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Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding

BACKGROUND: The outbreak of coronavirus (SARS-CoV-2) disease caused more than 100,000,000 people get infected and over 2,200,000 people being killed worldwide. However, the current developed vaccines or drugs may be not effective in preventing the pandemic of COVID-19 due to the mutations of coronav...

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Autores principales: Yang, Li Jun, Chen, Rui Hong, Hamdoun, Sami, Coghi, Paolo, Ng, Jerome P.L., Zhang, David Wei, Guo, Xiaoling, Xia, Chenglai, Law, Betty Yuen Kwan, Wong, Vincent Kam Wai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier GmbH. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098048/
https://www.ncbi.nlm.nih.gov/pubmed/34029937
http://dx.doi.org/10.1016/j.phymed.2021.153591
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author Yang, Li Jun
Chen, Rui Hong
Hamdoun, Sami
Coghi, Paolo
Ng, Jerome P.L.
Zhang, David Wei
Guo, Xiaoling
Xia, Chenglai
Law, Betty Yuen Kwan
Wong, Vincent Kam Wai
author_facet Yang, Li Jun
Chen, Rui Hong
Hamdoun, Sami
Coghi, Paolo
Ng, Jerome P.L.
Zhang, David Wei
Guo, Xiaoling
Xia, Chenglai
Law, Betty Yuen Kwan
Wong, Vincent Kam Wai
author_sort Yang, Li Jun
collection PubMed
description BACKGROUND: The outbreak of coronavirus (SARS-CoV-2) disease caused more than 100,000,000 people get infected and over 2,200,000 people being killed worldwide. However, the current developed vaccines or drugs may be not effective in preventing the pandemic of COVID-19 due to the mutations of coronavirus and the severe side effects of the newly developed vaccines. Chinese herbal medicines and their active components play important antiviral activities. Corilagin exhibited antiviral effect on human immunodeficiency virus (HIV), hepatitis C virus (HCV) and Epstein-Barr virus (EBV). However, whether it blocks the interaction between SARS-CoV-2 RBD and hACE2 has not been elucidated. PURPOSE: To characterize an active compound, corilagin derived from Phyllanthus urinaria as potential SARS-CoV-2 entry inhibitors for its possible preventive application in daily anti-virus hygienic products. METHODS: Computational docking coupled with bio-layer interferometry, BLI were adopted to screen more than 1800 natural compounds for the identification of SARS-CoV-2 spike-RBD inhibitors. Corilagin was confirmed to have a strong binding affinity with SARS-CoV-2-RBD or human ACE2 (hACE2) protein by the BLI, ELISA and immunocytochemistry (ICC) assay. Furthermore, the inhibitory effect of viral infection of corilagin was assessed by in vitro pseudovirus system. Finally, the toxicity of corilagin was examined by using MTT assay and maximal tolerated dose (MTD) studies in C57BL/6 mice. RESULTS: Corilagin preferentially binds to a pocket that contains residues Cys 336 to Phe 374 of spike-RBD with a relatively low binding energy of -9.4 kcal/mol. BLI assay further confirmed that corilagin exhibits a relatively strong binding affinity to SARS-CoV-2-RBD and hACE2 protein. In addition, corilagin dose-dependently blocks SARS-CoV-2-RBD binding and abolishes the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of SARS-CoV-2 virus in human host cells. Finally, in vivo studies revealed that up to 300 mg/kg/day of corilagin was safe in C57BL/6 mice. Our findings suggest that corilagin could be a safe and potential antiviral agent against the COVID-19 acting through the blockade of the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors. CONCLUSION: Corilagin could be considered as a safe and environmental friendly anti-SARS-CoV-2 agent for its potential preventive application in daily anti-virus hygienic products.
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spelling pubmed-80980482021-05-05 Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding Yang, Li Jun Chen, Rui Hong Hamdoun, Sami Coghi, Paolo Ng, Jerome P.L. Zhang, David Wei Guo, Xiaoling Xia, Chenglai Law, Betty Yuen Kwan Wong, Vincent Kam Wai Phytomedicine Original Article BACKGROUND: The outbreak of coronavirus (SARS-CoV-2) disease caused more than 100,000,000 people get infected and over 2,200,000 people being killed worldwide. However, the current developed vaccines or drugs may be not effective in preventing the pandemic of COVID-19 due to the mutations of coronavirus and the severe side effects of the newly developed vaccines. Chinese herbal medicines and their active components play important antiviral activities. Corilagin exhibited antiviral effect on human immunodeficiency virus (HIV), hepatitis C virus (HCV) and Epstein-Barr virus (EBV). However, whether it blocks the interaction between SARS-CoV-2 RBD and hACE2 has not been elucidated. PURPOSE: To characterize an active compound, corilagin derived from Phyllanthus urinaria as potential SARS-CoV-2 entry inhibitors for its possible preventive application in daily anti-virus hygienic products. METHODS: Computational docking coupled with bio-layer interferometry, BLI were adopted to screen more than 1800 natural compounds for the identification of SARS-CoV-2 spike-RBD inhibitors. Corilagin was confirmed to have a strong binding affinity with SARS-CoV-2-RBD or human ACE2 (hACE2) protein by the BLI, ELISA and immunocytochemistry (ICC) assay. Furthermore, the inhibitory effect of viral infection of corilagin was assessed by in vitro pseudovirus system. Finally, the toxicity of corilagin was examined by using MTT assay and maximal tolerated dose (MTD) studies in C57BL/6 mice. RESULTS: Corilagin preferentially binds to a pocket that contains residues Cys 336 to Phe 374 of spike-RBD with a relatively low binding energy of -9.4 kcal/mol. BLI assay further confirmed that corilagin exhibits a relatively strong binding affinity to SARS-CoV-2-RBD and hACE2 protein. In addition, corilagin dose-dependently blocks SARS-CoV-2-RBD binding and abolishes the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of SARS-CoV-2 virus in human host cells. Finally, in vivo studies revealed that up to 300 mg/kg/day of corilagin was safe in C57BL/6 mice. Our findings suggest that corilagin could be a safe and potential antiviral agent against the COVID-19 acting through the blockade of the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors. CONCLUSION: Corilagin could be considered as a safe and environmental friendly anti-SARS-CoV-2 agent for its potential preventive application in daily anti-virus hygienic products. The Author(s). Published by Elsevier GmbH. 2021-07 2021-05-05 /pmc/articles/PMC8098048/ /pubmed/34029937 http://dx.doi.org/10.1016/j.phymed.2021.153591 Text en © 2021 The Author(s) 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 Original Article
Yang, Li Jun
Chen, Rui Hong
Hamdoun, Sami
Coghi, Paolo
Ng, Jerome P.L.
Zhang, David Wei
Guo, Xiaoling
Xia, Chenglai
Law, Betty Yuen Kwan
Wong, Vincent Kam Wai
Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding
title Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding
title_full Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding
title_fullStr Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding
title_full_unstemmed Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding
title_short Corilagin prevents SARS-CoV-2 infection by targeting RBD-ACE2 binding
title_sort corilagin prevents sars-cov-2 infection by targeting rbd-ace2 binding
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098048/
https://www.ncbi.nlm.nih.gov/pubmed/34029937
http://dx.doi.org/10.1016/j.phymed.2021.153591
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