"The anti-HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor" by Farhana Musarrat, Vladimir Chouljenko et al.

Faculty Publications

Title

The anti-HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV-2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID-19 infections

Authors

Farhana Musarrat, Division of Biotechnology and Molecular Medicine, Louisiana State University, Baton Rouge, Louisiana.
Vladimir Chouljenko, Division of Biotechnology and Molecular Medicine, Louisiana State University, Baton Rouge, Louisiana.
Achyut Dahal, School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, Louisiana.
Rafiq Nabi, Division of Biotechnology and Molecular Medicine, Louisiana State University, Baton Rouge, Louisiana.
Tamara Chouljenko, Louisiana State University Agricultural Center, Agricultural Biotechnology Laboratory, Baton Rouge, Louisiana.
Seetharama D. Jois, School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, Louisiana.
Konstantin G. Kousoulas, Division of Biotechnology and Molecular Medicine, Louisiana State University, Baton Rouge, Louisiana.

Document Type

Article

Publication Date

10-1-2020

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is the causative agent of the coronavirus disease-2019 (COVID-19) pandemic. Coronaviruses enter cells via fusion of the viral envelope with the plasma membrane and/or via fusion of the viral envelope with endosomal membranes after virion endocytosis. The spike (S) glycoprotein is a major determinant of virus infectivity. Herein, we show that the transient expression of the SARS CoV-2 S glycoprotein in Vero cells caused extensive cell fusion (formation of syncytia) in comparison to limited cell fusion caused by the SARS S glycoprotein. Both S glycoproteins were detected intracellularly and on transfected Vero cell surfaces. These results are in agreement with published pathology observations of extensive syncytia formation in lung tissues of patients with COVID-19. These results suggest that SARS CoV-2 is able to spread from cell-to-cell much more efficiently than SARS effectively avoiding extracellular neutralizing antibodies. A systematic screening of several drugs including cardiac glycosides and kinase inhibitors and inhibitors of human immunodeficiency virus (HIV) entry revealed that only the FDA-approved HIV protease inhibitor, nelfinavir mesylate (Viracept) drastically inhibited S-n- and S-o-mediated cell fusion with complete inhibition at a 10-μM concentration. In-silico docking experiments suggested the possibility that nelfinavir may bind inside the S trimer structure, proximal to the S2 amino terminus directly inhibiting S-n- and S-o-mediated membrane fusion. Also, it is possible that nelfinavir may act to inhibit S proteolytic processing within cells. These results warrant further investigations of the potential of nelfinavir mesylate to inhibit virus spread at early times after SARS CoV-2 symptoms appear.

Publication Source (Journal or Book title)

Journal of medical virology

First Page

2087

Last Page

2095

Recommended Citation

Musarrat, F., Chouljenko, V., Dahal, A., Nabi, R., Chouljenko, T., Jois, S. D., & Kousoulas, K. G. (2020). The anti-HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV-2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID-19 infections. Journal of medical virology, 92 (10), 2087-2095. https://doi.org/10.1002/jmv.25985

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