In silico and in vitro evaluation of imatinib as an inhibitor for SARS-CoV-2

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F23%3A00571503" target="_blank" >RIV/60077344:_____/23:00571503 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00027162:_____/23:N0000025

Výsledek na webu

<a href="https://www.tandfonline.com/doi/abs/10.1080/07391102.2022.2045221?journalCode=tbsd20" target="_blank" >https://www.tandfonline.com/doi/abs/10.1080/07391102.2022.2045221?journalCode=tbsd20</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07391102.2022.2045221" target="_blank" >10.1080/07391102.2022.2045221</a>

Jazyk výsledku

angličtina

Název v původním jazyce

In silico and in vitro evaluation of imatinib as an inhibitor for SARS-CoV-2

Popis výsledku v původním jazyce

The rapid geographic expansion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent of Coronavirus Disease 2019 (COVID-19) pandemic, poses an immediate need for potent drugs. Enveloped viruses infect the host cell by cellular membrane fusion, a crucial mechanism required for virus replication. The SARS-CoV-2 spike glycoprotein, due to its primary interaction with the human angiotensin-converting enzyme 2 (ACE2) cell-surface receptor, is considered a potential target for drug development. In this study, around 5,800 molecules were virtually screened using molecular docking. Five molecules were selected for in vitro experiments from those that reported docking scores lower than6 kcal/mol. Imatinib, a Bcr-Abl tyrosine kinase inhibitor, showed maximum antiviral activity in Vero cells. We further investigated the interaction of imatinib, a compound under clinical trials for the treatment of COVID-19, with SARS-CoV-2 RBD, using in silico methods. Molecular dynamics simulations verified that imatinib interacts with RBD residues that are critical for ACE2 binding. This study also provides significant molecular insights on potential repurposable small-molecule drugs and chemical scaffolds for the development of novel drugs targeting the SARS-CoV-2 spike RBD. Communicated by Ramaswamy H. Sarma

Název v anglickém jazyce

In silico and in vitro evaluation of imatinib as an inhibitor for SARS-CoV-2

Popis výsledku anglicky

The rapid geographic expansion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent of Coronavirus Disease 2019 (COVID-19) pandemic, poses an immediate need for potent drugs. Enveloped viruses infect the host cell by cellular membrane fusion, a crucial mechanism required for virus replication. The SARS-CoV-2 spike glycoprotein, due to its primary interaction with the human angiotensin-converting enzyme 2 (ACE2) cell-surface receptor, is considered a potential target for drug development. In this study, around 5,800 molecules were virtually screened using molecular docking. Five molecules were selected for in vitro experiments from those that reported docking scores lower than6 kcal/mol. Imatinib, a Bcr-Abl tyrosine kinase inhibitor, showed maximum antiviral activity in Vero cells. We further investigated the interaction of imatinib, a compound under clinical trials for the treatment of COVID-19, with SARS-CoV-2 RBD, using in silico methods. Molecular dynamics simulations verified that imatinib interacts with RBD residues that are critical for ACE2 binding. This study also provides significant molecular insights on potential repurposable small-molecule drugs and chemical scaffolds for the development of novel drugs targeting the SARS-CoV-2 spike RBD. Communicated by Ramaswamy H. Sarma

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

<a href="/cs/project/NU20-05-00472" target="_blank" >NU20-05-00472: Vývoj nových terapeutik proti viru klíšťové encefalitidy a dalším flavivirům</a><br>

Návaznosti

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

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Journal of Biomolecular Structure & Dynamics

ISSN

0739-1102

e-ISSN

—

Svazek periodika

41

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

3052-3061

Kód UT WoS článku

000761489900001

EID výsledku v databázi Scopus

2-s2.0-85125897415