Chris B Del Mar, Carl J Heneghan, Rokuro Hama, Matthew J Thompson, Tom Jefferson. 2011. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children - a review of clinical study reports. .
    CrossRef

60. 60

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    CrossRef

61. 61

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    CrossRef

62. 62

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    CrossRef

63. 63

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    CrossRef

64. 64

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    CrossRef

65. 65

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    CrossRef

66. 66

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    CrossRef

67. 67

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    CrossRef

68. 68

    Steven M. Smith, John G. Gums. (2010) Antivirals for Influenza. Pediatric Drugs 12:5, 285-299
    CrossRef

69. 69

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    CrossRef

70. 70

    Teresa V. Chan. (2010) The Patient with Sore Throat. Medical Clinics of North America 94:5, 923-943
    CrossRef

71. 71

    Anita Müller, Turhan Markussen, Finn Drabløs, Tor Gjøen, Trond Ø. Jørgensen, Stein Tore Solem, Siri Mjaaland. (2010) Structural and functional analysis of the hemagglutinin-esterase of infectious salmon anaemia virus. Virus Research 151:2, 131-141
    CrossRef

72. 72

    Joanne Embree. (2010) Pandemic 2009 (A)H1N1 influenza (swine flu) — the Manitoba experienceThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.. Biochemistry and Cell Biology 88:4, 589-593
    CrossRef

73. 73

    Michael G Ison. (2010) Influenza, including the novel H1N1, in organ transplant patients. Current Opinion in Infectious Diseases 23:4, 365-373
    CrossRef

74. 74

    Fei Tao, Yinan Zhang, Cuiqing Ma, Ping Xu. (2010) Biotechnological production and applications of N-acetyl-d-neuraminic acid: current state and perspectives. Applied Microbiology and Biotechnology 87:4, 1281-1289
    CrossRef

75. 75

    S. P. Kuster, S. Drews, K. Green, J. Blair, I. Davis, J. Downey, R. Fowler, K. Katz, S. Lapinsky, D. McRitchie, J. Pataki, J. Powis, D. Rose, A. Sarabia, C. Simone, A. Simor, T. Stewart, A. McGeer. (2010) Epidemiology of influenza-associated hospitalization in adults, Toronto, 2007/8. European Journal of Clinical Microbiology & Infectious Diseases 29:7, 835-843
    CrossRef

76. 76

    M. E. Falagas, P. K. Koletsi, E. K. Vouloumanou, P. I. Rafailidis, A. M. Kapaskelis, J. Rello. (2010) Effectiveness and safety of neuraminidase inhibitors in reducing influenza complications: a meta-analysis of randomized controlled trials. Journal of Antimicrobial Chemotherapy 65:7, 1330-1346
    CrossRef

77. 77

    J. D. Bloom, L. I. Gong, D. Baltimore. (2010) Permissive Secondary Mutations Enable the Evolution of Influenza Oseltamivir Resistance. Science 328:5983, 1272-1275
    CrossRef

78. 78

    R. B. Moss, R. T. Davey, R. T. Steigbigel, F. Fang. (2010) Targeting pandemic influenza: a primer on influenza antivirals and drug resistance. Journal of Antimicrobial Chemotherapy 65:6, 1086-1093
    CrossRef

79. 79

    Ming Yang, Hong Mei Wu, Ting Li, Bi Rong Dong, Guan J Liu, Hong Mei Wu. 2010. Interventions for preventing influenza: an overview of Cochrane systematic reviews. .
    CrossRef

80. 80

    David M. Guidot. (2010) A Sigh of Relief About Treating Influenza in Individuals With Alcohol-Use Disorders?. Alcoholism: Clinical and Experimental Researchno-no
    CrossRef

81. 81

    R. Dutkowski, J.R. Smith, B.E. Davies. (2010) Safety and pharmacokinetics of oseltamivir at standard and high dosages. International Journal of Antimicrobial Agents 35:5, 461-467
    CrossRef

82. 82

    Vanessa Correia, Helena Rebelo de Andrade, Luís A. Santos, Angie Lackenby, Maria Zambon. (2010) Antiviral drug profile of seasonal influenza viruses circulating in Portugal from 2004/2005 to 2008/2009 winter seasons. Antiviral Research 86:2, 128-136
    CrossRef

83. 83

    Nazanin Zahra Shafiei Jandaghi, Talat Mokhtari Azad, Maryam Naseri, Jila Yavarian, Rakhshandeh Nategh. (2010) Molecular and genetic characteristics of hemagglutinin and neuraminidase in Iranian 2009 pandemic influenza A(H1N1) viruses. Archives of Virology 155:5, 717-721
    CrossRef

