Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Noida Uttar Pradesh, India.
PLoS One. 2020 Oct 1;15(10):e0240004. doi: 10.1371/journal.pone.0240004. eCollection 2020.
The SARS-CoV-2 virus has caused a pandemic and is public health emergency of international concern. As of now, no registered therapies are available for treatment of coronavirus infection. The viral infection depends on the attachment of spike (S) glycoprotein to human cell receptor angiotensin-converting enzyme 2 (ACE2). We have designed a protein inhibitor (ΔABP-D25Y) targeting S protein using computational approach. The inhibitor consists of two α helical peptides homologues to protease domain (PD) of ACE2. Docking studies and molecular dynamic simulation revealed that the inhibitor binds exclusively at the ACE2 binding site of S protein. The computed binding affinity of the inhibitor is higher than the ACE2 and thus will likely out compete ACE2 for binding to S protein. Hence, the proposed inhibitor ΔABP-D25Y could be a potential blocker of S protein and receptor binding domain (RBD) attachment.
严重急性呼吸系统综合征冠状病毒 2 型（SARS-CoV-2）引发的疫情已构成国际关注的突发公共卫生事件。目前，尚无针对冠状病毒感染的注册治疗方法。病毒感染依赖于刺突（S）糖蛋白与人类细胞受体血管紧张素转化酶 2（ACE2）的结合。我们使用计算方法设计了一种针对 S 蛋白的蛋白抑制剂（ΔABP-D25Y）。该抑制剂由两个与 ACE2 的蛋白酶结构域（PD）同源的α螺旋肽组成。对接研究和分子动力学模拟表明，抑制剂专门结合在 S 蛋白的 ACE2 结合位点。抑制剂的计算结合亲和力高于 ACE2，因此可能会与 ACE2 竞争与 S 蛋白结合。因此，所提出的抑制剂 ΔABP-D25Y 可能是 S 蛋白和受体结合域（RBD）附着的潜在阻滞剂。
