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Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming
Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2′) cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, an...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287953/ https://www.ncbi.nlm.nih.gov/pubmed/32455942 http://dx.doi.org/10.3390/molecules25102424 |
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author | Barile, Elisa Baggio, Carlo Gambini, Luca Shiryaev, Sergey A. Strongin, Alex Y. Pellecchia, Maurizio |
author_facet | Barile, Elisa Baggio, Carlo Gambini, Luca Shiryaev, Sergey A. Strongin, Alex Y. Pellecchia, Maurizio |
author_sort | Barile, Elisa |
collection | PubMed |
description | Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2′) cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible mutations in the receptor binding domain and in the S1 and S2′ cleavage sites of their spike glycoprotein. However, there remains some confusion on the relative roles of the possible serine proteases involved for priming. Using anthrax toxin as a model system, we show that in vivo inhibition of priming by pan-active serine protease inhibitors can be effective at suppressing toxicity. Hence, our studies should encourage further efforts in developing either pan-serine protease inhibitors or inhibitor cocktails to target SARS-CoV2 and potentially ward off future pandemics that could develop because of additional mutations in the S-protein priming sequence in coronaviruses. |
format | Online Article Text |
id | pubmed-7287953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72879532020-06-15 Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming Barile, Elisa Baggio, Carlo Gambini, Luca Shiryaev, Sergey A. Strongin, Alex Y. Pellecchia, Maurizio Molecules Article Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2′) cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible mutations in the receptor binding domain and in the S1 and S2′ cleavage sites of their spike glycoprotein. However, there remains some confusion on the relative roles of the possible serine proteases involved for priming. Using anthrax toxin as a model system, we show that in vivo inhibition of priming by pan-active serine protease inhibitors can be effective at suppressing toxicity. Hence, our studies should encourage further efforts in developing either pan-serine protease inhibitors or inhibitor cocktails to target SARS-CoV2 and potentially ward off future pandemics that could develop because of additional mutations in the S-protein priming sequence in coronaviruses. MDPI 2020-05-22 /pmc/articles/PMC7287953/ /pubmed/32455942 http://dx.doi.org/10.3390/molecules25102424 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Barile, Elisa Baggio, Carlo Gambini, Luca Shiryaev, Sergey A. Strongin, Alex Y. Pellecchia, Maurizio Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming |
title | Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming |
title_full | Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming |
title_fullStr | Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming |
title_full_unstemmed | Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming |
title_short | Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming |
title_sort | potential therapeutic targeting of coronavirus spike glycoprotein priming |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287953/ https://www.ncbi.nlm.nih.gov/pubmed/32455942 http://dx.doi.org/10.3390/molecules25102424 |
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