Influenza polymerase inhibitor resistance: Assessment of the current state of the art - A report of the isirv Antiviral group.

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.

Probing antiviral drugs against SARS-CoV-2 through virus-drug association prediction based on the KATZ method.

It is urgent to find an effective antiviral drug against SARS-CoV-2. In this study, 96 virus-drug associations (VDAs) from 12 viruses including SARS-CoV-2 and similar viruses and 78 small molecules are selected. Complete genomic sequence similarity of viruses and chemical structure similarity of drugs are then computed. A KATZ-based VDA prediction method (VDA-KATZ) is developed to infer possible drugs associated with SARS-CoV-2. VDA-KATZ obtained the best AUCs of 0.8803 when the walking length is 2. The predicted top 3 antiviral drugs against SARS-CoV-2 are remdesivir, oseltamivir, and zanamivir. Molecular docking is conducted between the predicted top 10 drugs and the virus spike protein/human ACE2. The results showed that the above 3 chemical agents have higher molecular binding energies with ACE2. For the first time, we found that zidovudine may be effective clues of treatment of COVID-19. We hope that our predicted drugs could help to prevent the spreading of COVID.