The present pandemic situation due to coronavirus has led to the search for newer prevention, diagnostic, and treatment methods. The onset of the corona infection in a human results in acute respiratory illness followed by death if not diagnosed and treated with suitable antiretroviral drugs. With the unavailability of the targeted drug treatment, several repurposed drugs are being used for treatment. However, the side-effects of the drugs urges us to move to a search for newer synthetic- or phytochemical-based drugs. The present study investigates the use of various phytochemicals virtually screened from various plant sources in Western Ghats, India, and subsequently molecular docking studies were performed to identify the efficacy of the drug in retroviral infection particularly coronavirus infection. Out of 57 phytochemicals screened initially based on the structural and physicochemical properties, 39 were effectively used for the docking analysis. Finally, 5 lead compounds with highest hydrophobic interaction and number of H-bonds were screened. Results from the interaction analysis suggest Piperolactam A to be pocketed well with good hydrophobic interaction with the residues in the binding region R1. ADME and toxicity profiling also reveals Piperolactam A with higher LogS values indicating higher permeation and hydrophilicity. Toxicity profiling suggests that the 5 screened compounds to be relatively safe. The in silico methods used in this study suggests that the compound Piperolactam A to be the most effective inhibitor of S-protein from binding to the GRP78 receptor. By blocking the binding of the S-protein to the CS-GRP78 cell surface receptor, they can inhibit the binding of the virus to the host.

中文翻译：

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虚拟筛选植物化学化合物作为 SARS-CoV-2 感染的潜在抑制剂

目前由冠状病毒引起的大流行情况导致人们寻找更新的预防、诊断和治疗方法。如果不进行诊断和使用合适的抗逆转录病毒药物治疗，人类感染冠状病毒会导致急性呼吸系统疾病，然后死亡。由于无法进行靶向药物治疗，因此正在使用几种重新利用的药物进行治疗。然而，药物的副作用促使我们转向寻找新的合成或植物化学药物。本研究调查了从印度西高止山脉的各种植物来源中虚拟筛选的各种植物化学物质的使用，随后进行了分子对接研究，以确定该药物在逆转录病毒感染特别是冠状病毒感染中的功效。在最初根据结构和物理化学性质筛选的 57 种植物化学物质中，有 39 种有效地用于对接分析。最后，筛选出具有最高疏水相互作用和 H 键数量的 5 种先导化合物。相互作用分析的结果表明哌内酰胺 A 与结合区 R1 中的残基具有良好的疏水相互作用。ADME 和毒性分析还显示哌内酰胺 A 具有较高的 LogS 值，表明较高的渗透性和亲水性。毒性分析表明，5 种筛选化合物相对安全。本研究中使用的计算机方法表明化合物哌内酰胺 A 是最有效的 S 蛋白与 GRP78 受体结合的抑制剂。