In silico studies of potential selective inhibitors of thymidylate kinase from variola virus

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F21%3A50018474" target="_blank" >RIV/62690094:18470/21:50018474 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11150/21:10435245 RIV/00179906:_____/21:10435245

Výsledek na webu

<a href="https://www.mdpi.com/1424-8247/14/10/1027" target="_blank" >https://www.mdpi.com/1424-8247/14/10/1027</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ph14101027" target="_blank" >10.3390/ph14101027</a>

Jazyk výsledku

angličtina

Název v původním jazyce

In silico studies of potential selective inhibitors of thymidylate kinase from variola virus

Popis výsledku v původním jazyce

Continuing the work developed by our research group, in the present manuscript, we per-formed a theoretical study of 10 new structures derived from the antivirals cidofovir and ribavirin, as inhibitor prototypes for the enzyme thymidylate kinase from Variola virus (VarTMPK). The proposed structures were subjected to docking calculations, molecular dynamics simulations, and free energy calculations, using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method, in-side the active sites of VarTMPK and human TMPK (HssTMPK). The docking and molecular dynamic studies pointed to structures 2, 3, 4, 6, and 9 as more selective towards VarTMPK. In addition, the free energy data calculated through the MM-PBSA method, corroborated these results. This suggests that these compounds are potential selective inhibitors of VarTMPK and, thus, can be considered as template molecules to be synthesized and experimentally evaluated against smallpox. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Název v anglickém jazyce

In silico studies of potential selective inhibitors of thymidylate kinase from variola virus

Popis výsledku anglicky

Continuing the work developed by our research group, in the present manuscript, we per-formed a theoretical study of 10 new structures derived from the antivirals cidofovir and ribavirin, as inhibitor prototypes for the enzyme thymidylate kinase from Variola virus (VarTMPK). The proposed structures were subjected to docking calculations, molecular dynamics simulations, and free energy calculations, using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method, in-side the active sites of VarTMPK and human TMPK (HssTMPK). The docking and molecular dynamic studies pointed to structures 2, 3, 4, 6, and 9 as more selective towards VarTMPK. In addition, the free energy data calculated through the MM-PBSA method, corroborated these results. This suggests that these compounds are potential selective inhibitors of VarTMPK and, thus, can be considered as template molecules to be synthesized and experimentally evaluated against smallpox. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

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

Pharmaceuticals

ISSN

1424-8247

e-ISSN

—

Svazek periodika

14

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

16

Strana od-do

"Article number: 1027"

Kód UT WoS článku

000726388100001

EID výsledku v databázi Scopus

2-s2.0-85117309908