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

Abstract

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

Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial

“…Oral l -arginine supplementation reduced the need for oxygen therapy and the length of hospital stay in patients with severe COVID-19 [ 23 ]. The combination of l -arginine plus vitamin C, which may support NOS activity in endothelial cells [ 24 ], showed a synergistic antiviral action on SARS-CoV-2 in vitro by inhibiting its main protease M pro [ 25 ]. A supplement containing l -arginine and vitamin C relieved the burden of persistent symptoms and improved perceived exertion in a large cohort of adults with long COVID [ 26 ].…”