Abstract
It is more than 20 years since the neuraminidase inhibitors, oseltamivir and zanamivir were approved for the treatment and prevention of influenza. Guidelines for global surveillance and methods for evaluating resistance were established initially by the Neuraminidase Inhibitor Susceptibility Network (NISN), which merged 10 years ago with the International Society for influenza and other Respiratory Virus Diseases (isirv) to become the isirv-Antiviral Group (isirv-AVG). With the ongoing development of new influenza polymerase inhibitors and recent approval of baloxavir marboxil, the isirv-AVG held a closed meeting in August 2019 to discuss the impact of resistance to these inhibitors. Following this meeting and review of the current literature, this article is intended to summarize current knowledge regarding the clinical impact of resistance to polymerase inhibitors and approaches for surveillance and methods for laboratory evaluation of resistance, both in vitro and in animal models. We highlight limitations and gaps in current knowledge and suggest some strategies for addressing these gaps, including the need for additional clinical studies of influenza antiviral drug combinations. Lessons learned from influenza resistance monitoring may also be helpful for establishing future drug susceptibility surveillance and testing for SARS-CoV-2.
| Original language | English (US) |
|---|---|
| Article number | 105158 |
| Journal | Antiviral Research |
| Volume | 194 |
| DOIs | |
| State | Published - Oct 2021 |
Funding
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MI received research support, paid to Northwestern University, from AiCuris, GlaxoSmithKline, Janssen Inc. and Shire; he is a paid consultant for Adagio, AlloVir, Celltrion, Cidara, Genentech Inc., F. Hoffmann-La Roche Ltd, Janssen Inc., Shionogi Inc., Viracor Eurofins; he is also a paid member of DSMBs from CSL Behring, Janssen Inc., Merck, SAB Biotherapeutics, Sequiris and Takeda. LG No declarations. FGH : Personal honoraria from World Health Organization and University of Alabama Antiviral Drug Discovery and Development Consortium; charitable donations by Cidara, resTORbio, Shionogi for consulting; meeting travel costs provided by Shionogi and Roche; non-compensated consulting for Arcturus, FujiFilm/Toyama, Gilead, GSK, Janssen/JNJ, MedImmune, Merck, Regeneron, resTORbio, Ridgeback, Genentech, SAB Biotherapeutics, Vir, Visterra; Versatope, DSMB chair/member for studies by Celltrion, GSK, and Vaccitech with fees paid to the University of Virginia. AH No declarations. EG is supported with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contracts HHSN272201400006C and 75N93021C00016. ET No declarations. JMB No declarations. We gratefully acknowledge helpful discussions with the following:Wendy S. Barclay, Alicia M. Fry, Aeron C. Hurt, John W. McCauley, Nahako Shindo, Norio Sugaya, Reiko Saito, Maria Zambon, Mira C. Patel. EG is supported with Federal funds from the National Institute of Allergy and Infectious Diseases , National Institutes of Health , Department of Health and Human Services , under Contracts HHSN272201400006C and 75N93021C00016 .
Keywords
- Antiviral
- Baloxavir
- Drug resistance
- Fitness
- Influenza virus
- Polymerase inhibitor
ASJC Scopus subject areas
- Pharmacology
- Virology
