SARS-CoV-2 Main Protease Active Site Ligands in the Human Metabolome
In late 2019, a global pandemic occurred. The causative agent was identified as a member of the <i>Coronaviridae</i> family, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we present an analysis on the substances identified in the human metabolome cap...
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doaj-e40d040b5baf4dc9820bbb69dc96f81d2021-03-06T00:05:11ZengMDPI AGMolecules1420-30492021-03-01261409140910.3390/molecules26051409SARS-CoV-2 Main Protease Active Site Ligands in the Human MetabolomeAnna Maria Sardanelli0Camilla Isgrò1Luigi Leonardo Palese2Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, Piazza G. Cesare 11, 70124 Bari, ItalyDepartment of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, Piazza G. Cesare 11, 70124 Bari, ItalyDepartment of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, Piazza G. Cesare 11, 70124 Bari, ItalyIn late 2019, a global pandemic occurred. The causative agent was identified as a member of the <i>Coronaviridae</i> family, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we present an analysis on the substances identified in the human metabolome capable of binding the active site of the SARS-CoV-2 main protease (M<sup>pro</sup>). The substances present in the human metabolome have both endogenous and exogenous origins. The aim of this research was to find molecules whose biochemical and toxicological profile was known that could be the starting point for the development of antiviral therapies. Our analysis revealed numerous metabolites—including xenobiotics—that bind this protease, which are essential to the lifecycle of the virus. Among these substances, silybin, a flavolignan compound and the main active component of silymarin, is particularly noteworthy. Silymarin is a standardized extract of milk thistle, <i>Silybum marianum</i>, and has been shown to exhibit antioxidant, hepatoprotective, antineoplastic, and antiviral activities. Our results—obtained in silico and in vitro—prove that silybin and silymarin, respectively, are able to inhibit M<sup>pro</sup>, representing a possible food-derived natural compound that is useful as a therapeutic strategy against COVID-19.https://www.mdpi.com/1420-3049/26/5/1409coronavirusCOVID-19SARS-CoV-2M<sup>pro</sup>3C-like protease3CL protease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Maria Sardanelli Camilla Isgrò Luigi Leonardo Palese |
spellingShingle |
Anna Maria Sardanelli Camilla Isgrò Luigi Leonardo Palese SARS-CoV-2 Main Protease Active Site Ligands in the Human Metabolome Molecules coronavirus COVID-19 SARS-CoV-2 M<sup>pro</sup> 3C-like protease 3CL protease |
author_facet |
Anna Maria Sardanelli Camilla Isgrò Luigi Leonardo Palese |
author_sort |
Anna Maria Sardanelli |
title |
SARS-CoV-2 Main Protease Active Site Ligands in the Human Metabolome |
title_short |
SARS-CoV-2 Main Protease Active Site Ligands in the Human Metabolome |
title_full |
SARS-CoV-2 Main Protease Active Site Ligands in the Human Metabolome |
title_fullStr |
SARS-CoV-2 Main Protease Active Site Ligands in the Human Metabolome |
title_full_unstemmed |
SARS-CoV-2 Main Protease Active Site Ligands in the Human Metabolome |
title_sort |
sars-cov-2 main protease active site ligands in the human metabolome |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-03-01 |
description |
In late 2019, a global pandemic occurred. The causative agent was identified as a member of the <i>Coronaviridae</i> family, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we present an analysis on the substances identified in the human metabolome capable of binding the active site of the SARS-CoV-2 main protease (M<sup>pro</sup>). The substances present in the human metabolome have both endogenous and exogenous origins. The aim of this research was to find molecules whose biochemical and toxicological profile was known that could be the starting point for the development of antiviral therapies. Our analysis revealed numerous metabolites—including xenobiotics—that bind this protease, which are essential to the lifecycle of the virus. Among these substances, silybin, a flavolignan compound and the main active component of silymarin, is particularly noteworthy. Silymarin is a standardized extract of milk thistle, <i>Silybum marianum</i>, and has been shown to exhibit antioxidant, hepatoprotective, antineoplastic, and antiviral activities. Our results—obtained in silico and in vitro—prove that silybin and silymarin, respectively, are able to inhibit M<sup>pro</sup>, representing a possible food-derived natural compound that is useful as a therapeutic strategy against COVID-19. |
topic |
coronavirus COVID-19 SARS-CoV-2 M<sup>pro</sup> 3C-like protease 3CL protease |
url |
https://www.mdpi.com/1420-3049/26/5/1409 |
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