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Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2

Angiotensin-converting enzyme 2 (ACE2), a functional receptor for SARS-CoV, now appears likely to mediate 2019-nCoV entry into human cells. However, inhibitors such as PAP-1 and bergamottin have been discovered; both of them can preferentially bind to ACE2, prevent RBD Spike S protein from binding t...

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Autores principales: Li, Mengjia, Zhang, Yongzheng, Zeb, Amir, Wu, Yang, Cheng, Lufeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604380/
https://www.ncbi.nlm.nih.gov/pubmed/36293419
http://dx.doi.org/10.3390/ijms232012565
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author Li, Mengjia
Zhang, Yongzheng
Zeb, Amir
Wu, Yang
Cheng, Lufeng
author_facet Li, Mengjia
Zhang, Yongzheng
Zeb, Amir
Wu, Yang
Cheng, Lufeng
author_sort Li, Mengjia
collection PubMed
description Angiotensin-converting enzyme 2 (ACE2), a functional receptor for SARS-CoV, now appears likely to mediate 2019-nCoV entry into human cells. However, inhibitors such as PAP-1 and bergamottin have been discovered; both of them can preferentially bind to ACE2, prevent RBD Spike S protein from binding to ACE2, and reduce the binding sites for RBD Spike S protein. In addition, we investigated the binding energy of PAP-1 and bergamottin with ACE2 through molecular docking with bio-layer interferometry (BLI) and found relatively high binding affinity (KD = 48.5 nM, 53.1 nM) between the PAP-1 and bergamottin groups. In addition, the nanomolar fraction had no effect on growth of the AT-II cell, but 150 µM PAP-1 and 75 µM bergamottin inhibited the proliferation of AT-II cells in vitro by 75% and 68%, respectively. Meanwhile, they significantly reduced ACE2 mRNA and proteins by 67%, 58% and 55%, 41%, respectively. These results indicate that psoralen compounds PAP-1 and bergamottin binding to ACE2 protein could be further developed in the fight against COVID-19 infection during the current pandemic. However, attention should be paid to the damage to human alveolar type II epithelial cells.
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spelling pubmed-96043802022-10-27 Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2 Li, Mengjia Zhang, Yongzheng Zeb, Amir Wu, Yang Cheng, Lufeng Int J Mol Sci Article Angiotensin-converting enzyme 2 (ACE2), a functional receptor for SARS-CoV, now appears likely to mediate 2019-nCoV entry into human cells. However, inhibitors such as PAP-1 and bergamottin have been discovered; both of them can preferentially bind to ACE2, prevent RBD Spike S protein from binding to ACE2, and reduce the binding sites for RBD Spike S protein. In addition, we investigated the binding energy of PAP-1 and bergamottin with ACE2 through molecular docking with bio-layer interferometry (BLI) and found relatively high binding affinity (KD = 48.5 nM, 53.1 nM) between the PAP-1 and bergamottin groups. In addition, the nanomolar fraction had no effect on growth of the AT-II cell, but 150 µM PAP-1 and 75 µM bergamottin inhibited the proliferation of AT-II cells in vitro by 75% and 68%, respectively. Meanwhile, they significantly reduced ACE2 mRNA and proteins by 67%, 58% and 55%, 41%, respectively. These results indicate that psoralen compounds PAP-1 and bergamottin binding to ACE2 protein could be further developed in the fight against COVID-19 infection during the current pandemic. However, attention should be paid to the damage to human alveolar type II epithelial cells. MDPI 2022-10-19 /pmc/articles/PMC9604380/ /pubmed/36293419 http://dx.doi.org/10.3390/ijms232012565 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
Li, Mengjia
Zhang, Yongzheng
Zeb, Amir
Wu, Yang
Cheng, Lufeng
Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2
title Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2
title_full Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2
title_fullStr Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2
title_full_unstemmed Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2
title_short Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2
title_sort bergamottin and pap-1 induced ace2 degradation to alleviate infection of sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604380/
https://www.ncbi.nlm.nih.gov/pubmed/36293419
http://dx.doi.org/10.3390/ijms232012565
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