RT Journal Article
SR Electronic
T1 Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.12.246389
DO 10.1101/2020.08.12.246389
A1 Kenneth H. Risner
A1 Katie V. Tieu
A1 Yafei Wang
A1 Allison Bakovic
A1 Farhang Alem
A1 Nishank Bhalla
A1 Steven Nathan
A1 Daniel E. Conway
A1 Paul Macklin
A1 Aarthi Narayanan
YR 2020
UL http://biorxiv.org/content/early/2020/08/13/2020.08.12.246389.abstract
AB In an effort to identify therapeutic intervention strategies for the treatment of COVID-19, we have investigated a selection of FDA-approved small molecules and biologics that are commonly used to treat other human diseases. A screen of 19 small molecules and 3 biologics was conducted in cell culture and the impact of treatment on viral titer was quantified by plaque assay. The screen identified 4 FDA-approved small molecules, Maraviroc, FTY720 (Fingolimod), Atorvastatin and Nitazoxanide that were able to inhibit SARS-CoV-2 infection. Confocal microscopy with over expressed S protein demonstrated that Maraviroc reduced the extent of S-protein mediated cell fusion as observed by fewer multinucleate cells in drug-treated cells. Mathematical modeling of drug-dependent viral multiplication dynamics revealed that prolonged drug treatment will exert an exponential decrease in viral load in a multicellular/tissue environment. Taken together, the data demonstrate that Maraviroc, Fingolimod, Atorvastatin and Nitazoxanide inhibit SARS-CoV-2 in cell culture.HighlightsMaraviroc, FTY720, Nitazoxanide and Atorvastatin inhibit SARS-CoV-2 multiplication in cell culture.Maraviroc does not interfere with the interaction between SARS-CoV-2 spike protein and ACE2 receptor.Maraviroc exhibits only modest synergistic activities with FTY720, Nitazoxanide or Atorvastatin.Maraviroc reduces the extent of SARS-CoV-2 S-protein mediated cell fusion.Mathematical modeling reveals that Maraviroc treatment will elicit an exponential decrease in viral load in a multicellular tissue environment.Competing Interest StatementThe authors have declared no competing interest.