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

Background: Drug resistance is a critical problem in health care that affects therapy outcomes and requires new approaches to drug design. SARS-CoV-2 Mpro mutations are of concern as they can potentially reduce therapeutic efficacy. Viral infections are amongst the many disorders for which nutraceut...

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Main Authors: Ivana Đukić, Nevena Kaličanin, Milan Sencanski, Snezana B. Pajovic, Jelena Milicevic, Jelena Prljic, Slobodan Paessler, Radivoje Prodanović, Sanja Glisic
Format: Article
Language:English
Published: IMR Press 2023-01-01
Series:Frontiers in Bioscience-Landmark
Subjects:
Online Access:https://www.imrpress.com/journal/FBL/28/1/10.31083/j.fbl2801008
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author Ivana Đukić
Nevena Kaličanin
Milan Sencanski
Snezana B. Pajovic
Jelena Milicevic
Jelena Prljic
Slobodan Paessler
Radivoje Prodanović
Sanja Glisic
author_facet Ivana Đukić
Nevena Kaličanin
Milan Sencanski
Snezana B. Pajovic
Jelena Milicevic
Jelena Prljic
Slobodan Paessler
Radivoje Prodanović
Sanja Glisic
author_sort Ivana Đukić
collection DOAJ
description Background: Drug resistance is a critical problem in health care that affects therapy outcomes and requires new approaches to drug design. SARS-CoV-2 Mpro 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 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: L-arginine was found to be active against SARS-CoV-2 Mpro, while a vitamin C/L-arginine combination had a synergistic antiviral action against Mpro. These findings confirm the results of our previous in silico repurposing study that showed L-arginine and vitamin C were potential Mpro 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.
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spelling doaj.art-bf2eb6013eb24f28b6e4b60f0def1ec72023-02-01T09:21:18ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-01-01281810.31083/j.fbl2801008S2768-6701(22)00744-4Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine CombinationIvana Đukić0Nevena Kaličanin1Milan Sencanski2Snezana B. Pajovic3Jelena Milicevic4Jelena Prljic5Slobodan Paessler6Radivoje Prodanović7Sanja Glisic8University of Belgrade-Faculty of Chemistry, 11000 Belgrade, SerbiaUniversity of Belgrade-Institute of Chemistry, Technology and Metallurgy, 11000 Belgrade, SerbiaLaboratory of Bioinformatics and Computational Chemistry, Institute of Nuclear Sciences Vinca, National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaDepartment of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaLaboratory of Bioinformatics and Computational Chemistry, Institute of Nuclear Sciences Vinca, National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaLaboratory of Bioinformatics and Computational Chemistry, Institute of Nuclear Sciences Vinca, National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaDepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USAUniversity of Belgrade-Faculty of Chemistry, 11000 Belgrade, SerbiaLaboratory of Bioinformatics and Computational Chemistry, Institute of Nuclear Sciences Vinca, National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaBackground: Drug resistance is a critical problem in health care that affects therapy outcomes and requires new approaches to drug design. SARS-CoV-2 Mpro 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 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: L-arginine was found to be active against SARS-CoV-2 Mpro, while a vitamin C/L-arginine combination had a synergistic antiviral action against Mpro. These findings confirm the results of our previous in silico repurposing study that showed L-arginine and vitamin C were potential Mpro 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.https://www.imrpress.com/journal/FBL/28/1/10.31083/j.fbl2801008anti sars-cov-2mprocovid-19argininevitamin c/arginine combinationmpro candidate inhibitors
spellingShingle Ivana Đukić
Nevena Kaličanin
Milan Sencanski
Snezana B. Pajovic
Jelena Milicevic
Jelena Prljic
Slobodan Paessler
Radivoje Prodanović
Sanja Glisic
Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination
Frontiers in Bioscience-Landmark
anti sars-cov-2
mpro
covid-19
arginine
vitamin c/arginine combination
mpro candidate inhibitors
title Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination
title_full Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination
title_fullStr Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination
title_full_unstemmed Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination
title_short Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination
title_sort inhibition of sars cov 2 mpro with vitamin c l arginine and a vitamin c l arginine combination
topic anti sars-cov-2
mpro
covid-19
arginine
vitamin c/arginine combination
mpro candidate inhibitors
url https://www.imrpress.com/journal/FBL/28/1/10.31083/j.fbl2801008
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