Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Elini St., Cairo, 11562, Egypt; Medicinal Chemistry Department, Faculty of Pharmacy, King Salman International University, Ras-Sedr, South Sinai, Egypt.
Pharmacognosy Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt.
Virology. 2022 May;570:18-28. doi: 10.1016/j.virol.2022.03.003. Epub 2022 Mar 22.
The challenge continues globally triggered by the absence of an approved antiviral drug against COVID-19 virus infection necessitating global concerted efforts of scientists. Nature still provides a renewable source for drugs used to solve many health problems. The aim of this work is to provide new candidates from natural origin to overcome COVID-19 pandemic. A virtual screening of the natural compounds database (47,645 compounds) using structure-based pharmacophore model and molecular docking simulations reported eight hits from natural origin against SARS-CoV-2 main proteinase (Mpro) enzyme. The successful candidates were of terpenoidal nature including taxusabietane, Isoadenolin A & C, Xerophilusin B, Excisanin H, Macrocalin B and ponicidin, phytoconstituents isolated from family Lamiaceae and sharing a common ent-kaurane nucleus, were found to be the most successful candidates. This study suggested that the diterpene nucleus has a clear positive contribution which can represent a new opportunity in the development of SARS-CoV-2 main protease inhibitors.
由于缺乏针对 COVID-19 病毒感染的批准抗病毒药物，这一挑战在全球范围内持续存在，需要科学家们全球协同努力。大自然仍然为用于解决许多健康问题的药物提供了可再生的资源。这项工作的目的是提供来自天然来源的新候选药物，以克服 COVID-19 大流行。使用基于结构的药效团模型和分子对接模拟对天然化合物数据库（47645 种化合物）进行虚拟筛选，针对 SARS-CoV-2 主要蛋白酶（Mpro）酶，从天然来源中发现了 8 种命中物。成功的候选物具有萜类性质，包括 Taxusabietane、Isoadenolin A 和 C、Xerophilusin B、Excisanin H、Macrocalin B 和 Ponicidin，它们是从唇形科植物中分离出来的植物成分，具有共同的 ent-kaurane 核，被认为是最成功的候选物。这项研究表明，二萜核具有明显的积极贡献，这可能为开发 SARS-CoV-2 主要蛋白酶抑制剂提供新的机会。
