@article{188891, author = {Stefano Elli and Denisa Bojkova and Marco Bechtel and Thomas Vial and David Boltz and Miguel Muzzio and Xinjian Peng and Federico Sala and Cesare Cosentino and Andrew Goy and Marco Guerrini and Lutz M{\"u}ller and Jindrich Cinatl and Victor Margitich and Aartjan Te Velthuis}, title = {Enisamium Inhibits SARS-CoV-2 RNA Synthesis}, abstract = { 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. }, year = {2021}, journal = {Biomedicines}, volume = {9}, month = {09/2021}, issn = {2227-9059}, doi = {10.3390/biomedicines9091254}, language = {eng}, }