Summary
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.
Highlights
Maraviroc, 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 Statement
The authors have declared no competing interest.
