Special Issue "Antivirals Against Influenza"

Guest Editor
Dr. Megan Shaw
Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA
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Title: Animal models for influenza virus pathogenesis and transmission
Authors: Anice Lowen and Nicole Bouvier; E-Mail: anice.lowen@mssm.edu
Abstract: Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus infections, not all strains that can infect humans are able to transmit from person-to-person. Animal models of influenza are essential to research efforts aimed at understanding the viral and host factors which contribute to the disease and transmission outcomes of influenza virus infection in humans. These models furthermore allow the pre-clinical testing of antiviral drugs and vaccines aimed at reducing morbidity and mortality in the population through amelioration of the virulence or transmissibility of influenza viruses. Mice, ferrets, guinea pigs, cotton rats, hamsters and macaques have all been used to study influenza viruses and therapeutics targeting them. Each model presents unique advantages and disadvantages, which will be discussed herein.

Type of Paper: Review
Title: Combination Chemotherapy for Influenza
Authors: Elena A. Govorkova and Robert G. Webster; E-Mail: Elena.Govorkova@STJUDE.ORG
Abstract: Emergence of pandemic influenza H1N1 viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses emphasize the urgency for novel approaches for chemotherapy of influenza infections in humans. Currently anti-influenza drugs are limited to the neuraminidase (NA) inhibitors (oseltamivir and zanamivir) and to M2 ion channel blockers (amantadine and rimantadine), although the use of the latter class is compounded by the rapid development of drug resistance. A number of potential targets that could be exploited in the development of new anti-influenza agents include the viral polymerase (and endonuclease), the hemagglutinin, and the non-structural protein NS1. Due to the limitations of monotherapy and emergence of drug-resistant variants combination chemotherapy is the logical and attractive option. Here, we discuss the experimental data on combination chemotherapy with currently available agents and the development of new strategies directed at exploring drugs that are associated with virus-induced tissue damage and host responses.

Type of Paper: Review
Title: Refining Criteria for Neuraminidase Inhibitor Resistance in Human Influenza Viruses: a Surveillance Perspective
Authors: Okomo-Adhiambo, M., Sleeman, K., Ballenger, K., Smagala, J., Klimov, A.I. and Gubareva, L.V.
Affiliation: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA; E-Mail: lqg3@cdc.gov
Abstract: Neuraminidase inhibitors (NAIs) are vital in the management of seasonal and pandemic influenza infections. Resistance to NAIs, acquired or natural, is a major public health concern. Susceptibility of virus isolates to NAIs is currently assessed in the NA inhibition assay. The resulting data is analyzed using a curve-fitting software which generates IC₅₀ values. However, elevated IC₅₀ values alone are not sufficient criteria for defining NAI resistance, and should be combined with detection of molecular markers of resistance, preferably, in matching clinical specimens. The criteria for NAI-resistance are not well established and vary by laboratory and/or assay, and need to be harmonized to improve surveillance of NAI susceptibility.