84. 84

    Jimei Ma, Yanying Zhao, Simon Ng, Jing Zhang, Jing Zeng, Aung Than, Peng Chen, Xue-Wei Liu. (2010) Sugar-Based Synthesis of Tamiflu and Its Inhibitory Effects on Cell Secretion. Chemistry - A European Journal 16:15, 4533-4540
    CrossRef

85. 85

    B. E. Davies. (2010) Pharmacokinetics of oseltamivir: an oral antiviral for the treatment and prophylaxis of influenza in diverse populations. Journal of Antimicrobial Chemotherapy 65:Supplement 2, ii5-ii10
    CrossRef

86. 86

    Vanitha A Jagannath, G V Asokan, Zbys Fedorowicz, Jai Shanthini Singaram, Tim WR Lee, Vanitha A Jagannath. 2010. Neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. .
    CrossRef

87. 87

    Ryan Kirkby, Carlo Calabrese, Liz Kaltman, Janet Monnier, Paul Herscu. (2010) Methodological Considerations for Future Controlled Influenza Treatment Trials in Complementary and Alternative Medicine. The Journal of Alternative and Complementary Medicine 16:3, 275-283
    CrossRef

88. 88

    Julio García-Suárez, Yolanda Martín, Marta Callejas, Mario Rodriguez-Dominguez, Juan Carlos Galán, Carmen Burgaleta. (2010) Favourable outcome of pneumonia due to novel influenza A/H1N1 2009 virus in a splenectomised adult patient undergoing therapy for non-Hodgkin lymphoma. British Journal of Haematology 148:5, 808-810
    CrossRef

89. 89

    Shaomin Yan, Guang Wu. (2010) Prediction of Mutation Positions in H5N1 Neuraminidases From Influenza A Virus by Means of Neural Network. Annals of Biomedical Engineering 38:3, 984-992
    CrossRef

90. 90

    Lothar Lindemann, Helmut Jacobsen, Diana Schuhbauer, Frederic Knoflach, Silvia Gatti, Joseph G. Wettstein, Hansruedi Loetscher, Tom Chu, Martin Ebeling, James C. Paulson, Eric Prinssen, Manfred Brockhaus. (2010) In vitro pharmacological selectivity profile of oseltamivir prodrug (Tamiflu®) and active metabolite. European Journal of Pharmacology 628:1-3, 6-10
    CrossRef

91. 91

    Thomas R. Cate, Yolanda Rayford, Diane Niño, Patricia Winokur, Rebecca Brady, Robert Belshe, Wilbur Chen, Robert L. Atmar, Robert B. Couch. (2010) A high dosage influenza vaccine induced significantly more neuraminidase antibody than standard vaccine among elderly subjects. Vaccine 28:9, 2076-2079
    CrossRef

92. 92

    M. Kiso, K. Takahashi, Y. Sakai-Tagawa, K. Shinya, S. Sakabe, Q. M. Le, M. Ozawa, Y. Furuta, Y. Kawaoka. (2010) T-705 (favipiravir) activity against lethal H5N1 influenza A viruses. Proceedings of the National Academy of Sciences 107:2, 882-887
    CrossRef

93. 93

    Tatiana Baranovich, Reiko Saito, Yasushi Suzuki, Hassan Zaraket, Clyde Dapat, Isolde Caperig-Dapat, Taeko Oguma, Iman Ibrahim Shabana, Takehiko Saito, Hiroshi Suzuki. (2010) Emergence of H274Y oseltamivir-resistant A(H1N1) influenza viruses in Japan during the 2008–2009 season. Journal of Clinical Virology 47:1, 23-28
    CrossRef

94. 94

    J.-F. RAHIER, Y. YAZDANPANAH, N. VIGET, S. TRAVIS, J.-F. COLOMBEL. (2010) Review article: influenza A (H1N1) virus in patients with inflammatory bowel disease. Alimentary Pharmacology & Therapeutics 31:1, 5-10
    CrossRef

95. 95

    Cindy M. Liu, Elizabeth M. Driebe, James Schupp, Erin Kelley, Jack T. Nguyen, James J. McSharry, Qingmei Weng, David M. Engelthaler, Paul S. Keim. (2010) Rapid quantification of single-nucleotide mutations in mixed influenza A viral populations using allele-specific mixture analysis. Journal of Virological Methods 163:1, 109-115
    CrossRef

96. 96

    Michael G Ison. (2009) Anti-influenza therapy: the emerging challenge of resistance. Therapy 6:6, 883-891
    CrossRef

97. 97

    Vanitha A Jagannath, G V Asokan, Zbys Fedorowicz, Jai Shanthini Singaram, Tim WR Lee, Vanitha A Jagannath. 2009. Neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. .
    CrossRef

98. 98

    Maturos Malaisree, Thanyada Rungrotmongkol, Nadtanet Nunthaboot, Ornjira Aruksakunwong, Pathumwadee Intharathep, Panita Decha, Pornthep Sompornpisut, Supot Hannongbua. (2009) Source of oseltamivir resistance in avian influenza H5N1 virus with the H274Y mutation. Amino Acids 37:4, 725-732
    CrossRef

