Rivero-Segura Nadia A, Gomez-Verjan Juan C
Dirección de Investigación, Instituto Nacional de Geriatría, Ciudad de Mexico 10200, Mexico.
Biomolecules. 2021 Feb 4;11(2):216. doi: 10.3390/biom11020216.
The COVID-19 pandemic has already taken the lives of more than 2 million people worldwide, causing several political and socio-economic disturbances in our daily life. At the time of publication, there are non-effective pharmacological treatments, and vaccine distribution represents an important challenge for all countries. In this sense, research for novel molecules becomes essential to develop treatments against the SARS-CoV-2 virus. In this context, Mexican natural products have proven to be quite useful for drug development; therefore, in the present study, we perform an in silico screening of 100 compounds isolated from the most commonly used Mexican plants, against the SARS-CoV-2 virus. As results, we identify ten compounds that meet leadlikeness criteria (emodin anthrone, kaempferol, quercetin, aesculin, cichoriin, luteolin, matricin, riolozatrione, monocaffeoyl tartaric acid, aucubin). According to the docking analysis, only three compounds target the key proteins of SARS-CoV-2 (quercetin, riolozatrione and cichoriin), but only one appears to be safe (cichoriin). ADME (absorption, distribution, metabolism and excretion) properties and the physiologically based pharmacokinetic (PBPK) model show that cichoriin reaches higher lung levels (100 mg/Kg, IV); therefore, it may be considered in developing therapeutic tools.
新冠疫情已在全球夺走了超过200万人的生命，给我们的日常生活带来了诸多政治和社会经济动荡。在本文发表之时，尚无有效的药物治疗方法，疫苗分发对所有国家来说都是一项重大挑战。从这个意义上讲，研发新型分子对于开发针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的治疗方法至关重要。在此背景下，墨西哥的天然产物已被证明对药物开发非常有用；因此，在本研究中，我们对从墨西哥最常用植物中分离出的100种化合物进行了针对SARS-CoV-2病毒的计算机模拟筛选。结果，我们鉴定出了十种符合类先导物标准的化合物（大黄素蒽酮、山奈酚、槲皮素、七叶苷、菊苣酸、木犀草素、母菊天蓝烃、里奥洛扎曲酮、单咖啡酰酒石酸、桃叶珊瑚苷）。根据对接分析，只有三种化合物靶向SARS-CoV-2的关键蛋白（槲皮素、里奥洛扎曲酮和菊苣酸），但只有一种似乎是安全的（菊苣酸）。药物代谢动力学（吸收、分布、代谢和排泄）特性以及基于生理学的药代动力学（PBPK）模型表明，菊苣酸在肺部达到更高水平（100毫克/千克，静脉注射）；因此，在开发治疗工具时可以考虑使用它。
