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The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?

The interaction between the membrane spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the transmembrane angiotensin-converting enzyme 2 (ACE2) receptor of the human epithelial host cell is the first step of infection, which has a critical role for viral pathogene...

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Autores principales: Vianello, Annamaria, Del Turco, Serena, Babboni, Serena, Silvestrini, Beatrice, Ragusa, Rosetta, Caselli, Chiara, Melani, Luca, Fanucci, Luca, Basta, Giuseppina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301470/
https://www.ncbi.nlm.nih.gov/pubmed/34201505
http://dx.doi.org/10.3390/biomedicines9070710
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author Vianello, Annamaria
Del Turco, Serena
Babboni, Serena
Silvestrini, Beatrice
Ragusa, Rosetta
Caselli, Chiara
Melani, Luca
Fanucci, Luca
Basta, Giuseppina
author_facet Vianello, Annamaria
Del Turco, Serena
Babboni, Serena
Silvestrini, Beatrice
Ragusa, Rosetta
Caselli, Chiara
Melani, Luca
Fanucci, Luca
Basta, Giuseppina
author_sort Vianello, Annamaria
collection PubMed
description The interaction between the membrane spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the transmembrane angiotensin-converting enzyme 2 (ACE2) receptor of the human epithelial host cell is the first step of infection, which has a critical role for viral pathogenesis of the current coronavirus disease-2019 (COVID-19) pandemic. Following the binding between S1 subunit and ACE2 receptor, different serine proteases, including TMPRSS2 and furin, trigger and participate in the fusion of the viral envelope with the host cell membrane. On the basis of the high virulence and pathogenicity of SARS-CoV-2, other receptors have been found involved for viral binding and invasiveness of host cells. This review comprehensively discusses the mechanisms underlying the binding of SARS-CoV2 to ACE2 and putative alternative receptors, and the role of potential co-receptors and proteases in the early stages of SARS-CoV-2 infection. Given the short therapeutic time window within which to act to avoid the devastating evolution of the disease, we focused on potential therapeutic treatments—selected mainly among repurposing drugs—able to counteract the invasive front of proteases and mild inflammatory conditions, in order to prevent severe infection. Using existing approved drugs has the advantage of rapidly proceeding to clinical trials, low cost and, consequently, immediate and worldwide availability.
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spelling pubmed-83014702021-07-24 The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity? Vianello, Annamaria Del Turco, Serena Babboni, Serena Silvestrini, Beatrice Ragusa, Rosetta Caselli, Chiara Melani, Luca Fanucci, Luca Basta, Giuseppina Biomedicines Review The interaction between the membrane spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the transmembrane angiotensin-converting enzyme 2 (ACE2) receptor of the human epithelial host cell is the first step of infection, which has a critical role for viral pathogenesis of the current coronavirus disease-2019 (COVID-19) pandemic. Following the binding between S1 subunit and ACE2 receptor, different serine proteases, including TMPRSS2 and furin, trigger and participate in the fusion of the viral envelope with the host cell membrane. On the basis of the high virulence and pathogenicity of SARS-CoV-2, other receptors have been found involved for viral binding and invasiveness of host cells. This review comprehensively discusses the mechanisms underlying the binding of SARS-CoV2 to ACE2 and putative alternative receptors, and the role of potential co-receptors and proteases in the early stages of SARS-CoV-2 infection. Given the short therapeutic time window within which to act to avoid the devastating evolution of the disease, we focused on potential therapeutic treatments—selected mainly among repurposing drugs—able to counteract the invasive front of proteases and mild inflammatory conditions, in order to prevent severe infection. Using existing approved drugs has the advantage of rapidly proceeding to clinical trials, low cost and, consequently, immediate and worldwide availability. MDPI 2021-06-23 /pmc/articles/PMC8301470/ /pubmed/34201505 http://dx.doi.org/10.3390/biomedicines9070710 Text en © 2021 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 Review
Vianello, Annamaria
Del Turco, Serena
Babboni, Serena
Silvestrini, Beatrice
Ragusa, Rosetta
Caselli, Chiara
Melani, Luca
Fanucci, Luca
Basta, Giuseppina
The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?
title The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?
title_full The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?
title_fullStr The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?
title_full_unstemmed The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?
title_short The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?
title_sort fight against covid-19 on the multi-protease front and surroundings: could an early therapeutic approach with repositioning drugs prevent the disease severity?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301470/
https://www.ncbi.nlm.nih.gov/pubmed/34201505
http://dx.doi.org/10.3390/biomedicines9070710
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