99. 99

    Charlotte D'Souza, Meena Kanyalkar, Mamata Joshi, Evans Coutinho, Sudha Srivastava. (2009) Search for novel neuraminidase inhibitors: Design, synthesis and interaction of oseltamivir derivatives with model membrane using docking, NMR and DSC methods. Biochimica et Biophysica Acta (BBA) - Biomembranes 1788:9, 1740-1751
    CrossRef

100. 100

     Andreas Handel, Ira M. Longini, Rustom Antia. (2009) Intervention strategies for an influenza pandemic taking into account secondary bacterial infections. Epidemics 1:3, 185-195
     CrossRef

101. 101

     Visvaldas Kairys, Michael K. Gilson, Viney Lather, Celia A. Schiffer, Miguel X. Fernandes. (2009) Toward the Design of Mutation-Resistant Enzyme Inhibitors: Further Evaluation of the Substrate Envelope Hypothesis. Chemical Biology & Drug Design 74:3, 234-245
     CrossRef

102. 102

     Timothy Jancel, Scott R. Penzak. (2009) Antiviral Therapy in Patients With Hematologic Malignancies, Transplantation, and Aplastic Anemia. Seminars in Hematology 46:3, 230-247
     CrossRef

103. 103

     Michel Weïwer, Chi-Chang Chen, Melissa M. Kemp, Robert J. Linhardt. (2009) Synthesis and Biological Evaluation of Non-Hydrolyzable 1,2,3-Triazole-Linked Sialic Acid Derivatives as Neuraminidase Inhibitors. European Journal of Organic Chemistry 2009:16, 2611-2620
     CrossRef

104. 104

     Herman J.M. Cools, Jacobijn Gussekloo, Joyce E.M. Remmerswaal, Ed J. Remarque, Aloys C.M. Kroes. (2009) Benefits of increasing the dose of influenza vaccine in residents of long-term care facilities: A randomized placebo-controlled trial. Journal of Medical Virology 81:5, 908-914
     CrossRef

105. 105

     Katja Bauer, Martina Richter, Peter Wutzler, Michaela Schmidtke. (2009) Different neuraminidase inhibitor susceptibilities of human H1N1, H1N2, and H3N2 influenza A viruses isolated in Germany from 2001 to 2005/2006. Antiviral Research 82:1, 34-41
     CrossRef

106. 106

     Maria Angeles Marcos, Mariano Esperatti, Antoni Torres. (2009) Viral pneumonia. Current Opinion in Infectious Diseases 22:2, 143-147
     CrossRef

107. 107

     Michael Piagnerelli, Karim Zouaoui Boudjeltia, Alessandro Rapotec, Thibault Richard, Dany Brohée, Sajida Babar, Vanessa Bouckaert, Anne-Catherine Simon, Jean-Pierre Toko, Therese Walravens, Jean-Louis Vincent, Michel Vanhaeverbeek. (2009) Neuraminidase alters red blood cells in sepsis. Critical Care Medicine 37:4, 1244-1250
     CrossRef

108. 108

     Andrew W. Hill, Robert P. Guralnick, Meredith J.C. Wilson, Farhat Habib, Daniel Janies. (2009) Evolution of drug resistance in multiple distinct lineages of H5N1 avian influenza. Infection, Genetics and Evolution 9:2, 169-178
     CrossRef

109. 109

     Zhengliang L. Wu, Cheryl Ethen, Gregg E. Hickey, Weiping Jiang. (2009) Active 1918 pandemic flu viral neuraminidase has distinct N-glycan profile and is resistant to trypsin digestion. Biochemical and Biophysical Research Communications 379:3, 749-753
     CrossRef

110. 110

     Karen M. Bromfield, Henrik Gradén, Natalie Ljungdahl, Nina Kann. (2009) Synthetic applications of cationic iron and cobalt carbonyl complexes. Dalton Transactions:26, 5051
     CrossRef

111. 111

     Andreas Handel, Ira M. Longini, Rustom Antia. (2009) Antiviral resistance and the control of pandemic influenza: The roles of stochasticity, evolution and model details. Journal of Theoretical Biology 256:1, 117-125
     CrossRef

112. 112

     Timothy Newhouse, Phil S. Baran, Reinhard W. Hoffmann. (2009) The economies of synthesis. Chemical Society Reviews 38:11, 3010
     CrossRef

113. 113

     Liang-Deng Nie, Xiao-Xin Shi. (2009) A novel asymmetric synthesis of oseltamivir phosphate (Tamiflu) from (−)-shikimic acid. Tetrahedron: Asymmetry 20:1, 124-129
     CrossRef

