Mujwar Somdutt
Institute of Pharmaceutical Research, GLA University, Mathura, 281406, Uttar Pradesh, India.
Comput Biol Med. 2021 Sep;136:104748. doi: 10.1016/j.compbiomed.2021.104748. Epub 2021 Aug 8.
The outbreak of the triple mutant strain of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) was more virulent and pathogenic than its original strain. The viral triple mutant strain of SARS-COV-2 is extremely adaptive and increases penetrability into the host. The triple mutant viral strain was first reported in Brazil and South Africa and then communicated to different countries responsible for the second wave of the coronavirus disease (COVID-19) global pandemic with a high mortality rate. The reported genomic mutations are responsible for the alterations in the viral functional and structural proteins, causing the ineffectiveness of the existing antiviral therapy targeting these proteins. Thus, in current research, molecular docking simulation-based virtual screening of a ligand library consisting of FDA-approved existing drugs followed by molecular dynamics simulation-based validation of leads was performed to develop a potent inhibitor molecule for the triple mutant viral strain SARS-CoV-2. Based on the safety profile, tamibarotene was selected as a safe and effective drug candidate for developing therapy against the triple mutant viral spike protein of SARS-CoV-2.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的三重突变株的爆发比其原始毒株更具毒性和致病性。SARS-CoV-2的病毒三重突变株具有极强的适应性，并增加了对宿主的穿透性。该三重突变病毒株首先在巴西和南非被报道，然后传播到不同国家，引发了第二波死亡率很高的冠状病毒病（COVID-19）全球大流行。报告的基因组突变导致病毒功能和结构蛋白发生改变，致使针对这些蛋白的现有抗病毒疗法失效。因此，在当前研究中，进行了基于分子对接模拟的虚拟筛选，该筛选针对由美国食品药品监督管理局（FDA）批准的现有药物组成的配体库，随后基于分子动力学模拟对先导化合物进行验证，以开发一种针对三重突变病毒株SARS-CoV-2的有效抑制剂分子。基于安全性概况，他米巴罗汀被选为开发针对SARS-CoV-2三重突变病毒刺突蛋白疗法的安全有效候选药物。
