In Silico Analysis of the Multi-Targeted Mode of Action of Ivermectin and Related Compounds

{ 'indexed': {'date-parts': [[2022, 3, 26]], 'date-time': '2022-03-26T12:43:21Z', 'timestamp': 1648298601316}, 'reference-count': 0, 'publisher': 'MDPI AG', 'issue': '4', 'license': [ { 'start': { 'date-parts': [[2022, 3, 25]], 'date-time': '2022-03-25T00:00:00Z', 'timestamp': 1648166400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'short-container-title': ['Computation'], 'abstract': '<jats:p>Some clinical studies have indicated activity of ivermectin, a macrocyclic lactone, ' 'against COVID-19, but a biological mechanism initially proposed for this anti-viral effect is ' 'not applicable at physiological concentrations. This in silico investigation explores ' 'potential modes of action of ivermectin and 14 related compounds, by which the infectivity ' 'and morbidity of the SARS-CoV-2 virus may be limited. Binding affinity computations were ' 'performed for these agents on several docking sites each for models of (1) the spike ' 'glycoprotein of the virus, (2) the CD147 receptor, which has been identified as a secondary ' 'attachment point for the virus, and (3) the alpha-7 nicotinic acetylcholine receptor ' '(α7nAChr), an indicated point of viral penetration of neuronal tissue as well as an ' 'activation site for the cholinergic anti-inflammatory pathway controlled by the vagus nerve. ' 'Binding affinities were calculated for these multiple docking sites and binding modes of each ' 'compound. Our results indicate the high affinity of ivermectin, and even higher affinities ' 'for some of the other compounds evaluated, for all three of these molecular targets. These ' 'results suggest biological mechanisms by which ivermectin may limit the infectivity and ' 'morbidity of the SARS-CoV-2 virus and stimulate an α7nAChr-mediated anti-inflammatory pathway ' 'that could limit cytokine production by immune cells.</jats:p>', 'DOI': '10.3390/computation10040051', 'type': 'journal-article', 'created': {'date-parts': [[2022, 3, 25]], 'date-time': '2022-03-25T19:31:21Z', 'timestamp': 1648236681000}, 'page': '51', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': ['In Silico Analysis of the Multi-Targeted Mode of Action of Ivermectin and Related Compounds'], 'prefix': '10.3390', 'volume': '10', 'author': [ {'given': 'Maral', 'family': 'Aminpour', 'sequence': 'first', 'affiliation': []}, {'given': 'Marco', 'family': 'Cannariato', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jordane', 'family': 'Preto', 'sequence': 'additional', 'affiliation': []}, {'given': 'M. Ehsan', 'family': 'Safaeeardebili', 'sequence': 'additional', 'affiliation': []}, {'given': 'Alexia', 'family': 'Moracchiato', 'sequence': 'additional', 'affiliation': []}, {'given': 'Domiziano', 'family': 'Doria', 'sequence': 'additional', 'affiliation': []}, {'given': 'Francesca', 'family': 'Donato', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-6690-5986', 'authenticated-orcid': False, 'given': 'Eric Adriano', 'family': 'Zizzi', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-1918-1772', 'authenticated-orcid': False, 'given': 'Marco Agostino', 'family': 'Deriu', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-6841-7054', 'authenticated-orcid': False, 'given': 'David E.', 'family': 'Scheim', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-4724-9738', 'authenticated-orcid': False, 'given': 'Alessandro D.', 'family': 'Santin', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-9976-0429', 'authenticated-orcid': False, 'given': 'Jack Adam', 'family': 'Tuszynski', 'sequence': 'additional', 'affiliation': []}], 'member': '1968', 'published-online': {'date-parts': [[2022, 3, 25]]}, 'container-title': ['Computation'], 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.mdpi.com/2079-3197/10/4/51/pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 3, 25]], 'date-time': '2022-03-25T20:06:29Z', 'timestamp': 1648238789000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.mdpi.com/2079-3197/10/4/51'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 3, 25]]}, 'references-count': 0, 'journal-issue': {'issue': '4', 'published-online': {'date-parts': [[2022, 4]]}}, 'alternative-id': ['computation10040051'], 'URL': 'http://dx.doi.org/10.3390/computation10040051', 'relation': {}, 'ISSN': ['2079-3197'], 'issn-type': [{'value': '2079-3197', 'type': 'electronic'}], 'subject': [ 'Applied Mathematics', 'Modeling and Simulation', 'General Computer Science', 'Theoretical Computer Science'], 'published': {'date-parts': [[2022, 3, 25]]}}