114. 114

     Mark A. Katz, Mark J. Lamias, David K. Shay, Timothy M. Uyeki. (2009) Use of rapid tests and antiviral medications for influenza among primary care providers in the United States. Influenza and Other Respiratory Viruses 3:1, 29-35
     CrossRef

115. 115

     Mahmoud E. S. Soliman, Giuseppe D. Ruggiero, J. Javier Ruiz Pernía, Ian R. Greig, Ian H. Williams. (2009) Computational mutagenesis reveals the role of active-site tyrosine in stabilising a boat conformation for the substrate: QM/MM molecular dynamics studies of wild-type and mutant xylanases. Organic & Biomolecular Chemistry 7:3, 460
     CrossRef

116. 116

     Angie Lackenby, Catherine I Thompson, Jane Democratis. (2008) The potential impact of neuraminidase inhibitor resistant influenza. Current Opinion in Infectious Diseases 21:6, 626-638
     CrossRef

117. 117

     Young Bae Ryu, Marcus J. Curtis-Long, Jin Hyo Kim, Seong Hun Jeong, Min Suk Yang, Keun Woo Lee, Woo Song Lee, Ki Hun Park. (2008) Pterocarpans and flavanones from Sophora flavescens displaying potent neuraminidase inhibition. Bioorganic & Medicinal Chemistry Letters 18:23, 6046-6049
     CrossRef

118. 118

     Susanne Duwe, Brunhilde Schweiger. (2008) A new and rapid genotypic assay for the detection of neuraminidase inhibitor resistant influenza A viruses of subtype H1N1, H3N2, and H5N1. Journal of Virological Methods 153:2, 134-141
     CrossRef

119. 119

     Michael J. Carr, Naomi Sayre, Margaret Duffy, Jeff Connell, William W. Hall. (2008) Rapid molecular detection of the H275Y oseltamivir resistance gene mutation in circulating influenza A (H1N1) viruses. Journal of Virological Methods 153:2, 257-262
     CrossRef

120. 120

     J. Gabbard, N. Velappan, R. Di Niro, J. Schmidt, C.A. Jones, S.M. Tompkins, A.R.M. Bradbury. (2008) A humanized anti-M2 scFv shows protective in vitro activity against influenza. Protein Engineering Design and Selection 22:3, 189-198
     CrossRef

121. 121

     Mohammad Abrar Alam, Yashwant D. Vankar. (2008) Total synthesis of (+)-lentiginosine from d-glucose. Tetrahedron Letters 49:38, 5534-5536
     CrossRef

122. 122

     Marija L. Mihajlovic, Petar M. Mitrasinovic. (2008) Another look at the molecular mechanism of the resistance of H5N1 influenza A virus neuraminidase (NA) to oseltamivir (OTV). Biophysical Chemistry 136:2-3, 152-158
     CrossRef

123. 123

     Q. Zeng, M. A. Langereis, A. L. W. van Vliet, E. G. Huizinga, R. J. de Groot. (2008) Structure of coronavirus hemagglutinin-esterase offers insight into corona and influenza virus evolution. Proceedings of the National Academy of Sciences 105:26, 9065-9069
     CrossRef

124. 124

     Catherine WM Ong, Paul Ananth Tambyah. (2008) Update on antivirals and vaccines for seasonal and potential pandemic use. Expert Review of Respiratory Medicine 2:3, 391-402
     CrossRef

125. 125

     Andrea Milne. (2008) Summary of ‘Neuraminidase inhibitors for preventing and treating influenza in children’. Evidence-Based Child Health: A Cochrane Review Journal 3:2, 583-584
     CrossRef

126. 126

     NJ Matheson, AR Harnden, R Perera, A Sheikh, M Symmonds-Abrahams. (2008) Cochrane review: Neuraminidase inhibitors for preventing and treating influenza in children. Evidence-Based Child Health: A Cochrane Review Journal 3:2, 540-582
     CrossRef

127. 127

     John Beigel, Mike Bray. (2008) Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Research 78:1, 91-102
     CrossRef

128. 128

     Pieter Leyssen, Erik De Clercq, Johan Neyts. (2008) Molecular strategies to inhibit the replication of RNA viruses. Antiviral Research 78:1, 9-25
     CrossRef

129. 129

     D. Low. (2008) Reducing antibiotic use in influenza: challenges and rewards. Clinical Microbiology and Infection 14:4, 298-306
     CrossRef

130. 130

     Arnold S. Monto, Richard J. Whitley. (2008) Seasonal and Pandemic Influenza: A 2007 Update on Challenges and Solutions. Clinical Infectious Diseases 46:7, 1024-1031
     CrossRef

131. 131

     David A. Wetter, Alison J. Bruce, Kathy L. MacLaughlin, Roy S. Rogers. (2008) Ulcus Vulvae Acutum in a 13-Year-Old Girl After Influenza A Infection. SKINmed 7:2, 95-98
     CrossRef

