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Integrated computational approach towards identification of HSPG and ACE2 mimicking moieties for SARS-CoV-2 inhibition
A key step to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is to prevent the entry of the virus into the host cells. The receptor-binding domains (RBDs) of spike proteins of SARS-CoV and other human coronaviruses utilize heparan sulfate proteoglycans (HSPGs) as the...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier B.V.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578758/ https://www.ncbi.nlm.nih.gov/pubmed/36276265 http://dx.doi.org/10.1016/j.molliq.2022.120566 |
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author | Sreekumar, Sreya M. Kuthe, Abhaykumar Chandra Tripathi, Satyendra C. Patil, Ganesh Ravikumar, C. |
author_facet | Sreekumar, Sreya M. Kuthe, Abhaykumar Chandra Tripathi, Satyendra C. Patil, Ganesh Ravikumar, C. |
author_sort | Sreekumar, Sreya |
collection | PubMed |
description | A key step to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is to prevent the entry of the virus into the host cells. The receptor-binding domains (RBDs) of spike proteins of SARS-CoV and other human coronaviruses utilize heparan sulfate proteoglycans (HSPGs) as the primary receptors for their accumulation on the cell surface and then scan for binding to the main entry receptor angiotensin-converting enzyme 2 (ACE2). SARS-CoV and SARS-CoV-2 share structurally similar RBDs and therefore, it is possible that SARS-COV-2 primarily binds to HSPGs followed by binding to the ACE2 receptors. A promising strategy to inhibit virus infection is to circulate exogenous bioactive moieties structurally mimicking cellular HSPG and ACE2 which act as decoy receptors binding to SARS-CoV-2 and competitively inhibit virus entry to the host cells mediated by cellular-bound HSPG and ACE2. Using a molecular docking tool, we identified carboxymethyl benzyl amide sulfonate (CMBS) and polyanetholesulfonic acid (PAS) as the suitable HSPG mimicking ligands, and Paenibacillus sp. B38-derived carboxypeptidase (B38-CAP) and Bacillus subtilis-derived carboxypeptidase (BS-CAP) as the potential ACE2-like enzymes having a strong binding affinity to the spike proteins as that of cellular HSPG and ACE2. Further, the binding stability and compactness of these moieties with SARS-CoV-2 were analyzed through molecular dynamics (MD) simulations, and the results indicated that these moieties form well-stable complexes with the RBD of spike proteins. The identified moieties could be conjugated to the surfaces of non-toxic nanoparticles to provide multiple interactions to efficiently shield SARS-CoV-2, and inhibit viral entry to the host cells. |
format | Online Article Text |
id | pubmed-9578758 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95787582022-10-19 Integrated computational approach towards identification of HSPG and ACE2 mimicking moieties for SARS-CoV-2 inhibition Sreekumar, Sreya M. Kuthe, Abhaykumar Chandra Tripathi, Satyendra C. Patil, Ganesh Ravikumar, C. J Mol Liq Article A key step to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is to prevent the entry of the virus into the host cells. The receptor-binding domains (RBDs) of spike proteins of SARS-CoV and other human coronaviruses utilize heparan sulfate proteoglycans (HSPGs) as the primary receptors for their accumulation on the cell surface and then scan for binding to the main entry receptor angiotensin-converting enzyme 2 (ACE2). SARS-CoV and SARS-CoV-2 share structurally similar RBDs and therefore, it is possible that SARS-COV-2 primarily binds to HSPGs followed by binding to the ACE2 receptors. A promising strategy to inhibit virus infection is to circulate exogenous bioactive moieties structurally mimicking cellular HSPG and ACE2 which act as decoy receptors binding to SARS-CoV-2 and competitively inhibit virus entry to the host cells mediated by cellular-bound HSPG and ACE2. Using a molecular docking tool, we identified carboxymethyl benzyl amide sulfonate (CMBS) and polyanetholesulfonic acid (PAS) as the suitable HSPG mimicking ligands, and Paenibacillus sp. B38-derived carboxypeptidase (B38-CAP) and Bacillus subtilis-derived carboxypeptidase (BS-CAP) as the potential ACE2-like enzymes having a strong binding affinity to the spike proteins as that of cellular HSPG and ACE2. Further, the binding stability and compactness of these moieties with SARS-CoV-2 were analyzed through molecular dynamics (MD) simulations, and the results indicated that these moieties form well-stable complexes with the RBD of spike proteins. The identified moieties could be conjugated to the surfaces of non-toxic nanoparticles to provide multiple interactions to efficiently shield SARS-CoV-2, and inhibit viral entry to the host cells. Elsevier B.V. 2022-12-01 2022-10-13 /pmc/articles/PMC9578758/ /pubmed/36276265 http://dx.doi.org/10.1016/j.molliq.2022.120566 Text en © 2022 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Sreekumar, Sreya M. Kuthe, Abhaykumar Chandra Tripathi, Satyendra C. Patil, Ganesh Ravikumar, C. Integrated computational approach towards identification of HSPG and ACE2 mimicking moieties for SARS-CoV-2 inhibition |
title | Integrated computational approach towards identification of HSPG and ACE2 mimicking moieties for SARS-CoV-2 inhibition |
title_full | Integrated computational approach towards identification of HSPG and ACE2 mimicking moieties for SARS-CoV-2 inhibition |
title_fullStr | Integrated computational approach towards identification of HSPG and ACE2 mimicking moieties for SARS-CoV-2 inhibition |
title_full_unstemmed | Integrated computational approach towards identification of HSPG and ACE2 mimicking moieties for SARS-CoV-2 inhibition |
title_short | Integrated computational approach towards identification of HSPG and ACE2 mimicking moieties for SARS-CoV-2 inhibition |
title_sort | integrated computational approach towards identification of hspg and ace2 mimicking moieties for sars-cov-2 inhibition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578758/ https://www.ncbi.nlm.nih.gov/pubmed/36276265 http://dx.doi.org/10.1016/j.molliq.2022.120566 |
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