Enisamium Inhibits SARS-CoV-2 RNA Synthesis


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Authors
Bojkova, Denisa 
Bechtel, Marco 
Vial, Thomas 
Boltz, David 
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.

Description
Keywords
COVID-19, SARS-CoV-2, molecular dynamics simulation, RNA polymerase, FAV00A, Amizon
Journal Title
Biomedicines
Conference Name
Journal ISSN
2227-9059
Volume Title
9
Publisher
MDPI
Sponsorship
Wellcome (206579/Z/17/Z)
ZonMw (10430 01 201 0018)