132. 132

     Jayanta Haldar, Jianzhu Chen, Terrence M. Tumpey, Larisa V. Gubareva, Alexander M. Klibanov. (2008) Hydrophobic polycationic coatings inactivate wild-type and zanamivir- and/or oseltamivir-resistant human and avian influenza viruses. Biotechnology Letters 30:3, 475-479
     CrossRef

133. 133

     Paul A. TAMBYAH. (2008) Update on influenza anti-virals. Respirology 13:s1, S19-S21
     CrossRef

134. 134

     A. Chris Krueger, Yibo Xu, Warren M. Kati, Dale J. Kempf, Clarence J. Maring, Keith F. McDaniel, Akhteruzzaman Molla, Debra Montgomery, William E. Kohlbrenner. (2008) Synthesis of potent pyrrolidine influenza neuraminidase inhibitors. Bioorganic & Medicinal Chemistry Letters 18:5, 1692-1695
     CrossRef

135. 135

     Michael G. Ison, Amita Sharma, Jo-Anne O. Shepard, John C. Wain, Leo C. Ginns. (2008) Outcome of Influenza Infection Managed With Oseltamivir in Lung Transplant Recipients. The Journal of Heart and Lung Transplantation 27:3, 282-288
     CrossRef

136. 136

     Yacine Abed, Benjamin Nehmé, Mariana Baz, Guy Boivin. (2008) Activity of the neuraminidase inhibitor A-315675 against oseltamivir-resistant influenza neuraminidases of N1 and N2 subtypes. Antiviral Research 77:2, 163-166
     CrossRef

137. 137

     Pramod C. Nair, M. Elizabeth Sobhia. (2008) Quantitative structure activity relationship studies on thiourea analogues as influenza virus neuraminidase inhibitors. European Journal of Medicinal Chemistry 43:2, 293-299
     CrossRef

138. 138

     Anne Moscona. (2008) Medical Management of Influenza Infection. Annual Review of Medicine 59:1, 397-413
     CrossRef

139. 139

     S.Y. Oh, B. Cornell, D. Smith, G. Higgins, C.J. Burrell, T.W. Kok. (2008) Rapid detection of influenza A virus in clinical samples using an ion channel switch biosensor. Biosensors and Bioelectronics 23:7, 1161-1165
     CrossRef

140. 140

     Francisco López-Medrano, José María Aguado. (2008) Virus respiratorios: los más frecuentes, los más olvidados. Enfermedades Infecciosas y Microbiología Clínica 26:2, 67-68
     CrossRef

141. 141

     Márcia G Alves Galvão, Marilene Augusta Rocha Crispino Santos, Antonio JL Alves da Cunha, Antonio JL Alves da Cunha. 2008. Amantadine and rimantadine for influenza A in children and the elderly. .
     CrossRef

142. 142

     Kevin C. Worley, Scott W. Roberts, Roger E. Bawdon. (2008) The Metabolism and Transplacental Transfer of Oseltamivir in the Ex Vivo Human Model. Infectious Diseases in Obstetrics & Gynecology 2008, 1-5
     CrossRef

143. 143

     Maki Sato, Reiko Saito, Isamu Sato, Naohito Tanabe, Yugo Shobugawa, Asami Sasaki, Danjuan Li, Yasushi Suzuki, Mizuho Sato, Takatsugu Sakai, Taeko Oguma, Hiroki Tsukada, Fumitake Gejyo, Hiroshi Suzuki. (2008) Effectiveness of Oseltamivir Treatment among Children with Influenza A or B Virus Infections during Four Successive Winters in Niigata City, Japan. The Tohoku Journal of Experimental Medicine 214:2, 113-120
     CrossRef

144. 144

     Petr G. Deryabin, Dmitry K. Lvov, Andrey G. Botikov, Vadim Ivanov, Tatiana Kalinovsky, Matthias Rath, Aleksandra Niedzwiecki. (2008) Effects of a nutrient mixture on infectious properties of the highly pathogenic strain of avian influenza virus A/H5N1. BioFactors 33:2, 85-97
     CrossRef

145. 145

     M.W. Roomi, R.J. Jariwalla, T. Kalinovsky, N. Roomi, A. Niedzwiecki, M. Rath. (2008) Inhibition of cellular invasive parameters in influenza A virus-infected MDCK and vero cells by a nutrient mixture. BioFactors 33:1, 61-75
     CrossRef

146. 146

     Irene M. Lagoja, Erik De Clercq. (2008) Anti-influenza virus agents: Synthesis and mode of action. Medicinal Research Reviews 28:1, 1-38
     CrossRef

147. 147

     Mee Soo Chang, Jun Hee Woo. (2008) Clinical Use of Tamiflu (Oseltamivir). Journal of the Korean Medical Association 51:8, 757
     CrossRef

