Molecular modeling study of natural products as potential bioactive compounds against SARS-CoV-2

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F23%3A50020441" target="_blank" >RIV/62690094:18470/23:50020441 - isvavai.cz</a>

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s00894-023-05586-5" target="_blank" >https://link.springer.com/article/10.1007/s00894-023-05586-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00894-023-05586-5" target="_blank" >10.1007/s00894-023-05586-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Molecular modeling study of natural products as potential bioactive compounds against SARS-CoV-2

Popis výsledku v původním jazyce

Context: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 infection and responsible for millions of victims worldwide, remains a significant threat to public health. Even after the development of vaccines, research interest in the emergence of new variants is still prominent. Currently, the focus is on the search for effective and safe drugs, given the limitations and side effects observed for the synthetic drugs administered so far. In this sense, bioactive natural products that are widely used in the pharmaceutical industry due to their effectiveness and low toxicity have emerged as potential options in the search for safe drugs against COVID-19. Following this line, we screened 10 bioactive compounds derived from cholesterol for molecules capable of interacting with the receptor-binding domain (RBD) of the spike protein from SARS-CoV-2 (SC2Spike), responsible for the virus’s invasion of human cells. Rounds of docking followed by molecular dynamics simulations and binding energy calculations enabled the selection of three compounds worth being experimentally evaluated against SARS-CoV-2. Methods: The 3D structures of the cholesterol derivatives were prepared and optimized using the Spartan 08 software with the semi-empirical method PM3. They were then exported to the Molegro Virtual Docking (MVD®) software, where they were docked onto the RBD of a 3D structure of the SC2Spike protein that was imported from the Protein Data Bank (PDB). The best poses obtained from MVD® were subjected to rounds of molecular dynamics simulations using the GROMACS software, with the OPLS/AA force field. Frames from the MD simulation trajectories were used to calculate the ligand’s free binding energies using the molecular mechanics – Poisson-Boltzmann surface area (MM-PBSA) method. All results were analyzed using the xmgrace and Visual Molecular Dynamics (VMD) software. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Název v anglickém jazyce

Molecular modeling study of natural products as potential bioactive compounds against SARS-CoV-2

Popis výsledku anglicky

Context: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 infection and responsible for millions of victims worldwide, remains a significant threat to public health. Even after the development of vaccines, research interest in the emergence of new variants is still prominent. Currently, the focus is on the search for effective and safe drugs, given the limitations and side effects observed for the synthetic drugs administered so far. In this sense, bioactive natural products that are widely used in the pharmaceutical industry due to their effectiveness and low toxicity have emerged as potential options in the search for safe drugs against COVID-19. Following this line, we screened 10 bioactive compounds derived from cholesterol for molecules capable of interacting with the receptor-binding domain (RBD) of the spike protein from SARS-CoV-2 (SC2Spike), responsible for the virus’s invasion of human cells. Rounds of docking followed by molecular dynamics simulations and binding energy calculations enabled the selection of three compounds worth being experimentally evaluated against SARS-CoV-2. Methods: The 3D structures of the cholesterol derivatives were prepared and optimized using the Spartan 08 software with the semi-empirical method PM3. They were then exported to the Molegro Virtual Docking (MVD®) software, where they were docked onto the RBD of a 3D structure of the SC2Spike protein that was imported from the Protein Data Bank (PDB). The best poses obtained from MVD® were subjected to rounds of molecular dynamics simulations using the GROMACS software, with the OPLS/AA force field. Frames from the MD simulation trajectories were used to calculate the ligand’s free binding energies using the molecular mechanics – Poisson-Boltzmann surface area (MM-PBSA) method. All results were analyzed using the xmgrace and Visual Molecular Dynamics (VMD) software. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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

2023

Kód důvěrnosti údajů

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

Název periodika

Journal of Molecular Modeling

ISSN

1610-2940

e-ISSN

0948-5023

Svazek periodika

29

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

"Article number: 183"

Kód UT WoS článku

000992796900001

EID výsledku v databázi Scopus

2-s2.0-85159758419