Antiviral culinary plants are potential bioresources for preventive nutraceuticals and/or antiviral drugs in COVID-19. Structure-based virtual screening was undertaken to screen 173 compounds previously reported from Vernonia amygdalina and Occinum gratissimum for direct interaction with the active site of the 3-Chymotrypsin-Like Protease (3CL^pro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on docking scores and comparison with reference inhibitors, a hit-list of 10 top phytocompounds was defined, which also had strong interactions with the catalytic centre of 3CL^pro from three related strains of coronavirus (SARS-CoV, MERS-CoV, HKU4). Among these, six compounds (neoandrographolide, vernolide, isorhamnetin, chicoric acid, luteolin, and myricetin) exhibited the highest binding tendencies to the equilibrated conformers of SARS-CoV-2 3CL^pro in an in-depth docking analysis to 5 different representative conformations from the cluster analysis of the molecular dynamics simulation (MDS) trajectories of the protein. In silico drug-likeness analyses revealed two drug-like terpenoids viz: neoandrographolide and vernolide as promising inhibitors of SARS-CoV-2 3CL^pro. These structures were accommodated within the substrate-binding pocket; and interacted with the catalytic dyad (Cys¹⁴⁵ and His⁴¹), the oxyanion loop (residues 138–145), and the S1/S2 sub-sites of the enzyme active site through the formation of an array of hydrogen bonds and hydrophobic interactions. Molecular dynamics simulation and binding free energy calculation revealed that the terpenoid-enzyme complexes exhibit strong interactions and structural stability. Therefore, these compounds may stabilize the conformation of the flexible oxyanion loop; and thereby interfere with the tetrahedral oxyanion intermediate formation during the proteolytic activity of the enzyme.

抗病毒食用植物是 COVID-19 预防性营养保健品和/或抗病毒药物的潜在生物资源。进行了基于结构的虚拟筛选以筛选先前从杏仁斑鸠菊和Occinum gratissimum中报道的 173 种化合物，这些化合物与严重急性呼吸系统综合症冠状病毒 2（SARS- ^CoV- 2). 根据对接分数和与参考抑制剂的比较，确定了 10 种顶级植物化合物的命中列表，这些化合物也与 3CL ^{pro的催化中心有很强的相互作用}来自三种相关的冠状病毒株（SARS-CoV、MERS-CoV、HKU4）。其中，六种化合物（新穿心莲内酯、vernolide、异鼠李素、菊苣酸、木犀草素和杨梅素）在对来自 SARS-CoV-2 3CL pro的 5 种不同代表性构象的深入对接分析中表现出与 SARS-CoV-2 3CL ^pro平衡构象异构体的最高结合倾向蛋白质分子动力学模拟（MDS）轨迹的聚类分析。计算机模拟药物分析揭示了两种类似药物的萜类化合物，即新穿心莲内酯和葎菊内酯，它们是 SARS-CoV-2 3CL ^pro的有前途的抑制剂。这些结构被容纳在底物结合口袋中；并与催化二元体相互作用（Cys ¹⁴⁵和 His ⁴¹)、氧阴离子环（残基 138-145）和酶活性位点的 S1/S2 亚位点，通过形成一系列氢键和疏水相互作用。分子动力学模拟和结合自由能计算表明萜类-酶复合物表现出很强的相互作用和结构稳定性。因此，这些化合物可以稳定柔性氧阴离子环的构象；从而干扰酶的蛋白水解活性过程中四面体氧阴离子中间体的形成。