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Fluorine Atoms on C(6)H(5)-Corrole Affect the Interaction with M(pro) and PL(pro) Proteases of SARS-CoV-2: Molecular Docking and 2D-QSAR Approaches

The chymotrypsin-like cysteine protease (3CL(pro), also known as main protease—M(pro)) and papain-like protease (PL(pro)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been used as the main targets for screening potential synthetic inhibitors for posterior in vitro evaluation...

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Autores principales: Chaves, Otávio Augusto, Rodrigues-Santos, Cláudio Eduardo, Echevarria, Áurea, Sacramento, Carolina Q., Fintelman-Rodrigues, Natalia, Temerozo, Jairo R., Castro-Faria-Neto, Hugo Caire, Souza, Thiago Moreno Lopes e
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505658/
https://www.ncbi.nlm.nih.gov/pubmed/36142848
http://dx.doi.org/10.3390/ijms231810936
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author Chaves, Otávio Augusto
Rodrigues-Santos, Cláudio Eduardo
Echevarria, Áurea
Sacramento, Carolina Q.
Fintelman-Rodrigues, Natalia
Temerozo, Jairo R.
Castro-Faria-Neto, Hugo Caire
Souza, Thiago Moreno Lopes e
author_facet Chaves, Otávio Augusto
Rodrigues-Santos, Cláudio Eduardo
Echevarria, Áurea
Sacramento, Carolina Q.
Fintelman-Rodrigues, Natalia
Temerozo, Jairo R.
Castro-Faria-Neto, Hugo Caire
Souza, Thiago Moreno Lopes e
author_sort Chaves, Otávio Augusto
collection PubMed
description The chymotrypsin-like cysteine protease (3CL(pro), also known as main protease—M(pro)) and papain-like protease (PL(pro)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been used as the main targets for screening potential synthetic inhibitors for posterior in vitro evaluation of the most promising compounds. In this sense, the present work reports for the first time the evaluation of the interaction between M(pro)/PL(pro) with a series of 17 porphyrin analogues-corrole (C1), meso-aryl-corrole (C2), and 15 fluorinated-meso-aryl-corrole derivatives (C3–C17) via molecular docking calculations. The impact of fluorine atoms on meso-aryl-corrole structure was also evaluated in terms of binding affinity and physical-chemical properties by two-dimensional quantitative structure–activity relationship (2D-QSAR). The presence of phenyl moieties increased the binding capacity of corrole for both proteases and depending on the position of fluorine atoms might impact positively or negatively the binding capacity. For M(pro) the para-fluorine atoms might decrease drastically the binding capacity, while for PL(pro) there was a certain increase in the binding affinity of fluorinated-corroles with the increase of fluorine atoms into meso-aryl-corrole structure mainly from tri-fluorinated insertions. The 2D-QSAR models indicated two separated regions of higher and lower affinity for M(pro):C1–C17 based on dual electronic parameters (σ(I) and σ(R)), as well as one model was obtained with a correlation between the docking score value of M(pro):C2–C17 and the corresponding (13)C nuclear magnetic resonance (NMR) chemical shifts of the sp(2) carbon atoms (δ(C-1) and δ(C-2)) of C2–C17. Overall, the fluorinated-meso-aryl-corrole derivatives showed favorable in silico parameters as potential synthetic compounds for future in vitro assays on the inhibition of SARS-CoV-2 replication.
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spelling pubmed-95056582022-09-24 Fluorine Atoms on C(6)H(5)-Corrole Affect the Interaction with M(pro) and PL(pro) Proteases of SARS-CoV-2: Molecular Docking and 2D-QSAR Approaches Chaves, Otávio Augusto Rodrigues-Santos, Cláudio Eduardo Echevarria, Áurea Sacramento, Carolina Q. Fintelman-Rodrigues, Natalia Temerozo, Jairo R. Castro-Faria-Neto, Hugo Caire Souza, Thiago Moreno Lopes e Int J Mol Sci Article The chymotrypsin-like cysteine protease (3CL(pro), also known as main protease—M(pro)) and papain-like protease (PL(pro)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been used as the main targets for screening potential synthetic inhibitors for posterior in vitro evaluation of the most promising compounds. In this sense, the present work reports for the first time the evaluation of the interaction between M(pro)/PL(pro) with a series of 17 porphyrin analogues-corrole (C1), meso-aryl-corrole (C2), and 15 fluorinated-meso-aryl-corrole derivatives (C3–C17) via molecular docking calculations. The impact of fluorine atoms on meso-aryl-corrole structure was also evaluated in terms of binding affinity and physical-chemical properties by two-dimensional quantitative structure–activity relationship (2D-QSAR). The presence of phenyl moieties increased the binding capacity of corrole for both proteases and depending on the position of fluorine atoms might impact positively or negatively the binding capacity. For M(pro) the para-fluorine atoms might decrease drastically the binding capacity, while for PL(pro) there was a certain increase in the binding affinity of fluorinated-corroles with the increase of fluorine atoms into meso-aryl-corrole structure mainly from tri-fluorinated insertions. The 2D-QSAR models indicated two separated regions of higher and lower affinity for M(pro):C1–C17 based on dual electronic parameters (σ(I) and σ(R)), as well as one model was obtained with a correlation between the docking score value of M(pro):C2–C17 and the corresponding (13)C nuclear magnetic resonance (NMR) chemical shifts of the sp(2) carbon atoms (δ(C-1) and δ(C-2)) of C2–C17. Overall, the fluorinated-meso-aryl-corrole derivatives showed favorable in silico parameters as potential synthetic compounds for future in vitro assays on the inhibition of SARS-CoV-2 replication. MDPI 2022-09-19 /pmc/articles/PMC9505658/ /pubmed/36142848 http://dx.doi.org/10.3390/ijms231810936 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
Chaves, Otávio Augusto
Rodrigues-Santos, Cláudio Eduardo
Echevarria, Áurea
Sacramento, Carolina Q.
Fintelman-Rodrigues, Natalia
Temerozo, Jairo R.
Castro-Faria-Neto, Hugo Caire
Souza, Thiago Moreno Lopes e
Fluorine Atoms on C(6)H(5)-Corrole Affect the Interaction with M(pro) and PL(pro) Proteases of SARS-CoV-2: Molecular Docking and 2D-QSAR Approaches
title Fluorine Atoms on C(6)H(5)-Corrole Affect the Interaction with M(pro) and PL(pro) Proteases of SARS-CoV-2: Molecular Docking and 2D-QSAR Approaches
title_full Fluorine Atoms on C(6)H(5)-Corrole Affect the Interaction with M(pro) and PL(pro) Proteases of SARS-CoV-2: Molecular Docking and 2D-QSAR Approaches
title_fullStr Fluorine Atoms on C(6)H(5)-Corrole Affect the Interaction with M(pro) and PL(pro) Proteases of SARS-CoV-2: Molecular Docking and 2D-QSAR Approaches
title_full_unstemmed Fluorine Atoms on C(6)H(5)-Corrole Affect the Interaction with M(pro) and PL(pro) Proteases of SARS-CoV-2: Molecular Docking and 2D-QSAR Approaches
title_short Fluorine Atoms on C(6)H(5)-Corrole Affect the Interaction with M(pro) and PL(pro) Proteases of SARS-CoV-2: Molecular Docking and 2D-QSAR Approaches
title_sort fluorine atoms on c(6)h(5)-corrole affect the interaction with m(pro) and pl(pro) proteases of sars-cov-2: molecular docking and 2d-qsar approaches
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505658/
https://www.ncbi.nlm.nih.gov/pubmed/36142848
http://dx.doi.org/10.3390/ijms231810936
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