Sethi Aaftaab, Sanam Swetha, Munagalasetty Sharon, Jayanthi Sivaraman, Alvala Mallika
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education & Research-Hyderabad Balanagar India
Computational Drug Design Lab, School of Bio Sciences and Technology, Vellore Institute of Technology Vellore Tamil Nadu India.
RSC Adv. 2020 Aug 13;10(50):29873-29884. doi: 10.1039/d0ra04795c. eCollection 2020 Aug 10.
The Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has been rapidly transmitting and leaving its footprints across the globe. Stringent measures like complete lockdown and extensive testing have been employed by many countries to slow it down in its tracks until a viable treatment is found. Therefore, in the current scenario, prompt solutions need to be uncovered to tackle the virus. In the present study, 330 galectin inhibitors were tested against SARS-CoV-2 spike (S) protein with the aid of molecular docking and molecular dynamics. Finally, the binding free energy and contributing energies were calculated for 2 top scoring ligands by using MM-GBSA method. Many of the galectin inhibitors displayed high binding score against the S protein. They were found to bind to the site of contact of S protein to ACE2. Thus, they show promise of disrupting the ACE2-S protein binding and prevent the virus from invading the host cell. Among the ligands screened, TD-139, a molecule currently in Phase IIb clinical trials, was found to be a potential hit. The present study paves the way for and testing of galectin inhibitors against SARS-CoV-2. In addition, it warrants a swift examination of TD-139 for treating COVID-19.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）一直在全球迅速传播并留下踪迹。许多国家采取了诸如全面封锁和广泛检测等严格措施，以减缓其传播速度，直至找到可行的治疗方法。因此，在当前情况下，需要找到迅速解决办法来应对该病毒。在本研究中，借助分子对接和分子动力学对330种半乳糖凝集素抑制剂进行了针对SARS-CoV-2刺突（S）蛋白的测试。最后，使用MM-GBSA方法计算了2种得分最高的配体的结合自由能和贡献能量。许多半乳糖凝集素抑制剂对S蛋白显示出高结合分数。发现它们与S蛋白与ACE2的接触位点结合。因此，它们有望破坏ACE2-S蛋白的结合并阻止病毒侵入宿主细胞。在筛选出的配体中，目前处于IIb期临床试验的分子TD-139被发现是一个潜在的有效药物。本研究为半乳糖凝集素抑制剂针对SARS-CoV-2的研究和测试铺平了道路。此外，它还需要对TD-139治疗COVID-19进行快速审查。
