TY - JOUR T1 - Vitamin C inhibits SARS coronavirus-2 main protease essential for viral replication JF - bioRxiv DO - 10.1101/2021.05.02.442358 SP - 2021.05.02.442358 AU - Tek Narsingh Malla AU - Suraj Pandey AU - Ishwor Poudyal AU - Luis Aldama AU - Dennis Feliz AU - Moraima Noda AU - George N. Phillips, Jr. AU - Emina A. Stojković AU - Marius Schmidt Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/03/2021.05.02.442358.abstract N2 - There 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. We also demonstrate that L-ascorbate inhibits the 3CLpro in vitro at mmol/L concentrations. 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. Since ascorbate is readily available, as an over-the-counter vitamin supplement, our results have the potential for development of a global and inexpensive antiviral treatment.Competing Interest StatementThe authors have declared no competing interest. ER -