喷昔洛韦抑制 SARS-CoV-2 机制的检测：分子动力学研究。

Inspection on the Mechanism of SARS-CoV-2 Inhibition by Penciclovir: A Molecular Dynamic Study.

机构信息

Department of Chemical Science and Technologies, University of Rome "Tor Vergata", Via della Ricerca Scientifica, 00133 Rome, Italy.

出版信息

Molecules. 2022 Dec 26;28(1):191. doi: 10.3390/molecules28010191.

In recent years, humanity has had to face a critical pandemic due to SARS-CoV-2. In the rapid search for effective drugs against this RNA-positive virus, the repurposing of already existing nucleotide/nucleoside analogs able to stop RNA replication by inhibiting the RNA-dependent RNA polymerase enzyme has been evaluated. In this process, a valid contribution has been the use of in silico experiments, which allow for a rapid evaluation of the possible effectiveness of the proposed drugs. Here we propose a molecular dynamic study to provide insight into the inhibition mechanism of Penciclovir, a nucleotide analog on the RNA-dependent RNA polymerase enzyme. Besides the presented results, in this article, for the first time, molecular dynamic simulations have been performed considering not only the RNA-dependent RNA polymerase protein, but also its cofactors (fundamental for RNA replication) and double-strand RNA.

近年来，由于 SARS-CoV-2，人类不得不面对一场严重的大流行病。在快速寻找针对这种 RNA 阳性病毒的有效药物的过程中，评估了重新利用已经存在的核苷酸/核苷类似物，这些类似物可以通过抑制 RNA 依赖性 RNA 聚合酶酶来阻止 RNA 复制。在这个过程中，使用计算实验提供了有效的帮助，这使得可以快速评估所提出药物的可能有效性。在这里，我们提出了一项分子动力学研究，旨在深入了解喷昔洛韦（一种核苷酸类似物）对 RNA 依赖性 RNA 聚合酶酶的抑制机制。除了呈现的结果外，在本文中，首次进行了分子动力学模拟，不仅考虑了 RNA 依赖性 RNA 聚合酶蛋白，还考虑了其辅助因子（RNA 复制的基础）和双链 RNA。