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Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture

View ORCID ProfileKenneth H. Risner, View ORCID ProfileKatie V. Tieu, View ORCID ProfileYafei Wang, View ORCID ProfileMichael Getz, View ORCID ProfileAllison Bakovic, View ORCID ProfileNishank Bhalla, View ORCID ProfileSteven D. Nathan, View ORCID ProfileDaniel E. Conway, View ORCID ProfilePaul Macklin, View ORCID ProfileAarthi Narayanan, Farhang Alem
doi: https://doi.org/10.1101/2020.08.12.246389
Kenneth H. Risner
1Center for Infectious Disease Research, George Mason University, Manassas, Virginia, United States of America
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Katie V. Tieu
2Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia, United States of America
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Yafei Wang
3Intellegent Systems Engineering, Indiana University, Bloomington, Indiana, United States of America
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Michael Getz
3Intellegent Systems Engineering, Indiana University, Bloomington, Indiana, United States of America
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Allison Bakovic
1Center for Infectious Disease Research, George Mason University, Manassas, Virginia, United States of America
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Nishank Bhalla
1Center for Infectious Disease Research, George Mason University, Manassas, Virginia, United States of America
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Steven D. Nathan
4Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Fairfax, Virginia, United States of America
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Daniel E. Conway
2Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia, United States of America
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Paul Macklin
3Intellegent Systems Engineering, Indiana University, Bloomington, Indiana, United States of America
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Aarthi Narayanan
1Center for Infectious Disease Research, George Mason University, Manassas, Virginia, United States of America
5American Type Culture Collection, Manassas, Virginia, United States of America
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  • For correspondence: anaraya1@gmu.edu
Farhang Alem
1Center for Infectious Disease Research, George Mason University, Manassas, Virginia, United States of America
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Abstract

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 investigation into 18 small molecules and 3 biologics was conducted in cell culture and the impact of treatment on viral titer was quantified by plaque assay. The investigation 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 the context of drugtreatment. 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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • This include improved analyses of experiments, better contextualization, refined simulation results, and updated discussion.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 09, 2022.
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Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture
Kenneth H. Risner, Katie V. Tieu, Yafei Wang, Michael Getz, Allison Bakovic, Nishank Bhalla, Steven D. Nathan, Daniel E. Conway, Paul Macklin, Aarthi Narayanan, Farhang Alem
bioRxiv 2020.08.12.246389; doi: https://doi.org/10.1101/2020.08.12.246389
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Maraviroc inhibits SARS-CoV-2 multiplication and s-protein mediated cell fusion in cell culture
Kenneth H. Risner, Katie V. Tieu, Yafei Wang, Michael Getz, Allison Bakovic, Nishank Bhalla, Steven D. Nathan, Daniel E. Conway, Paul Macklin, Aarthi Narayanan, Farhang Alem
bioRxiv 2020.08.12.246389; doi: https://doi.org/10.1101/2020.08.12.246389

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