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Computational and experimental studies of salvianolic acid A targets 3C protease to inhibit enterovirus 71 infection
Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by enterovirus (EV) infection. EV71 is one of the major pathogens causing hand, foot, and mouth disease and is more likely to cause exacerbation and death than other enteroviruses. Although a monovalent vaccine for...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017496/ https://www.ncbi.nlm.nih.gov/pubmed/36937869 http://dx.doi.org/10.3389/fphar.2023.1118584 |
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author | Shi, Sai Xie, Lei Ma, Sen Xu, Binghong An, Hailong Ye, Sheng Wang, Yaxin |
author_facet | Shi, Sai Xie, Lei Ma, Sen Xu, Binghong An, Hailong Ye, Sheng Wang, Yaxin |
author_sort | Shi, Sai |
collection | PubMed |
description | Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by enterovirus (EV) infection. EV71 is one of the major pathogens causing hand, foot, and mouth disease and is more likely to cause exacerbation and death than other enteroviruses. Although a monovalent vaccine for EV71 has been developed, there are no clinically available anti-EV71 specific drugs. Here, we performed virtual screening and biological experiments based on the traditional Chinese medicine monomer library. We identified a traditional Chinese medicine monomer, Salvianolic acid A (SA), a polyphenolic compound isolated from Salvia miltiorrhiza. Salvianolic acid A inhibits EV71 virus infection in a concentration-dependent manner, and its antiviral activity is higher than that of other reported natural polyphenols and has a high biosafety. Furthermore, molecular dynamics simulations showed that salvianolic acid A can anchor to E71, a member of the enzyme catalytic triad, and cause H40 to move away from the catalytic center. Meanwhile, molecular mechanics generalized born surface area (MMGBSA) and steered molecular dynamics (SMD) results showed that the P1 group of SA was most easily unbound to the S1 pocket of 3C(pro), which provided theoretical support to further improve the affinity of salvianolic acid A with 3C(pro). These findings suggest that salvianolic acid A is a novel EV71 3C(pro) inhibitor with excellent antiviral activity and is a promising candidate for clinical studies. |
format | Online Article Text |
id | pubmed-10017496 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100174962023-03-17 Computational and experimental studies of salvianolic acid A targets 3C protease to inhibit enterovirus 71 infection Shi, Sai Xie, Lei Ma, Sen Xu, Binghong An, Hailong Ye, Sheng Wang, Yaxin Front Pharmacol Pharmacology Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by enterovirus (EV) infection. EV71 is one of the major pathogens causing hand, foot, and mouth disease and is more likely to cause exacerbation and death than other enteroviruses. Although a monovalent vaccine for EV71 has been developed, there are no clinically available anti-EV71 specific drugs. Here, we performed virtual screening and biological experiments based on the traditional Chinese medicine monomer library. We identified a traditional Chinese medicine monomer, Salvianolic acid A (SA), a polyphenolic compound isolated from Salvia miltiorrhiza. Salvianolic acid A inhibits EV71 virus infection in a concentration-dependent manner, and its antiviral activity is higher than that of other reported natural polyphenols and has a high biosafety. Furthermore, molecular dynamics simulations showed that salvianolic acid A can anchor to E71, a member of the enzyme catalytic triad, and cause H40 to move away from the catalytic center. Meanwhile, molecular mechanics generalized born surface area (MMGBSA) and steered molecular dynamics (SMD) results showed that the P1 group of SA was most easily unbound to the S1 pocket of 3C(pro), which provided theoretical support to further improve the affinity of salvianolic acid A with 3C(pro). These findings suggest that salvianolic acid A is a novel EV71 3C(pro) inhibitor with excellent antiviral activity and is a promising candidate for clinical studies. Frontiers Media S.A. 2023-03-02 /pmc/articles/PMC10017496/ /pubmed/36937869 http://dx.doi.org/10.3389/fphar.2023.1118584 Text en Copyright © 2023 Shi, Xie, Ma, Xu, An, Ye and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Shi, Sai Xie, Lei Ma, Sen Xu, Binghong An, Hailong Ye, Sheng Wang, Yaxin Computational and experimental studies of salvianolic acid A targets 3C protease to inhibit enterovirus 71 infection |
title | Computational and experimental studies of salvianolic acid A targets 3C protease to inhibit enterovirus 71 infection |
title_full | Computational and experimental studies of salvianolic acid A targets 3C protease to inhibit enterovirus 71 infection |
title_fullStr | Computational and experimental studies of salvianolic acid A targets 3C protease to inhibit enterovirus 71 infection |
title_full_unstemmed | Computational and experimental studies of salvianolic acid A targets 3C protease to inhibit enterovirus 71 infection |
title_short | Computational and experimental studies of salvianolic acid A targets 3C protease to inhibit enterovirus 71 infection |
title_sort | computational and experimental studies of salvianolic acid a targets 3c protease to inhibit enterovirus 71 infection |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017496/ https://www.ncbi.nlm.nih.gov/pubmed/36937869 http://dx.doi.org/10.3389/fphar.2023.1118584 |
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