|Title||Enisamium Inhibits SARS-CoV-2 RNA Synthesis.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Elli, S, Bojkova, D, Bechtel, M, Vial, T, Boltz, D, Muzzio, M, Peng, X, Sala, F, Cosentino, C, Goy, A, Guerrini, M, Müller, L, Cinatl, J, Margitich, V, Velthuis, AJWTe|
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.
|PubMed Central ID||PMC8467925|
|Grant List||206579/Z/17/Z / / Wellcome / |
10430 01 201 0018 / ZONMW_ / ZonMw / Netherlands