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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F21%3A50018424" target="_blank" >RIV/62690094:18470/21:50018424 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41598-021-99451-1" target="_blank" >https://www.nature.com/articles/s41598-021-99451-1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-021-99451-1" target="_blank" >10.1038/s41598-021-99451-1</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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. © 2021, The Author(s).

Název v anglickém jazyce

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

Popis výsledku anglicky

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. © 2021, The Author(s).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Scientific reports

ISSN

2045-2322

e-ISSN

—

Svazek periodika

11

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

16

Strana od-do

"Article number: 19998"

Kód UT WoS článku

000706376200081

EID výsledku v databázi Scopus

2-s2.0-85116583690