Identification of novel potential ricin inhibitors by virtual screening, molecular docking, molecular dynamics and MM-PBSA calculations: a drug repurposing approach

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F22%3A50017703" target="_blank" >RIV/62690094:18470/22:50017703 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.tandfonline.com/doi/abs/10.1080/07391102.2020.1870154?journalCode=tbsd20" target="_blank" >https://www.tandfonline.com/doi/abs/10.1080/07391102.2020.1870154?journalCode=tbsd20</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07391102.2020.1870154" target="_blank" >10.1080/07391102.2020.1870154</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Identification of novel potential ricin inhibitors by virtual screening, molecular docking, molecular dynamics and MM-PBSA calculations: a drug repurposing approach

Popis výsledku v původním jazyce

Ricin is a potent cytotoxin with no available antidote. Its catalytic subunit, RTA, damages the ribosomal RNA (rRNA) of eukaryotic cells, preventing protein synthesis and eventually leading to cell death. The combination between easiness of obtention and high toxicity turns ricin into a potential weapon for terrorist attacks, urging the need of discovering effective antidotes. On this context, we used computational techniques, in order to identify potential ricin inhibitors among approved drugs. Two libraries were screened by two different docking algorithms, followed by molecular dynamics simulations and MM-PBSA calculations in order to corroborate the docking results. Three drugs were identified as potential ricin inhibitors: deferoxamine, leucovorin and plazomicin. Our calculations showed that these compounds were able to, simultaneously, form hydrogen bonds with residues of the catalytic site and the secondary binding site of RTA, qualifying as potential antidotes against intoxication by ricin.

Název v anglickém jazyce

Identification of novel potential ricin inhibitors by virtual screening, molecular docking, molecular dynamics and MM-PBSA calculations: a drug repurposing approach

Popis výsledku anglicky

Ricin is a potent cytotoxin with no available antidote. Its catalytic subunit, RTA, damages the ribosomal RNA (rRNA) of eukaryotic cells, preventing protein synthesis and eventually leading to cell death. The combination between easiness of obtention and high toxicity turns ricin into a potential weapon for terrorist attacks, urging the need of discovering effective antidotes. On this context, we used computational techniques, in order to identify potential ricin inhibitors among approved drugs. Two libraries were screened by two different docking algorithms, followed by molecular dynamics simulations and MM-PBSA calculations in order to corroborate the docking results. Three drugs were identified as potential ricin inhibitors: deferoxamine, leucovorin and plazomicin. Our calculations showed that these compounds were able to, simultaneously, form hydrogen bonds with residues of the catalytic site and the secondary binding site of RTA, qualifying as potential antidotes against intoxication by ricin.

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

2022

Kód důvěrnosti údajů

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

Název periodika

Journal of biomolecular structure and dynamics

ISSN

0739-1102

e-ISSN

1538-0254

Svazek periodika

40

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

5309-5319

Kód UT WoS článku

000605432400001

EID výsledku v databázi Scopus

2-s2.0-85099174647