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Remdesivir analog as SARS-CoV-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement
By the end of 2019, a novel strain of the corona viral family named SARS-CoV-2 emerged in Wuhan, China and started to spread worldwide causing one of the most dangerous lethal pandemics. Researchers utilized various reported inhibitors and drug databases for virtual screening analysis against this n...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366421/ https://www.ncbi.nlm.nih.gov/pubmed/36105996 http://dx.doi.org/10.1039/d2ra00486k |
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author | Said, Mohamed A. Albohy, Amgad Abdelrahman, Mohamed A. Ibarhim, Hany S. |
author_facet | Said, Mohamed A. Albohy, Amgad Abdelrahman, Mohamed A. Ibarhim, Hany S. |
author_sort | Said, Mohamed A. |
collection | PubMed |
description | By the end of 2019, a novel strain of the corona viral family named SARS-CoV-2 emerged in Wuhan, China and started to spread worldwide causing one of the most dangerous lethal pandemics. Researchers utilized various reported inhibitors and drug databases for virtual screening analysis against this novel strain. Later on, they succeeded to fish and repurpose remdesivir, an antiviral nucleotide analogue that inhibits RNA polymerase of the Ebola virus, as a promising candidate against SARS-CoV-2. In this study, we used the interactions of the co-crystallized metabolite of remdesivir with SARS-CoV-2 RdRp isozyme (PDB 7BV2) to design an analog with potential extra activity. This design was based on a scaffold replacement of a pyrrolotriazine moiety. This design was guided by a generated structure-based pharmacophore. The database generated from scaffold replacement was subjected to molecular docking and molecular dynamics simulations within the active site of SARS-CoV-2 RdRp (PDB 7BV2) to suggest HA-130383 and HA-130384 as potential lead compounds. |
format | Online Article Text |
id | pubmed-9366421 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-93664212022-09-13 Remdesivir analog as SARS-CoV-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement Said, Mohamed A. Albohy, Amgad Abdelrahman, Mohamed A. Ibarhim, Hany S. RSC Adv Chemistry By the end of 2019, a novel strain of the corona viral family named SARS-CoV-2 emerged in Wuhan, China and started to spread worldwide causing one of the most dangerous lethal pandemics. Researchers utilized various reported inhibitors and drug databases for virtual screening analysis against this novel strain. Later on, they succeeded to fish and repurpose remdesivir, an antiviral nucleotide analogue that inhibits RNA polymerase of the Ebola virus, as a promising candidate against SARS-CoV-2. In this study, we used the interactions of the co-crystallized metabolite of remdesivir with SARS-CoV-2 RdRp isozyme (PDB 7BV2) to design an analog with potential extra activity. This design was based on a scaffold replacement of a pyrrolotriazine moiety. This design was guided by a generated structure-based pharmacophore. The database generated from scaffold replacement was subjected to molecular docking and molecular dynamics simulations within the active site of SARS-CoV-2 RdRp (PDB 7BV2) to suggest HA-130383 and HA-130384 as potential lead compounds. The Royal Society of Chemistry 2022-08-11 /pmc/articles/PMC9366421/ /pubmed/36105996 http://dx.doi.org/10.1039/d2ra00486k Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Said, Mohamed A. Albohy, Amgad Abdelrahman, Mohamed A. Ibarhim, Hany S. Remdesivir analog as SARS-CoV-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement |
title | Remdesivir analog as SARS-CoV-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement |
title_full | Remdesivir analog as SARS-CoV-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement |
title_fullStr | Remdesivir analog as SARS-CoV-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement |
title_full_unstemmed | Remdesivir analog as SARS-CoV-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement |
title_short | Remdesivir analog as SARS-CoV-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement |
title_sort | remdesivir analog as sars-cov-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366421/ https://www.ncbi.nlm.nih.gov/pubmed/36105996 http://dx.doi.org/10.1039/d2ra00486k |
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