Abstract

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

摘要

蓖麻毒素是一种有效的细胞毒素，没有可用的解毒剂。它的催化亚基RTA破坏真核细胞的核糖体RNA（rRNA），阻止蛋白质合成并最终导致细胞死亡。易于获得和高毒性之间的结合使蓖麻毒蛋白成为恐怖袭击的潜在武器，因此迫切需要发现有效的解毒剂。在这种情况下，我们使用了计算技术，以便在批准的药物中确定潜在的蓖麻毒蛋白抑制剂。通过两种不同的对接算法筛选了两个文库，随后进行了分子动力学模拟和MM-PBSA计算，以证实对接结果。三种药物被确认为潜在的蓖麻毒素抑制剂：去铁胺，亚叶酸钙和吡唑米星。我们的计算表明，这些化合物能够同时

由Ramaswamy H.Sarma沟通