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Identification of SARS-CoV-2 surface therapeutic targets and drugs using molecular modeling methods for inhibition of the virus entry

Although COVID-19 emerged as a major concern to public health around the world, no licensed medication has been found as of yet to efficiently stop the virus spread and treat the infection. The SARS-CoV-2 entry into the host cell is driven by the direct interaction of the S1 domain with the ACE-2 re...

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Autores principales: Farhadian, Sadegh, Heidari-Soureshjani, Ehsan, Hashemi-Shahraki, Fatemeh, Hasanpour-Dehkordi, Ali, Uversky, Vladimir N., Shirani, Majid, Shareghi, Behzad, Sadeghi, Mehraban, Pirali, Esmaeil, Hadi-Alijanvand, Saeid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797986/
https://www.ncbi.nlm.nih.gov/pubmed/35125515
http://dx.doi.org/10.1016/j.molstruc.2022.132488
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author Farhadian, Sadegh
Heidari-Soureshjani, Ehsan
Hashemi-Shahraki, Fatemeh
Hasanpour-Dehkordi, Ali
Uversky, Vladimir N.
Shirani, Majid
Shareghi, Behzad
Sadeghi, Mehraban
Pirali, Esmaeil
Hadi-Alijanvand, Saeid
author_facet Farhadian, Sadegh
Heidari-Soureshjani, Ehsan
Hashemi-Shahraki, Fatemeh
Hasanpour-Dehkordi, Ali
Uversky, Vladimir N.
Shirani, Majid
Shareghi, Behzad
Sadeghi, Mehraban
Pirali, Esmaeil
Hadi-Alijanvand, Saeid
author_sort Farhadian, Sadegh
collection PubMed
description Although COVID-19 emerged as a major concern to public health around the world, no licensed medication has been found as of yet to efficiently stop the virus spread and treat the infection. The SARS-CoV-2 entry into the host cell is driven by the direct interaction of the S1 domain with the ACE-2 receptor followed by conformational changes in the S2 domain, as a result of which fusion peptide is inserted into the target cell membrane, and the fusion process is mediated by the specific interactions between the heptad repeats 1 and 2 (HR1 and HR2) that form the six-helical bundle. Since blocking this interaction between HRs stops virus fusion and prevents its subsequent replication, the HRs inhibitors can be used as anti-COVID drugs. The initial drug selection is based on existing molecular databases to screen for molecules that may have a therapeutic effect on coronavirus. Based on these premises, we chose two approved drugs to investigate their interactions with the HRs (based on docking methods). To this end, molecular dynamics simulations and molecular docking were carried out to investigate the changes in the structure of the SARS-CoV-2 spike protein. Our results revealed, cefpiramide has the highest affinity to S protein, thereby revealing its potential to become an anti-COVID-19 clinical medicine. Therefore, this study offers new ways to re-use existing drugs to combat SARS-CoV-2 infection.
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spelling pubmed-87979862022-01-31 Identification of SARS-CoV-2 surface therapeutic targets and drugs using molecular modeling methods for inhibition of the virus entry Farhadian, Sadegh Heidari-Soureshjani, Ehsan Hashemi-Shahraki, Fatemeh Hasanpour-Dehkordi, Ali Uversky, Vladimir N. Shirani, Majid Shareghi, Behzad Sadeghi, Mehraban Pirali, Esmaeil Hadi-Alijanvand, Saeid J Mol Struct Article Although COVID-19 emerged as a major concern to public health around the world, no licensed medication has been found as of yet to efficiently stop the virus spread and treat the infection. The SARS-CoV-2 entry into the host cell is driven by the direct interaction of the S1 domain with the ACE-2 receptor followed by conformational changes in the S2 domain, as a result of which fusion peptide is inserted into the target cell membrane, and the fusion process is mediated by the specific interactions between the heptad repeats 1 and 2 (HR1 and HR2) that form the six-helical bundle. Since blocking this interaction between HRs stops virus fusion and prevents its subsequent replication, the HRs inhibitors can be used as anti-COVID drugs. The initial drug selection is based on existing molecular databases to screen for molecules that may have a therapeutic effect on coronavirus. Based on these premises, we chose two approved drugs to investigate their interactions with the HRs (based on docking methods). To this end, molecular dynamics simulations and molecular docking were carried out to investigate the changes in the structure of the SARS-CoV-2 spike protein. Our results revealed, cefpiramide has the highest affinity to S protein, thereby revealing its potential to become an anti-COVID-19 clinical medicine. Therefore, this study offers new ways to re-use existing drugs to combat SARS-CoV-2 infection. Elsevier B.V. 2022-05-15 2022-01-28 /pmc/articles/PMC8797986/ /pubmed/35125515 http://dx.doi.org/10.1016/j.molstruc.2022.132488 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
Farhadian, Sadegh
Heidari-Soureshjani, Ehsan
Hashemi-Shahraki, Fatemeh
Hasanpour-Dehkordi, Ali
Uversky, Vladimir N.
Shirani, Majid
Shareghi, Behzad
Sadeghi, Mehraban
Pirali, Esmaeil
Hadi-Alijanvand, Saeid
Identification of SARS-CoV-2 surface therapeutic targets and drugs using molecular modeling methods for inhibition of the virus entry
title Identification of SARS-CoV-2 surface therapeutic targets and drugs using molecular modeling methods for inhibition of the virus entry
title_full Identification of SARS-CoV-2 surface therapeutic targets and drugs using molecular modeling methods for inhibition of the virus entry
title_fullStr Identification of SARS-CoV-2 surface therapeutic targets and drugs using molecular modeling methods for inhibition of the virus entry
title_full_unstemmed Identification of SARS-CoV-2 surface therapeutic targets and drugs using molecular modeling methods for inhibition of the virus entry
title_short Identification of SARS-CoV-2 surface therapeutic targets and drugs using molecular modeling methods for inhibition of the virus entry
title_sort identification of sars-cov-2 surface therapeutic targets and drugs using molecular modeling methods for inhibition of the virus entry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797986/
https://www.ncbi.nlm.nih.gov/pubmed/35125515
http://dx.doi.org/10.1016/j.molstruc.2022.132488
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