148. 148

     A. McGeer, K. A. Green, A. Plevneshi, A. Shigayeva, N. Siddiqi, J. Raboud, D. E. Low, . (2007) Antiviral Therapy and Outcomes of Influenza Requiring Hospitalization in Ontario, Canada. Clinical Infectious Diseases 45:12, 1568-1575
     CrossRef

149. 149

     Michael Gardam, Camille Lemieux. (2007) Transmission of influenza A in human beings – Authors' reply. The Lancet Infectious Diseases 7:12, 761-763
     CrossRef

150. 150

     Kozo Yasui, Yoshiro Amano, Isaki Minami, Shinichi Nakamura, Yohei Akazawa, Noriko Uchida. (2007) Recent changes in the trends of seasonal influenza outbreaks in the Nagano Prefectural area of Japan: an oseltamivir effect?. Journal of Infection and Chemotherapy 13:6, 429-431
     CrossRef

151. 151

     Robert C. Moellering, John R. Graybill, John E. McGowan, Lawrence Corey. (2007) Antimicrobial resistance prevention initiative—an update: Proceedings of an expert panel on resistance. American Journal of Infection Control 35:9, S1-S23
     CrossRef

152. 152

     Phillip Andrew Reece. (2007) Neuraminidase inhibitor resistance in influenza viruses. Journal of Medical Virology 79:10, 1577-1586
     CrossRef

153. 153

     James M. McCaw, Jodie McVernon. (2007) Prophylaxis or treatment? Optimal use of an antiviral stockpile during an influenza pandemic. Mathematical Biosciences 209:2, 336-360
     CrossRef

154. 154

     Richard J Whitley. (2007) The role of oseltamivir in the treatment and prevention of influenza in children. Expert Opinion on Drug Metabolism & Toxicology 3:5, 755-767
     CrossRef

155. 155

     Zong-ying Liu, Bo Wang, Li-xun Zhao, Yu-huan Li, Hua-yi Shao, Hong Yi, Xue-fu You, Zhuo-rong Li. (2007) Synthesis and anti-influenza activities of carboxyl alkoxyalkyl esters of 4-guanidino-Neu5Ac2en (zanamivir). Bioorganic & Medicinal Chemistry Letters 17:17, 4851-4854
     CrossRef

156. 156

     Katja Bauer, Christina Schrader, Jochen Suess, Peter Wutzler, Michaela Schmidtke. (2007) Neuraminidase inhibitor susceptibility of porcine H3N2 influenza A viruses isolated in Germany between 1982 and 1999. Antiviral Research 75:3, 219-226
     CrossRef

157. 157

     Jindrich Cinatl, Martin Michaelis, Hans W. Doerr. (2007) The threat of avian influenza a (H5N1): part II: Clues to pathogenicity and pathology. Medical Microbiology and Immunology 196:4, 191-201
     CrossRef

158. 158

     Jindrich Cinatl, Martin Michaelis, Hans W. Doerr. (2007) The threat of avian influenza A (H5N1). Part III: antiviral therapy. Medical Microbiology and Immunology 196:4, 203-212
     CrossRef

159. 159

     Craig LaForce, Choy Y. Man, Frederick W. Henderson, Janet E. McElhaney, Frank C. Hampel, Robert Bettis, Laila Kudule, Julia Harris, Philip Yates, Margaret Tisdale, Alison Webster. (2007) Efficacy and Safety of Inhaled Zanamivir in the Prevention of Influenza in Community-Dwelling, High-Risk Adult and Adolescent Subjects: A 28-day, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Clinical Therapeutics 29:8, 1579-1590
     CrossRef

160. 160

     Cesare Accinelli, Anna Barra Caracciolo, Paola Grenni. (2007) Degradation of the antiviral drug oseltamivir carboxylate in surface water samples. International Journal of Environmental Analytical Chemistry 87:8, 579-587
     CrossRef

161. 161

     Robert C. Moellering, John R. Graybill, John E. McGowan, Lawrence Corey. (2007) Antimicrobial Resistance Prevention Initiative—An Update: Proceedings of an Expert Panel on Resistance. The American Journal of Medicine 120:7, S4-S25
     CrossRef

162. 162

     Paul J. Drinka, Tom Haupt. (2007) Emergence of Rimantadine-Resistant Virus Within 6 Days of Starting Rimantadine Prophylaxis with Oseltamivir Treatment of Symptomatic Cases. Journal of the American Geriatrics Society 55:6, 923-926
     CrossRef

163. 163

     Stephen S Morse. (2007) The US pandemic influenza implementation plan at six months. Nature Medicine 13:6, 681-684
     CrossRef

