PT - JOURNAL ARTICLE AU - Tek Narsingh Malla AU - Suraj Pandey AU - Luis Aldama AU - Dennisse Feliz AU - Moraima Noda AU - Ishwor Poudyal AU - George N. Phillips, Jr. AU - Emina A. Stojković AU - Marius Schmidt TI - Vitamin C Binds to SARS Coronavirus-2 Main Protease Essential for Viral Replication AID - 10.1101/2021.05.02.442358 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.05.02.442358 4099 - http://biorxiv.org/content/early/2021/05/20/2021.05.02.442358.short 4100 - http://biorxiv.org/content/early/2021/05/20/2021.05.02.442358.full AB - 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. 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.Competing Interest StatementThe authors have declared no competing interest.