Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective

Abstract Understanding the effects of metabolism on the rational design of novel and more effective drugs is still a considerable challenge. To the best of our knowledge, there are no entirely computational strategies that make it possible to predict these effects. From this perspective, the develop...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	João Paulo Almirão de Jesus, Letícia Cristina Assis, Alexandre Alves de Castro, Elaine Fontes Ferreira da Cunha, Eugenie Nepovimova, Kamil Kuca, Teodorico de Castro Ramalho, Felipe de Almeida La Porta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d3ed4d988abc460bbb0f802b9e741d1d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d3ed4d988abc460bbb0f802b9e741d1d
record_format	dspace
spelling	oai:doaj.org-article:d3ed4d988abc460bbb0f802b9e741d1d2021-12-02T18:01:48ZEffect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective10.1038/s41598-021-99451-12045-2322https://doaj.org/article/d3ed4d988abc460bbb0f802b9e741d1d2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99451-1https://doaj.org/toc/2045-2322Abstract Understanding the effects of metabolism on the rational design of novel and more effective drugs is still a considerable challenge. To the best of our knowledge, there are no entirely computational strategies that make it possible to predict these effects. From this perspective, the development of such methodologies could contribute to significantly reduce the side effects of medicines, leading to the emergence of more effective and safer drugs. Thereby, in this study, our strategy is based on simulating the electron ionization mass spectrometry (EI-MS) fragmentation of the drug molecules and combined with molecular docking and ADMET models in two different situations. In the first model, the drug is docked without considering the possible metabolic effects. In the second model, each of the intermediates from the EI-MS results is docked, and metabolism occurs before the drug accesses the biological target. As a proof of concept, in this work, we investigate the main antiviral drugs used in clinical research to treat COVID-19. As a result, our strategy made it possible to assess the biological activity and toxicity of all potential by-products. We believed that our findings provide new chemical insights that can benefit the rational development of novel drugs in the future.João Paulo Almirão de JesusLetícia Cristina AssisAlexandre Alves de CastroElaine Fontes Ferreira da CunhaEugenie NepovimovaKamil KucaTeodorico de Castro RamalhoFelipe de Almeida La PortaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q João Paulo Almirão de Jesus Letícia Cristina Assis Alexandre Alves de Castro Elaine Fontes Ferreira da Cunha Eugenie Nepovimova Kamil Kuca Teodorico de Castro Ramalho Felipe de Almeida La Porta Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective
description	Abstract Understanding the effects of metabolism on the rational design of novel and more effective drugs is still a considerable challenge. To the best of our knowledge, there are no entirely computational strategies that make it possible to predict these effects. From this perspective, the development of such methodologies could contribute to significantly reduce the side effects of medicines, leading to the emergence of more effective and safer drugs. Thereby, in this study, our strategy is based on simulating the electron ionization mass spectrometry (EI-MS) fragmentation of the drug molecules and combined with molecular docking and ADMET models in two different situations. In the first model, the drug is docked without considering the possible metabolic effects. In the second model, each of the intermediates from the EI-MS results is docked, and metabolism occurs before the drug accesses the biological target. As a proof of concept, in this work, we investigate the main antiviral drugs used in clinical research to treat COVID-19. As a result, our strategy made it possible to assess the biological activity and toxicity of all potential by-products. We believed that our findings provide new chemical insights that can benefit the rational development of novel drugs in the future.
format	article
author	João Paulo Almirão de Jesus Letícia Cristina Assis Alexandre Alves de Castro Elaine Fontes Ferreira da Cunha Eugenie Nepovimova Kamil Kuca Teodorico de Castro Ramalho Felipe de Almeida La Porta
author_facet	João Paulo Almirão de Jesus Letícia Cristina Assis Alexandre Alves de Castro Elaine Fontes Ferreira da Cunha Eugenie Nepovimova Kamil Kuca Teodorico de Castro Ramalho Felipe de Almeida La Porta
author_sort	João Paulo Almirão de Jesus
title	Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective
title_short	Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective
title_full	Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective
title_fullStr	Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective
title_full_unstemmed	Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective
title_sort	effect of drug metabolism in the treatment of sars-cov-2 from an entirely computational perspective
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d3ed4d988abc460bbb0f802b9e741d1d
work_keys_str_mv	AT joaopauloalmiraodejesus effectofdrugmetabolisminthetreatmentofsarscov2fromanentirelycomputationalperspective AT leticiacristinaassis effectofdrugmetabolisminthetreatmentofsarscov2fromanentirelycomputationalperspective AT alexandrealvesdecastro effectofdrugmetabolisminthetreatmentofsarscov2fromanentirelycomputationalperspective AT elainefontesferreiradacunha effectofdrugmetabolisminthetreatmentofsarscov2fromanentirelycomputationalperspective AT eugenienepovimova effectofdrugmetabolisminthetreatmentofsarscov2fromanentirelycomputationalperspective AT kamilkuca effectofdrugmetabolisminthetreatmentofsarscov2fromanentirelycomputationalperspective AT teodoricodecastroramalho effectofdrugmetabolisminthetreatmentofsarscov2fromanentirelycomputationalperspective AT felipedealmeidalaporta effectofdrugmetabolisminthetreatmentofsarscov2fromanentirelycomputationalperspective
_version_	1718378956920455168

Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective

Ejemplares similares