164. 164

     Tomoshige Kino, George P. Chrousos. (2007) Virus-mediated modulation of the host endocrine signaling systems: clinical implications. Trends in Endocrinology & Metabolism 18:4, 159-166
     CrossRef

165. 165

     R. F. Chemaly, H. A. Torres, E. A. Aguilera, G. Mattiuzzi, M. Cabanillas, H. Kantarjian, V. Gonzalez, A. Safdar, I. I. Raad. (2007) Neuraminidase Inhibitors Improve Outcome of Patients with Leukemia and Influenza: An Observational Study. Clinical Infectious Diseases 44:7, 964-967
     CrossRef

166. 166

     Nathaniel Hupert, Daniel Wattson, Jason Cuomo, Samuel Benson. (2007) Anticipating Demand for Emergency Health Services due to Medication-related Adverse Events after Rapid Mass Prophylaxis Campaigns. Academic Emergency Medicine 14:3, 268-274
     CrossRef

167. 167

     Ajay Bhatia, Richard E. Kast. (2007) How influenza’s neuraminidase promotes virulence and creates localized lung mucosa immunodeficiency. Cellular & Molecular Biology Letters 12:1, 111-119
     CrossRef

168. 168

     Geertjan Wesseling. (2007) Occasional review: Influenza in COPD: pathogenesis, prevention, and treatment. International Journal of COPD 2:1, 5-10
     CrossRef

169. 169

     Guy Vernet. (2007) Use of molecular assays for the diagnosis of influenza. Expert Review of Anti-infective Therapy 5:1, 89-104
     CrossRef

170. 170

     Richard A Martinello. (2007) Preparing for avian influenza. Current Opinion in Pediatrics 19:1, 64-70
     CrossRef

171. 171

     Nicholas J Matheson, Anthony Harnden, Rafael Perera, Aziz Sheikh, Mkael Symmonds-Abrahams, Nicholas J Matheson. 2007. Neuraminidase inhibitors for preventing and treating influenza in children. .
     CrossRef

172. 172

     Jeanine P. Wiener-Kronish. (2007) Infection Control for the Anesthesiologist. ASA Refresher Courses in Anesthesiology 35:1, 219-225
     CrossRef

173. 173

     R. J. Jariwalla, M. W. Roomi, B. Gangapurkar, T. Kalinovsky, A. Niedzwiecki, M. Rath. (2007) Suppression of influenza A virus nuclear antigen production and neuraminidase activity by a nutrient mixture containing ascorbic acid, green tea extract and amino acids. BioFactors 31:1, 1-15
     CrossRef

174. 174

     S. Bouvresse, F. Bricaire, P. Bossi. (2007) Influenza. EMC - AKOS - Trattato di Medicina 9:3, 1-8
     CrossRef

175. 175

     H. Gras-Masse, N. Willand. (2007) Les inhibiteurs de neuraminidase face au risque de grippe aviaire. Annales Pharmaceutiques Françaises 65:1, 50-57
     CrossRef

176. 176

     Salin Chutinimitkul, Kamol Suwannakarn, Thaweesak Chieochansin, Le Quynh Mai, Sudarat Damrongwatanapokin, Arunee Chaisingh, Alongkorn Amonsin, Olfert Landt, Thaweesak Songserm, Apiradee Theamboonlers, Yong Poovorawan. (2007) H5N1 Oseltamivir-resistance detection by real-time PCR using two high sensitivity labeled TaqMan probes. Journal of Virological Methods 139:1, 44-49
     CrossRef

177. 177

     Karen M. Bromfield, Henrik Gradén, Daniel P. Hagberg, Thomas Olsson, Nina Kann. (2007) An iron carbonyl approach to the influenza neuraminidase inhibitor oseltamivir. Chemical Communications:30, 3183
     CrossRef

178. 178

     John S. Oxford. (2007) Antivirals for the treatment and prevention of epidemic and pandemic influenza. Influenza and Other Respiratory Viruses 1:1, 27-34
     CrossRef

179. 179

     L. Kaiser. (2006) Influenza Will Not Miss Opportunities. Clinical Infectious Diseases 43:12, 1562-1564
     CrossRef

180. 180

     Mark R. Looney. (2006) Newly Recognized Causes of Acute Lung Injury: Transfusion of Blood Products, Severe Acute Respiratory Syndrome, and Avian Influenza. Clinics in Chest Medicine 27:4, 591-600
     CrossRef

181. 181

     Erik De Clercq. (2006) Antiviral agents active against influenza A viruses. Nature Reviews Drug Discovery 5:12, 1015-1025
     CrossRef

182. 182

     Zhangyong Hong, Lei Liu, Che-Chang Hsu, Chi-Huey Wong. (2006) Three-Step Synthesis of Sialic Acids and Derivatives. Angewandte Chemie International Edition 45:44, 7417-7421
     CrossRef

