Structure-based discovery of thiosemicarbazones as SARS-CoV-2 main protease inhibitors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00574796" target="_blank" >RIV/61388963:_____/23:00574796 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.4155/fmc-2023-0034" target="_blank" >https://doi.org/10.4155/fmc-2023-0034</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4155/fmc-2023-0034" target="_blank" >10.4155/fmc-2023-0034</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structure-based discovery of thiosemicarbazones as SARS-CoV-2 main protease inhibitors

Popis výsledku v původním jazyce

Aim: Discovery of novel SARS-CoV-2 main protease (Mpro) inhibitors using a structure-based drug discovery strategy. Materials & methods: Virtual screening employing covalent and noncovalent docking was performed to discover Mpro inhibitors, which were subsequently evaluated in biochemical and cellular assays. Results: 91 virtual hits were selected for biochemical assays, and four were confirmed as reversible inhibitors of SARS CoV-2 Mpro with IC50 values of 0.4–3 μM. They were also shown to inhibit SARS-CoV-1 Mpro and human cathepsin L. Molecular dynamics simulations indicated the stability of the Mpro inhibitor complexes and the interaction of ligands at the subsites. Conclusion: This approach led to the discovery of novel thiosemicarbazones as potent SARS-CoV-2 Mpro inhibitors.

Název v anglickém jazyce

Structure-based discovery of thiosemicarbazones as SARS-CoV-2 main protease inhibitors

Popis výsledku anglicky

Aim: Discovery of novel SARS-CoV-2 main protease (Mpro) inhibitors using a structure-based drug discovery strategy. Materials & methods: Virtual screening employing covalent and noncovalent docking was performed to discover Mpro inhibitors, which were subsequently evaluated in biochemical and cellular assays. Results: 91 virtual hits were selected for biochemical assays, and four were confirmed as reversible inhibitors of SARS CoV-2 Mpro with IC50 values of 0.4–3 μM. They were also shown to inhibit SARS-CoV-1 Mpro and human cathepsin L. Molecular dynamics simulations indicated the stability of the Mpro inhibitor complexes and the interaction of ligands at the subsites. Conclusion: This approach led to the discovery of novel thiosemicarbazones as potent SARS-CoV-2 Mpro inhibitors.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Future Medicinal Chemistry

ISSN

1756-8919

e-ISSN

1756-8927

Svazek periodika

15

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

27

Strana od-do

959-985

Kód UT WoS článku

001024699400001

EID výsledku v databázi Scopus

2-s2.0-85168222207