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Small molecules in the treatment of COVID-19

The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small mo...

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Autores principales: Lei, Sibei, Chen, Xiaohua, Wu, Jieping, Duan, Xingmei, Men, Ke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719906/
https://www.ncbi.nlm.nih.gov/pubmed/36464706
http://dx.doi.org/10.1038/s41392-022-01249-8
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author Lei, Sibei
Chen, Xiaohua
Wu, Jieping
Duan, Xingmei
Men, Ke
author_facet Lei, Sibei
Chen, Xiaohua
Wu, Jieping
Duan, Xingmei
Men, Ke
author_sort Lei, Sibei
collection PubMed
description The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and M(pro), interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed.
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spelling pubmed-97199062022-12-06 Small molecules in the treatment of COVID-19 Lei, Sibei Chen, Xiaohua Wu, Jieping Duan, Xingmei Men, Ke Signal Transduct Target Ther Review Article The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and M(pro), interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed. Nature Publishing Group UK 2022-12-05 /pmc/articles/PMC9719906/ /pubmed/36464706 http://dx.doi.org/10.1038/s41392-022-01249-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review Article
Lei, Sibei
Chen, Xiaohua
Wu, Jieping
Duan, Xingmei
Men, Ke
Small molecules in the treatment of COVID-19
title Small molecules in the treatment of COVID-19
title_full Small molecules in the treatment of COVID-19
title_fullStr Small molecules in the treatment of COVID-19
title_full_unstemmed Small molecules in the treatment of COVID-19
title_short Small molecules in the treatment of COVID-19
title_sort small molecules in the treatment of covid-19
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719906/
https://www.ncbi.nlm.nih.gov/pubmed/36464706
http://dx.doi.org/10.1038/s41392-022-01249-8
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