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Antimicrobial Alkaloids from Marine-Derived Fungi as Drug Leads versus COVID-19 Infection: A Computational Approach to Explore their Anti-COVID-19 Activity and ADMET Properties
Therapeutic strategies based upon enzyme inhibition have recently gained higher attention in treating hazardous ailments. Herein, the potential use of seventy-two antimicrobial alkaloids isolated from marine-derived fungi to fight COVID-19 infection via inhibition of SARS-CoV-2 lethal virus was perf...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325633/ https://www.ncbi.nlm.nih.gov/pubmed/35911157 http://dx.doi.org/10.1155/2022/5403757 |
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author | Sweilam, Sherouk Hussein Alqarni, Mohammed H. Youssef, Fadia S. |
author_facet | Sweilam, Sherouk Hussein Alqarni, Mohammed H. Youssef, Fadia S. |
author_sort | Sweilam, Sherouk Hussein |
collection | PubMed |
description | Therapeutic strategies based upon enzyme inhibition have recently gained higher attention in treating hazardous ailments. Herein, the potential use of seventy-two antimicrobial alkaloids isolated from marine-derived fungi to fight COVID-19 infection via inhibition of SARS-CoV-2 lethal virus was performed using in silico analyses. Molecular modelling was performed to assess their enzyme inhibitory potential on the main protease SARS-CoV-2 M(Pro), 3-chymotrypsin-like protease SARS-CoV-2 3CL(pro), and papain-like protease SARS-CoV-2 PL(pro) using Discovery Studio 4.5. Validation of the docking experiments was done by determination of RMSD (root mean square deviation) after redocking the superimposition of the cocrystalized ligands. Results showed that gymnastatin Z (72) showed the best fitting score in SARS-CoV-2 M(Pro) and SARS-CoV-2 3CL(pr) active sites with ∆G equal −34.15 and −34.28 Kcal/mol, respectively. Meanwhile, scalusamide C (62) displayed the highest fitting within SARS-CoV-2 PL(pro) active sites (∆G = −26.91 Kcal/mol) followed by eutypellazine M (57). ADMET/TOPKAT prediction displayed that eutypellazine M and scalusamide C showed better pharmacokinetic and pharmacodynamic properties. Gymnastatin Z is safer showing better toxicity criteria and higher rat oral LD(50) and rat chronic LOAEL (lowest observed adverse effect level). Chemometric analysis using principle component analysis (PCA) based on the binding energies observed for the compounds with respect to the three tested enzymes revealed the clustering of the compounds into different clusters. Eutypellazine M, scalusamide C, and gymnastatin Z appear in one cluster due to their closeness in activity. Thus, these compounds could serve as promising SARS-CoV-2 enzymes inhibitors that could help in alleviation of COVID-19 infection. Further investigations are recommended to confirm the results of molecular modelling. |
format | Online Article Text |
id | pubmed-9325633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-93256332022-07-28 Antimicrobial Alkaloids from Marine-Derived Fungi as Drug Leads versus COVID-19 Infection: A Computational Approach to Explore their Anti-COVID-19 Activity and ADMET Properties Sweilam, Sherouk Hussein Alqarni, Mohammed H. Youssef, Fadia S. Evid Based Complement Alternat Med Research Article Therapeutic strategies based upon enzyme inhibition have recently gained higher attention in treating hazardous ailments. Herein, the potential use of seventy-two antimicrobial alkaloids isolated from marine-derived fungi to fight COVID-19 infection via inhibition of SARS-CoV-2 lethal virus was performed using in silico analyses. Molecular modelling was performed to assess their enzyme inhibitory potential on the main protease SARS-CoV-2 M(Pro), 3-chymotrypsin-like protease SARS-CoV-2 3CL(pro), and papain-like protease SARS-CoV-2 PL(pro) using Discovery Studio 4.5. Validation of the docking experiments was done by determination of RMSD (root mean square deviation) after redocking the superimposition of the cocrystalized ligands. Results showed that gymnastatin Z (72) showed the best fitting score in SARS-CoV-2 M(Pro) and SARS-CoV-2 3CL(pr) active sites with ∆G equal −34.15 and −34.28 Kcal/mol, respectively. Meanwhile, scalusamide C (62) displayed the highest fitting within SARS-CoV-2 PL(pro) active sites (∆G = −26.91 Kcal/mol) followed by eutypellazine M (57). ADMET/TOPKAT prediction displayed that eutypellazine M and scalusamide C showed better pharmacokinetic and pharmacodynamic properties. Gymnastatin Z is safer showing better toxicity criteria and higher rat oral LD(50) and rat chronic LOAEL (lowest observed adverse effect level). Chemometric analysis using principle component analysis (PCA) based on the binding energies observed for the compounds with respect to the three tested enzymes revealed the clustering of the compounds into different clusters. Eutypellazine M, scalusamide C, and gymnastatin Z appear in one cluster due to their closeness in activity. Thus, these compounds could serve as promising SARS-CoV-2 enzymes inhibitors that could help in alleviation of COVID-19 infection. Further investigations are recommended to confirm the results of molecular modelling. Hindawi 2022-07-08 /pmc/articles/PMC9325633/ /pubmed/35911157 http://dx.doi.org/10.1155/2022/5403757 Text en Copyright © 2022 Sherouk Hussein Sweilam et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Sweilam, Sherouk Hussein Alqarni, Mohammed H. Youssef, Fadia S. Antimicrobial Alkaloids from Marine-Derived Fungi as Drug Leads versus COVID-19 Infection: A Computational Approach to Explore their Anti-COVID-19 Activity and ADMET Properties |
title | Antimicrobial Alkaloids from Marine-Derived Fungi as Drug Leads versus COVID-19 Infection: A Computational Approach to Explore their Anti-COVID-19 Activity and ADMET Properties |
title_full | Antimicrobial Alkaloids from Marine-Derived Fungi as Drug Leads versus COVID-19 Infection: A Computational Approach to Explore their Anti-COVID-19 Activity and ADMET Properties |
title_fullStr | Antimicrobial Alkaloids from Marine-Derived Fungi as Drug Leads versus COVID-19 Infection: A Computational Approach to Explore their Anti-COVID-19 Activity and ADMET Properties |
title_full_unstemmed | Antimicrobial Alkaloids from Marine-Derived Fungi as Drug Leads versus COVID-19 Infection: A Computational Approach to Explore their Anti-COVID-19 Activity and ADMET Properties |
title_short | Antimicrobial Alkaloids from Marine-Derived Fungi as Drug Leads versus COVID-19 Infection: A Computational Approach to Explore their Anti-COVID-19 Activity and ADMET Properties |
title_sort | antimicrobial alkaloids from marine-derived fungi as drug leads versus covid-19 infection: a computational approach to explore their anti-covid-19 activity and admet properties |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325633/ https://www.ncbi.nlm.nih.gov/pubmed/35911157 http://dx.doi.org/10.1155/2022/5403757 |
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