Dipartimento di Scienze del Farmaco, University of Catania, 95125 Catania, Italy.
Dipartimento di Scienze Biomediche e Biotecnologiche, University of Catania, 95125 Catania, Italy.
Int J Mol Sci. 2020 Aug 14;21(16):5856. doi: 10.3390/ijms21165856.
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a severe global health crisis. In this paper, we used docking and simulation methods to identify potential targets and the mechanism of action of chloroquine (CQ) and hydroxychloroquine (HCQ) against SARS-CoV-2. Our results showed that both CQ and HCQ influenced the functionality of the envelope (E) protein, necessary in the maturation processes of the virus, due to interactions that modify the flexibility of the protein structure. Furthermore, CQ and HCQ also influenced the proofreading and capping of viral RNA in SARS-CoV-2, performed by nsp10/nsp14 and nsp10/nsp16. In particular, HCQ demonstrated a better energy binding with the examined targets compared to CQ, probably due to the hydrogen bonding of the hydroxyl group of HCQ with polar amino acid residues.
严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的迅速传播引发了全球严重的卫生危机。在本文中，我们使用对接和模拟方法来确定氯喹 (CQ) 和羟氯喹 (HCQ) 对 SARS-CoV-2 的潜在作用靶点和作用机制。研究结果表明，CQ 和 HCQ 均通过影响病毒成熟过程中必需的包膜 (E) 蛋白的功能，由于相互作用改变了蛋白质结构的柔韧性。此外，CQ 和 HCQ 还影响了 nsp10/nsp14 和 nsp10/nsp16 对 SARS-CoV-2 病毒 RNA 的校对和加帽作用。特别是，HCQ 与被检测的靶标具有更好的能量结合，这可能是由于 HCQ 的羟基与极性氨基酸残基形成氢键。
