Abstract

The acute respiratory syndrome caused by the SARS-CoV-2, known as COVID-19, has been ruthlessly tormenting the world population for more than six months. However, so far no effective drug or vaccine against this plague have emerged yet, despite the huge effort in course by researchers and pharmaceutical companies worldwide. Willing to contribute with this fight to defeat COVID-19, we performed a virtual screening study on a library containing Food and Drug Administration (FDA) approved drugs, in a search for molecules capable of hitting three main molecular targets of SARS-CoV-2 currently available in the Protein Data Bank (PDB). Our results were refined with further molecular dynamics (MD) simulations and MM-PBSA calculations and pointed to 7 multi-target hits which we propose here for experimental evaluation and repurposing as potential drugs against COVID-19. Additional rounds of docking, MD simulations and MM-PBSA calculations with remdesivir suggested that this compound can also work as a multi-target drug against SARS-CoV-2.

Communicated by Ramaswamy H. Sarma

摘要

由SARS-CoV-2引起的急性呼吸道综合症，称为COVID-19，已经无情地折磨了全世界六个多月。然而，尽管全球研究人员和制药公司付出了巨大的努力，但迄今为止尚未出现针对这种瘟疫的有效药物或疫苗。愿意为打败COVID-19的斗争做出贡献，我们在一个包含美国食品药品监督管理局（FDA）批准的药物的文库中进行了虚拟筛选研究，以寻找能够击中SARS-CoV-2三个主要分子靶标的分子目前可在蛋白质数据库（PDB）中获得。我们的结果通过进一步的分子动力学（MD）模拟和MM-PBSA计算得到了完善，并指出了7个多目标命中物，我们在这里提出这些命中物用于实验评估，并将其用作针对COVID-19的潜在药物。使用remdesivir的另外几轮对接，MD模拟和MM-PBSA计算表明，该化合物还可以作为针对SARS-CoV-2的多目标药物。

由Ramaswamy H.Sarma沟通