Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination

Abstract

Drug resistance is a critical problem in health care that affects therapy outcomes and requires new approaches to drugdesign. SARS-CoV-2 Mpro mutations are of concern as they can potentially reduce therapeutic efficacy. Viral infections are amongst themany disorders for which nutraceuticals have been employed as an adjunct therapy. The aim of this study was to examine the potentialin vitro activity of L-arginine and vitamin C against SARS-CoV-2 Mpro. Methods: The Mpro inhibition assay was developed by cloning,expression, purification, and characterization of Mpro. Selected compounds were then screened for protease inhibition. Results: Largininewas found to be active against SARS-CoV-2 Mpro, while a vitamin C/L-arginine combination had a synergistic antiviral actionagainst Mpro. These findings confirm the results of our previous in silico repurposing study that showed L-arginine and vitamin C werepotential Mpro inhibitors. Moreover, they suggest a possible molecular mechanism to explain the beneficial effect of arginine in COVIDpatients. Conclusions: The findings of the current study are important because they help to identify COVID-19 treatments that areefficient, inexpensive, and have a favorable safety profile. The results of this study also suggest a possible adjuvant nutritional strategyfor COVID-19 that could be used in conjunction with pharmacological agents.