Vitamin C Binds to SARS Coronavirus-2 Main Protease Essential for Viral Replication

By Tek Narsingh Malla1, Suraj Pandey1, Luis Aldama, Dennisse Feliz, Moraima Noda, Ishwor Poudyal1, George Phillips2, Emina Stojkovic3, Marius Schmidt1

1. University of Wisconsin - Milwaukee 2. Rice University 3. Northern Illinois University

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posted-content

Author

Tek Narsingh Malla and Suraj Pandey and Luis Aldama and Dennisse Feliz and Moraima Noda and Ishwor Poudyal and George N. Phillips and Emina A. Stojković and Marius Schmidt

Citation

Malla, T.N. et al., 2021. Vitamin C Binds to SARS Coronavirus-2 Main Protease Essential for Viral Replication. Available at: http://dx.doi.org/10.1101/2021.05.02.442358.

Abstract

AbstractThere is an urgent need for anti-viral agents that treat and/or prevent Covid-19 caused by SARS-Coronavirus (CoV-2) infections. The replication of the SARS CoV-2 is dependent on the activity of two cysteine proteases, a papain-like protease, PL-pro, and the 3C-like protease known as main protease Mpro or 3CLpro. The shortest and the safest path to clinical use is the repurposing of drugs with binding affinity to PLpro or 3CLpro that have an established safety profile in humans. Several studies have reported crystal structures of SARS-CoV-2 main protease in complex with FDA approved drugs such as those used in treatment of hepatitis C. Here, we report the crystal structure of 3CLpro in complex Vitamin C (L-ascorbate) bound to the protein’s active site at 2.5 Ångstrom resolution. The crystal structure of the Vitamin C 3CLpro complex may aid future studies on the effect of Vitamin C not only on the coronavirus main protease but on related proteases of other infectious viruses.

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