Rahman Mohammad Rejaur, Banik Anik, Chowdhury Ishtiak Malique, Sajib Emran Hossain, Sarkar Sanchita
Department of Molecular Biology & Genetic Engineering, Sylhet Agricultural University, Sylhet, Bangladesh.
Faculty of Biotechnology & Genetic Engineering, Sylhet Agricultural University, Sylhet, Bangladesh.
Inform Med Unlocked. 2021;23:100531. doi: 10.1016/j.imu.2021.100531. Epub 2021 Feb 10.
SARS-CoV-2 has triggered a major epidemic among people around the world, and it is the newest in the sequence to become prevalent among other infectious diseases. The drug repurposing concept has been utilized effectively for numerous viral infections. Considering the situation and the urgency, the idea of drug repurposing for coronavirus infection (COVID-19) is also being studied. The molecular docking method was used for the screening of 29 antiviral drugs against primary protease proteins (MPP) of SARS-CoV-2, spike ecto-domain, spike receptor binding domain, Nsp9 RNA binding protein, and HR2 domain. Among these drugs, in terms of least binding energy, Indinavir, Sorivudine, Cidofovir, and Darunavir showed minimum docking scores with all the key proteins. For ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) analysis, the ADMET properties of the top 4 drug candidates were retrieved through literature study. This analysis revealed that these drug candidates are well metabolized, distributed, and bioavailable, but have some undesirable effects. Furthermore, some approved structural analogues, such as Telbivudine, Tenofovir, Amprenavir, Fosamprenavir, etc., were predicted as similar drugs which may also be used for treating viral infections. We highly recommend these drug candidates as potential fighters against the deadly SARS-CoV-2 virus, and suggest in vivo trials for experimental validation of our findings.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)在全球引发了一场大流行,它是众多传染病中最新流行起来的一种。药物重新利用的概念已在多种病毒感染中得到有效应用。鉴于当前形势和紧迫性,针对冠状病毒感染(COVID-19)进行药物重新利用的想法也正在研究中。分子对接方法被用于筛选29种抗SARS-CoV-2主要蛋白酶蛋白(MPP)、刺突胞外结构域、刺突受体结合结构域、Nsp9 RNA结合蛋白和HR2结构域的抗病毒药物。在这些药物中,就最低结合能而言,茚地那韦、索立夫定、西多福韦和达芦那韦与所有关键蛋白的对接分数最低。对于药物代谢动力学(吸收、分布、代谢、排泄和毒性)分析,通过文献研究获取了前4种候选药物的药物代谢动力学特性。该分析表明,这些候选药物具有良好的代谢、分布和生物利用度,但存在一些不良影响。此外,一些已获批的结构类似物,如替比夫定、替诺福韦、安普那韦、福沙普那韦等,被预测为可能也用于治疗病毒感染的类似药物。我们强烈推荐这些候选药物作为对抗致命SARS-CoV-2病毒的潜在药物,并建议进行体内试验以对我们的研究结果进行实验验证。