183. 183

     Zhangyong Hong, Lei Liu, Che-Chang Hsu, Chi-Huey Wong. (2006) Three-Step Synthesis of Sialic Acids and Derivatives. Angewandte Chemie 118:44, 7577-7581
     CrossRef

184. 184

     Aeron C Hurt, Hui-Ting Ho, Ian Barr. (2006) Resistance to anti-influenza drugs: adamantanes and neuraminidase inhibitors. Expert Review of Anti-infective Therapy 4:5, 795-805
     CrossRef

185. 185

     Alan W Hampson. (2006) Avian influenza: A pandemic waiting in the wings?. Emergency Medicine Australasia 18:5-6, 420-429
     CrossRef

186. 186

     Frederick G. Hayden. (2006) Antivirals for influenza: Historical perspectives and lessons learned. Antiviral Research 71:2-3, 372-378
     CrossRef

187. 187

     Kenneth W. Tsang, Young-Soo Shim, Thomas K. S. Wong, C. K. Liam, Philip Eng, W. K. Lam, W. H. Seto. (2006) Possible case scenarios and logistic issues in H5N1 pandemic. Respirology 11:5, 520-522
     CrossRef

188. 188

     Graeme Laver. (2006) Antiviral drugs for influenza: Tamiflu ^® past, present and future. Future Virology 1:5, 577-586
     CrossRef

189. 189

     D. Kumar, A. Humar. (2006) Pandemic Influenza and Its Implications for Transplantation.. American Journal of Transplantation 6:7, 1512-1517
     CrossRef

190. 190

     Robert J. Snelgrove, Lorna Edwards, Aaron J. Rae, Tracy Hussell. (2006) An absence of reactive oxygen species improves the resolution of lung influenza infection. European Journal of Immunology 36:6, 1364-1373
     CrossRef

191. 191

     Peter C Doherty, Stephen J Turner, Richard G Webby, Paul G Thomas. (2006) Influenza and the challenge for immunology. Nature Immunology 7:5, 449-455
     CrossRef

192. 192

     Frederick G Hayden. (2006) Respiratory viral threats. Current Opinion in Infectious Diseases 19:2, 169-178
     CrossRef

193. 193

     Jan-Inge Henter, Chun-Bong Chow, Chi-Wai Leung, Yu-Lung Lau. (2006) Cytotoxic therapy for severe avian influenza A (H5N1) infection. The Lancet 367:9513, 870-873
     CrossRef

194. 194

     Regina Allwinn, Domenica Varwig, Hans Wilhelm Doerr. (2006) Vogelgrippe aktuell: Auslöser einer neuen Pandemie? Avian influenza updated: will it trigger the next pandemic?. LaboratoriumsMedizin 30:1, 23-25
     CrossRef

195. 195

     Stephen M Ford, John D Grabenstein. (2006) Pandemics, Avian Influenza A (H5N1), and a Strategy for Pharmacists. Pharmacotherapy 26:3, 312-322
     CrossRef

196. 196

     (2006) Vogelgrippe (Geflügelpest) und mögliche InfluenzapandemieKommission für Infektionskrankheiten und Impffragen der DAKJ, Mitglieder: P. Bartmann, U. Heininger (Vorsitzender), H.I. Huppertz, R. Klein, M. Kinet, G.Ch. Korenke. Monatsschrift Kinderheilkunde 154:2, 174-178
     CrossRef

197. 197

     Keiko MITAMURA, Norio SUGAYA. (2006) Diagnosis and Treatment of influenza. Uirusu 56:1, 109-116
     CrossRef

198. 198

     P. L. B. Bruijnzeel. (2006) Neuraminidaseremmers voor de behandeling van influenza. Medisch-Farmaceutische Mededelingen 44:1, 26-27
     CrossRef

199. 199

     Moon-Hyun Chung. (2006) New Antimicrobial Agents in Respiratory Medicine. Tuberculosis and Respiratory Diseases 60:1, 5
     CrossRef

200. 200

     de Jong, Menno D., Thanh, Tran Tan, Khanh, Truong Huu, Hien, Vo Minh, Smith, Gavin J.D., Chau, Nguyen Vinh, Cam, Bach Van, Qui, Phan Tu, Ha, Do Quang, Guan, Yi, Peiris, J.S. Malik, Hien, Tran Tinh, Farrar, Jeremy, . (2005) Oseltamivir Resistance during Treatment of Influenza A (H5N1) Infection. New England Journal of Medicine 353:25, 2667-2672
     Full Text

201. 201

     Moscona, Anne, . (2005) Oseltamivir Resistance — Disabling Our Influenza Defenses. New England Journal of Medicine 353:25, 2633-2636
     Full Text

202. 202

     &NA;. (2005) Oseltamivir, zanamivir leading the charge against influenza H5N1. Inpharma Weekly &NA;:1508, 3
     CrossRef