Higher Medical & Biological School, Laboratory of Computational Modeling of Drugs, South Ural State University, Chelyabinsk, Chelyabinsk, Russia.
Department of Medicinal Chemistry, University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia.
PeerJ. 2022 Jun 2;10:e13374. doi: 10.7717/peerj.13374. eCollection 2022.
Exploring potent herbal medicine candidates is a promising strategy for combating a pandemic in the present global health crisis. In Ayurveda (a traditional medicine system in India), (WS) is one of the most important herbs and it has been used for millennia as Rasayana (a type of juice) for its wide-ranging health benefits. WS phytocompounds display a broad spectrum of biological activities (such as antioxidant, anticancer and antimicrobial) modulate detoxifying enzymes, and enhance immunity. Inspired by the numerous biological actions of WS phytocompounds, the present investigation explored the potential of the WS phytocompounds against the SARS-CoV-2 main protease (3CL). We selected 11 specific withanolide compounds, such as withaphysalin, withasomniferol, and withafastuosin, through manual literature curation against 3CL. A molecular similarity analysis showed their similarity with compounds that have an established inhibitory activity against the SARS-CoV-2. molecular docking and molecular dynamics simulations elucidated withasomniferol C (WS11) as a potential candidate against SARS-CoV-2 3CL. Additionally, the present work also presents a new method of validating docking poses using the AlteQ method.
探索有效的草药候选物是应对当前全球健康危机大流行的一种有前途的策略。在印度传统医学体系阿育吠陀中，（WS）是最重要的草药之一，几千年来一直被用作 Rasayana（一种果汁），因其广泛的健康益处而备受推崇。WS 植物化合物具有广泛的生物活性（如抗氧化、抗癌和抗菌），可调节解毒酶，增强免疫力。受 WS 植物化合物众多生物学作用的启发，本研究探讨了 WS 植物化合物对 SARS-CoV-2 主要蛋白酶（3CL）的潜在作用。我们通过手动文献整理，针对 3CL 选择了 11 种特定的醉茄内酯化合物，如醉茄素、醉茄苷和醉茄呋甾醇。分子相似性分析表明，它们与具有抗 SARS-CoV-2 活性的化合物具有相似性。分子对接和分子动力学模拟表明，醉茄素 C（WS11）是一种针对 SARS-CoV-2 3CL 的潜在候选药物。此外，本工作还提出了一种使用 AlteQ 方法验证对接构象的新方法。
