Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is β-coronavirus that is responsible for the pandemic coronavirus disease 2019 (COVID-19) all over the world. The rapid spread of the novel SARS CoV-2 worldwide is raising a significant global public health issue with nearly 61.86 million people infected and 1.4 million deaths. To date, no specific drugs are available for the treatment of COVID-19. The inhibition of proteases essential for the proteolytic treatment of viral polyproteins is a conventional therapeutic strategy for conquering viral infections. In the study, molecular docking approach was used to screen potential drug compounds among the phytochemicals of Vitex negundo L. against COVID-19 infection. Molecular docking analysis showed that oleanolic acid forms a stable complex and other phyto-compounds ursolic acid, 3β-acetoxyolean-12-en-27-oic acid and isovitexin of V. negundo natural compounds form a less-stable complex. When compared with the control the synergistic interaction of these compounds shows inhibitory activity against papain-like protease (PL^pro) of SARS CoV-2 (COVID-19). The molecular dynamics (MD) simulation (50 ns) were performed on the complexes of PL^pro and the phyto-compounds viz. oleanolic acid, ursolic acid, 3β-acetoxyolean-12-en-27-oic acid and isovitexin followed by the binding free energy calculations using MM-GBSA and these molecules have stable interactions with PL^pro protein binding site. The MD simulation study provides more insight into the functional properties of the protein-ligand complex and suggests that these molecules can be considered as a potential drug molecule against COVID-19. In this pandemic situation, these herbal compounds provide a rich resource to produce new antivirals against COVID-19.

Communicated by Ramaswamy H. Sarma

摘要

严重急性呼吸系统综合症冠状病毒 2 (SARS CoV-2) 是一种 β 冠状病毒，它是全球流行的 2019 年冠状病毒病 (COVID-19) 的罪魁祸首。新型 SARS CoV-2 在全球范围内的迅速传播正在引发一个重大的全球公共卫生问题，近 6186 万人被感染，140 万人死亡。迄今为止，尚无特定药物可用于治疗 COVID-19。抑制对病毒多蛋白进行蛋白水解处理所必需的蛋白酶是克服病毒感染的常规治疗策略。本研究采用分子对接的方法在荆条的植物化学物质中筛选潜在的药物化合物。L. 抗 COVID-19 感染。分子对接分析表明齐墩果酸形成稳定的复合物，而其他植物化合物熊果酸、3β-acetoxyolean-12-en-27-oic 酸和V. negundo天然化合物的异牡荆素形成不太稳定的复合物。与对照相比，这些化合物的协同相互作用显示出对SARS CoV-2 (COVID-19) 的木瓜蛋白酶 (PL ^{pro ) 的抑制活性。}分子动力学 (MD) 模拟 (50 ns) 对 PL ^pro和植物化合物即. 齐墩果酸、熊果酸、3β-acetoxyolean-12-en-27-oic 酸和异牡荆素，然后使用 MM-GBSA 计算结合自由能，这些分子与 PL 具有稳定的相互作用^pro蛋白结合位点。MD 模拟研究更深入地了解了蛋白质-配体复合物的功能特性，并表明这些分子可以被视为一种潜在的抗 COVID-19 药物分子。在这种大流行的情况下，这些草药化合物提供了丰富的资源来生产针对 COVID-19 的新抗病毒药物。

由 Ramaswamy H. Sarma 传达