In silico study of alkaloids with quercetin nucleus for inhibition of SARS-CoV-2 protease and receptor cell protease

{ 'indexed': {'date-parts': [[2024, 4, 17]], 'date-time': '2024-04-17T00:45:27Z', 'timestamp': 1713314727239}, 'reference-count': 55, 'publisher': 'Public Library of Science (PLoS)', 'issue': '4', 'license': [ { 'start': { 'date-parts': [[2024, 4, 16]], 'date-time': '2024-04-16T00:00:00Z', 'timestamp': 1713225600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['www.plosone.org'], 'crossmark-restriction': False}, 'abstract': '<jats:p>Covid-19 disease caused by the deadly SARS-CoV-2 virus is a serious and threatening ' 'global health issue declared by the WHO as an epidemic. Researchers are studying the design ' 'and discovery of drugs to inhibit the SARS-CoV-2 virus due to its high mortality rate. The ' 'main Covid-19 virus protease (Mpro) and human transmembrane protease, serine 2 (TMPRSS2) are ' 'attractive targets for the study of antiviral drugs against SARS-2 coronavirus. Increasing ' 'consumption of herbal medicines in the community and a serious approach to these drugs have ' 'increased the demand for effective herbal substances. Alkaloids are one of the most important ' 'active ingredients in medicinal plants that have wide applications in the pharmaceutical ' 'industry. In this study, seven alkaloid ligands with Quercetin nucleus for the inhibition of ' 'Mpro and TMPRSS2 were studied using computational drug design including molecular docking and ' 'molecular dynamics simulation (MD). Auto Dock software was used to evaluate molecular binding ' 'energy. Three ligands with the most negative docking score were selected to be entered into ' 'the MD simulation procedure. To evaluate the protein conformational changes induced by tested ' 'ligands and calculate the binding energy between the ligands and target proteins, GROMACS ' 'software based on AMBER03 force field was used. The MD results showed that Phyllospadine and ' 'Dracocephin-A form stable complexes with Mpro and TMPRSS2. Prolinalin-A indicated an ' 'acceptable inhibitory effect on Mpro, whereas it resulted in some structural instability of ' 'TMPRSS2. The total binding energies between three ligands, Prolinalin-A, Phyllospadine and ' 'Dracocephin-A and two proteins MPro and TMRPSS2 are (-111.235 ± 15.877, - 75.422 ± 11.140), ' '(-107.033 ± 9.072, -84.939 ± 10.155) and (-102.941 ± 9.477, - 92.451 ± 10.539), respectively. ' 'Since the binding energies are at a minimum, this indicates confirmation of the proper ' 'binding of the ligands to the proteins. Regardless of some Prolinalin-A-induced TMPRSS2 ' 'conformational changes, it may properly bind to TMPRSS2 binding site due to its acceptable ' 'binding energy. Therefore, these three ligands can be promising candidates for the ' 'development of drugs to treat infections caused by the SARS-CoV-2 virus.</jats:p>', 'DOI': '10.1371/journal.pone.0298201', 'type': 'journal-article', 'created': {'date-parts': [[2024, 4, 16]], 'date-time': '2024-04-16T17:57:25Z', 'timestamp': 1713290245000}, 'page': 'e0298201', 'update-policy': 'http://dx.doi.org/10.1371/journal.pone.corrections_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'In silico study of alkaloids with quercetin nucleus for inhibition of SARS-CoV-2 protease and ' 'receptor cell protease', 'prefix': '10.1371', 'volume': '19', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-2303-7231', 'authenticated-orcid': True, 'given': 'Ali', 'family': 'Mohebbi', 'sequence': 'first', 'affiliation': []}, {'given': 'Marzieh', 'family': 'Eskandarzadeh', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hanieh', 'family': 'Zangi', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-9687-2182', 'authenticated-orcid': True, 'given': 'Marzie', 'family': 'Fatehi', 'sequence': 'additional', 'affiliation': []}], 'member': '340', 'published-online': {'date-parts': [[2024, 4, 16]]}, 'reference': [ { 'key': 'pone.0298201.ref001', 'first-page': '1', 'volume-title': 'Coronaviruses: An Overview of Their Replication and Pathogenesis (Book ' 'Chapter), Coronaviruses: Methods and Protocols', 'author': 'A.R. 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