Department of Chemical Engineering, University of New Hampshire, Durham, New Hampshire, USA.
Department of Molecular, Cellular, and Biomedical Services, University of New Hampshire, Durham, New Hampshire, USA.
Proteins. 2022 Nov;90(11):1896-1907. doi: 10.1002/prot.26385. Epub 2022 Jun 3.
We report molecular interactions and inhibition of the main protease (M ) of SARS-CoV-2, a key enzyme involved in the viral life cycle. By using a thiadiazolidinone (TDZD) derivative as a chemical probe, we explore the conformational dynamics of M via docking protocols and molecular dynamics simulations in all-atom detail. We reveal the local and global dynamics of M in the presence of this inhibitor and confirm the inhibition of the enzyme with an IC value of 1.39 ± 0.22 μM, which is comparable to other known inhibitors of this enzyme.
我们报告了 SARS-CoV-2 的主要蛋白酶（M ）的分子相互作用和抑制，该酶是病毒生命周期中涉及的关键酶。我们使用噻二唑烷酮（TDZD）衍生物作为化学探针，通过对接方案和全原子细节的分子动力学模拟来探索 M 的构象动力学。我们揭示了在存在这种抑制剂的情况下 M 的局部和整体动力学，并证实了该酶的抑制作用，其 IC 值为 1.39±0.22μM，与该酶的其他已知抑制剂相当。
