SARS-CoV-2 is the causative agent of COVID-19 and has been declared as pandemic disease by World Health Organization. Lack of targeted therapeutics and vaccines for COVID-2019 have triggered the scientific community to develop new vaccines or drugs against this novel virus. Many synthetic compounds and antimalarial drugs are undergoing clinical trials. The traditional medical practitioners widely use Indian medicinal plant Withania somnifera (Ashwagandha) natural constituents, called withanolides for curing various diseases. The main protease (M^pro) of SARS-CoV-2 plays a vital role in disease propagation by processing the polyproteins which are required for its replication. Hence, it denotes a significant target for drug discovery. In the present study, we evaluate the potential of 40 natural chemical constituents of Ashwagandha to explore a possible inhibitor against main protease of SARS-CoV-2 by adopting the computational approach. The docking study revealed that four constituents of Ashwagandha; Withanoside II (-11.30 Kcal/mol), Withanoside IV (-11.02 Kcal/mol), Withanoside V (-8.96 Kcal/mol) and Sitoindoside IX (-8.37 Kcal/mol) exhibited the highest docking energy among the selected natural constituents. Further, MD simulation study of 100 ns predicts Withanoside V possess strong binding affinity and hydrogen-bonding interactions with the protein active site and indicates its stability in the active site. The binding free energy score also correlates with the highest score of −87.01 ± 5.01 Kcal/mol as compared to other selected compounds. In conclusion, our study suggests that Withanoside V in Ashwagandha may be serve as a potential inhibitor against M^pro of SARS-CoV-2 to combat COVID-19 and may have an antiviral effect on nCoV.

Communicated by Ramaswamy H. Sarma

SARS-CoV-2是COVID-19的病原体，已被世界卫生组织宣布为大流行性疾病。缺乏针对COVID-2019的靶向疗法和疫苗已经触发了科学界开发针对这种新型病毒的新疫苗或药物。许多合成化合物和抗疟药正在接受临床试验。传统医学从业人员广泛使用印度药用植物Withania somnifera（Ashwagandha）的天然成分，称为withanolides来治疗各种疾病。主要蛋白酶（M ^proSARS-CoV-2通过加工复制所需的多蛋白在疾病传播中起着至关重要的作用。因此，它代表了药物发现的重要目标。在本研究中，我们评估了Ashwagandha的40种天然化学成分的潜力，通过采用计算方法来探索可能的抗SARS-CoV-2主要蛋白酶的抑制剂。对接研究表明，Ashwagandha的四个成分。Withanoside II（-11.30 Kcal / mol），Withanoside IV（-11.02 Kcal / mol），Withanoside V（-8.96 Kcal / mol）和Sitoindoside IX（-8.37 Kcal / mol）在选定的天然成分中表现出最高的对接能。进一步，100 ns的MD模拟研究预测Withanoside V与蛋白活性位点具有强结合亲和力和氢键相互作用，并表明其在活性位点的稳定性。与其他选定的化合物相比，结合自由能得分也与−87.01±5.01 Kcal / mol的最高得分相关。总之，我们的研究表明，Ashwagandha中的Withanoside V可能是M的潜在抑制剂^亲SARS-COV-2的作战COVID-19，并可能对nCoV抗病毒作用。

由Ramaswamy H.Sarma沟通