In Silico Identification and Validation of Organic Triazole Based Ligands as Potential Inhibitory Drug Compounds of SARS-CoV-2 Main Protease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F21%3A00548982" target="_blank" >RIV/86652036:_____/21:00548982 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/21:10435145 RIV/60460709:41210/21:88336

Výsledek na webu

<a href="https://www.mdpi.com/1420-3049/26/20/6199" target="_blank" >https://www.mdpi.com/1420-3049/26/20/6199</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules26206199" target="_blank" >10.3390/molecules26206199</a>

Jazyk výsledku

angličtina

Název v původním jazyce

In Silico Identification and Validation of Organic Triazole Based Ligands as Potential Inhibitory Drug Compounds of SARS-CoV-2 Main Protease

Popis výsledku v původním jazyce

The SARS-CoV-2 virus is highly contagious to humans and has caused a pandemic of global proportions. Despite worldwide research efforts, efficient targeted therapies against the virus are still lacking. With the ready availability of the macromolecular structures of coronavirus and its known variants, the search for anti-SARS-CoV-2 therapeutics through in silico analysis has become a highly promising field of research. In this study, we investigate the inhibiting potentialities of triazole-based compounds against the SARS-CoV-2 main protease (M-pro). The SARS-CoV-2 main protease (M-pro) is known to play a prominent role in the processing of polyproteins that are translated from the viral RNA. Compounds were pre-screened from 171 candidates (collected from the DrugBank database). The results showed that four candidates (Bemcentinib, Bisoctrizole, PYIITM, and NIPFC) had high binding affinity values and had the potential to interrupt the main protease (M-pro) activities of the SARS-CoV-2 virus. The pharmacokinetic parameters of these candidates were assessed and through molecular dynamic (MD) simulation their stability, interaction, and conformation were analyzed. In summary, this study identified the most suitable compounds for targeting Mpro, and we recommend using these compounds as potential drug molecules against SARS-CoV-2 after follow up studies.

Název v anglickém jazyce

In Silico Identification and Validation of Organic Triazole Based Ligands as Potential Inhibitory Drug Compounds of SARS-CoV-2 Main Protease

Popis výsledku anglicky

The SARS-CoV-2 virus is highly contagious to humans and has caused a pandemic of global proportions. Despite worldwide research efforts, efficient targeted therapies against the virus are still lacking. With the ready availability of the macromolecular structures of coronavirus and its known variants, the search for anti-SARS-CoV-2 therapeutics through in silico analysis has become a highly promising field of research. In this study, we investigate the inhibiting potentialities of triazole-based compounds against the SARS-CoV-2 main protease (M-pro). The SARS-CoV-2 main protease (M-pro) is known to play a prominent role in the processing of polyproteins that are translated from the viral RNA. Compounds were pre-screened from 171 candidates (collected from the DrugBank database). The results showed that four candidates (Bemcentinib, Bisoctrizole, PYIITM, and NIPFC) had high binding affinity values and had the potential to interrupt the main protease (M-pro) activities of the SARS-CoV-2 virus. The pharmacokinetic parameters of these candidates were assessed and through molecular dynamic (MD) simulation their stability, interaction, and conformation were analyzed. In summary, this study identified the most suitable compounds for targeting Mpro, and we recommend using these compounds as potential drug molecules against SARS-CoV-2 after follow up studies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/ED1.1.00%2F02.0109" target="_blank" >ED1.1.00/02.0109: Biotechnologické a biomedicínské centrum Akademie věd a Univerzity Karlovy</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Molecules

ISSN

1420-3049

e-ISSN

1420-3049

Svazek periodika

26

Číslo periodika v rámci svazku

20

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

15

Strana od-do

6199

Kód UT WoS článku

000716269500001

EID výsledku v databázi Scopus

2-s2.0-85117443189