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Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus
The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2′-O-methyltransferase (nsp16) enzyme that is cruci...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100384/ https://www.ncbi.nlm.nih.gov/pubmed/35566072 http://dx.doi.org/10.3390/molecules27092721 |
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author | Sulimov, Alexey Kutov, Danil Ilin, Ivan Xiao, Yibei Jiang, Sheng Sulimov, Vladimir |
author_facet | Sulimov, Alexey Kutov, Danil Ilin, Ivan Xiao, Yibei Jiang, Sheng Sulimov, Vladimir |
author_sort | Sulimov, Alexey |
collection | PubMed |
description | The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2′-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM binds can disrupt the synthesis of viral proteins and, as a result, the replication of the virus. Here, we performed high-throughput docking into the SAM-binding site of nsp16 for almost 40 thousand structures, prepared for compounds from three libraries: Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library. For the top scoring ligands, semi-empirical quantum-chemical calculations were performed, to better estimate protein–ligand binding enthalpy. Relying upon the calculated binding energies and predicted docking poses, we selected 21 compounds for experimental testing. |
format | Online Article Text |
id | pubmed-9100384 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91003842022-05-14 Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus Sulimov, Alexey Kutov, Danil Ilin, Ivan Xiao, Yibei Jiang, Sheng Sulimov, Vladimir Molecules Article The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2′-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM binds can disrupt the synthesis of viral proteins and, as a result, the replication of the virus. Here, we performed high-throughput docking into the SAM-binding site of nsp16 for almost 40 thousand structures, prepared for compounds from three libraries: Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library. For the top scoring ligands, semi-empirical quantum-chemical calculations were performed, to better estimate protein–ligand binding enthalpy. Relying upon the calculated binding energies and predicted docking poses, we selected 21 compounds for experimental testing. MDPI 2022-04-23 /pmc/articles/PMC9100384/ /pubmed/35566072 http://dx.doi.org/10.3390/molecules27092721 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sulimov, Alexey Kutov, Danil Ilin, Ivan Xiao, Yibei Jiang, Sheng Sulimov, Vladimir Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus |
title | Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus |
title_full | Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus |
title_fullStr | Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus |
title_full_unstemmed | Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus |
title_short | Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus |
title_sort | novel inhibitors of 2′-o-methyltransferase of the sars-cov-2 coronavirus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100384/ https://www.ncbi.nlm.nih.gov/pubmed/35566072 http://dx.doi.org/10.3390/molecules27092721 |
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