http://www.mdpi.com/journal/viruses/special_issues/antivirals-influenza/ Dear Colleagues, Influenza continues to be a major health problem worldwide due to the constant mutation of circulating viruses and the possible emergence of a new influenza virus. This was emphasized by the declaration of an influenza pandemic in 2009 following the introduction of a novel H1N1 virus into the human population. For both seasonal and pandemic influenza, the availability of effective influenza antiviral drugs is critical for both therapeutic and prophylactic use. There are currently two classes of FDA-approved drugs for treating influenza infections. These are the neuraminidase inhibitors (oseltamivir, zanamivir and peramivir) and the M2 ion channel inhibitors (amantadine and rimantadine). Widespread resistance to the M2 inhibitors, caused by mutations in the M2 protein, has reduced their effectiveness and consequently neuraminidase inhibitors are usually the recommended therapy. However, rapid emergence of oseltamivir resistance amongst the seasonal H1N1 viruses has given cause for concern and clearly indicates that new drugs and/or new approaches are urgently required. In this special issue on “Antivirals Against Influenza”, the authors provide perspective on recent studies that address resistance to the current antivirals, options for combination therapies, new antiviral candidates in development and the availability of suitable animal models for ascertaining efficacy. Dr. Megan Shaw Guest Editor Submission All manuscripts should be submitted to viruses@mdpi.com with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website. Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed Open Access monthly journal published by MDPI. Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues, to be published in 2009 and 2010, the Article Processing Charges (APC) in this Open Access journal will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections. http://www.mdpi.com/1999-4915/3/8/1415/ The authors would like to make the following corrections to their published paper: There was an error in calculation of IC50 fold changes for the NAI-resistant viruses reported in Table 1 of the above-mentioned paper. The corrected values are marked in the updated Table 1 below. http://www.mdpi.com/1999-4915/3/8/1415/ Fri, 12 Aug 2011 00:00:00 CEST Viruses 2011-08-12 3 8 Correction 1415 1416 1999-4915 Correction: Okomo-Adhiambo, M. et al. Neuraminidase Inhibitor Susceptibility Testing in Human Influenza Viruses: A Laboratory Surveillance Perspective. Viruses 2010, 2, 2269-2289 2011-08-12 doi: 10.3390/v3081415 Margaret Okomo-Adhiambo Katrina Sleeman Kristina Ballenger Ha T. Nguyen Vasiliy P. Mishin Tiffany G. Sheu James Smagala Yan Li Alexander I. Klimov Larisa V. Gubareva http://www.mdpi.com/1999-4915/2/10/2269/ Neuraminidase inhibitors (NAIs) are vital in managing seasonal and pandemic influenza infections. NAI susceptibilities of virus isolates (n = 5540) collected during the 2008–2009 influenza season were assessed in the chemiluminescent neuraminidase inhibition (NI) assay. Box-and-whisker plot analyses of log-transformed IC50s were performed for each virus type/subtype and NAI to identify outliers which were characterized based on a statistical cutoff of IC50 >3 interquartile ranges (IQR) from the 75th percentile. Among 1533 seasonal H1N1 viruses tested, 1431 (93.3%) were outliers for oseltamivir; they all harbored the H275Y mutation in the neuraminidase (NA) and were reported as oseltamivir-resistant. Only 15 (0.7%) of pandemic 2009 H1N1 viruses tested (n = 2259) were resistant to oseltamivir. All influenza A(H3N2) (n = 834) and B (n = 914) viruses were sensitive to oseltamivir, except for one A(H3N2) and one B virus, with D151V and D197E (D198E in N2 numbering) mutations in the NA, respectively. All viruses tested were sensitive to zanamivir, except for six seasonal