Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called coronavirus disease 2019 (COVID-19). While control of the SARS-CoV-2 spread partly depends on vaccine-induced or naturally acquired protective herd immunity, antiviral strategies are still needed to manage COVID-19. Enisamium is an inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. In vitro, enisamium acts through metabolite VR17-04 and inhibits the activity of the influenza A virus RNA polymerase. Here we show that enisamium can inhibit coronavirus infections in NHBE and Caco-2 cells, and the activity of the SARS-CoV-2 RNA polymerase in vitro. Docking and molecular dynamics simulations provide insight into the mechanism of action and indicate that enisamium metabolite VR17-04 prevents GTP and UTP incorporation. Overall, these results suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis in vitro.
【저자키워드】 COVID-19, SARS-CoV-2, Molecular dynamics simulation, RNA polymerase, FAV00A, Amizon, 【초록키워드】 coronavirus disease, Coronavirus infection, Immunity, influenza A virus, in vitro, virus, influenza A, Spread, Cell culture, Mild, SARS-CoV-2 RNA, inhibitor, mechanism of action, antiviral strategy, metabolite, Protective, Caco-2 cells, severe respiratory disease, NHBE, while, country, Prevent, Commonwealth, clinically, inhibit, approved, cause, GTP, the SARS-CoV-2, UTP, 【제목키워드】 SARS-CoV-2 RNA, synthesis,