Botelho, Fernanda D; Santos, Marcelo C; da Silva Goncalves, Arlan; Franca, Tanos Celmar Costa; Laplante, Steven 
ORCID: https://orcid.org/0000-0003-2835-5789 et de Almeida, Joyce S F D
(2021).
Identification of novel potential ricin inhibitors by virtual screening, molecular docking, molecular dynamics and MM-PBSA calculations: a drug repurposing approach
Journal of Biomolecular Structure and Dynamics
.
DOI: 10.1080/07391102.2020.1870154.
(Sous Presse)
Résumé
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. Communicated by Ramaswamy H. Sarma.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | Ricin Inhibitors; Biological Warfare Agents; Drug Repurposing; Ricin; Virtual Screening |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 22 juin 2022 19:18 |
| Dernière modification: | 07 nov. 2022 16:53 |
| URI: | https://espace.inrs.ca/id/eprint/12305 |
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