A(H1N1) and several A(H3N2) outliers (n = 22) which exhibited cell culture induced mutations at residue D151 of the NA. A subset of viruses (n = 1058) tested for peramivir were sensitive to the drug, with exception of H275Y variants that exhibited reduced susceptibility to this NAI. This study summarizes baseline susceptibility patterns of seasonal and pandemic influenza viruses, and seeks to contribute towards criteria for defining NAI resistance. http://www.mdpi.com/1999-4915/2/10/2269/ Wed, 13 Oct 2010 00:00:00 CEST Viruses 2010-10-13 2 10 Article 2269 2289 1999-4915 Neuraminidase Inhibitor Susceptibility Testing in Human Influenza Viruses: A Laboratory Surveillance Perspective 2010-10-13 doi: 10.3390/v2102269 Margaret Okomo-Adhiambo Katrina Sleeman Kristina Ballenger Ha T. Nguyen Vasiliy P. Mishin Tiffany G. Sheu James Smagala Yan Li Alexander I. Klimov Larisa V. Gubareva http://www.mdpi.com/1999-4915/2/8/1766/ While vaccines are the primary public health response to seasonal and pandemic flu, short of a universal vaccine there are inherent limitations to this approach. Antiviral drugs provide valuable alternative options for treatment and prophylaxis of influenza. Here, we will review drugs and drug candidates against influenza with an emphasis on the recent progress of a host-targeting entry-blocker drug candidate, DAS181, a sialidase fusion protein. http://www.mdpi.com/1999-4915/2/8/1766/ Fri, 20 Aug 2010 00:00:00 CEST Viruses 2010-08-20 2 8 Review 1766 1781 1999-4915 Antiviral Strategies for Pandemic and Seasonal Influenza 2010-08-20 doi: 10.3390/v2081766 Maria Hedlund Jeffrey L. Larson Fang Fang http://www.mdpi.com/1999-4915/2/8/1530/ 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 that 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. http://www.mdpi.com/1999-4915/2/8/1530/ Tue, 27 Jul 2010 00:00:00 CEST Viruses 2010-07-27 2 8 Review 1530 1563 1999-4915 Animal Models for Influenza Virus Pathogenesis and Transmission 2010-07-27 doi: 10.3390/v20801530 Nicole M. Bouvier Anice C. Lowen http://www.mdpi.com/1999-4915/2/8/1510/ The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir) and to M2 ion channel blockers (amantadine and rimantadine), although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease), the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets. http://www.mdpi.com/1999-4915/2/8/1510/ Tue, 27 Jul 2010 00:00:00 CEST Viruses 2010-07-27 2 8 Review 1510 1529 1999-4915 Combination Chemotherapy for Influenza 2010-07-27 doi: 10.3390/v2081510 Elena A. Govorkova Robert G. Webster http://www.mdpi.com/1999-4915/2/7/1448/ Influenza virus is one of the most prevalent and ancient infections in humans. About a fifth of world\'s population is infected by influenza virus annually, leading to high morbidity and mortality, particularly in infants, the elderly and the immunocompromised. In the US alone, influenza outbreaks lead to roughly 30,000 deaths each year. Current vaccines and anti-influenza drugs are of limited use due to high mutation rate of the virus and side effects. In recent years, RNA interference, triggered by synthetic short interfering RNA (siRNA), has rapidly evolved as a potent antiviral regimen. Properly designed siRNAs have been shown to function as potent inhibitors of influenza virus replication. The siRNAs outperform traditional small molecule antivirals in a number of areas, such as ease of design, modest cost, and fast turnaround. Although specificity and tissue delivery remain major bottlenecks in the clinical applications of RNAi in general, intranasal application of siRNA against respiratory viruses including, but not limited to influenza virus, has experienced significant success and optimism, which is reviewed here. http://www.mdpi.com/1999-4915/2/7/1448/ Fri, 09 Jul 2010 00:00:00 CEST Viruses 2010-07-09 2 7 Review 1448 1457 1999-4915 siRNA for Influenza Therapy 2010-07-09 doi: 10.3390/v2071448 Barik