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用于改善新冠病毒疾病治疗的药物遗传学和精准医学方法。

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies.

作者信息

Biswas Mohitosh, Sawajan Nares, Rungrotmongkol Thanyada, Sanachai Kamonpan, Ershadian Maliheh, Sukasem Chonlaphat

机构信息

Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.

出版信息

Front Pharmacol. 2022 Feb 18;13:835136. doi: 10.3389/fphar.2022.835136. eCollection 2022.

DOI:10.3389/fphar.2022.835136
PMID:35250581
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8894812/
Abstract

Many drugs are being administered to tackle coronavirus disease 2019 (COVID-19) pandemic situations without establishing clinical effectiveness or tailoring safety. A repurposing strategy might be more effective and successful if pharmacogenetic interventions are being considered in future clinical studies/trials. Although it is very unlikely that there are almost no pharmacogenetic data for COVID-19 drugs, however, from inferring the pharmacokinetic (PK)/pharmacodynamic(PD) properties and some pharmacogenetic evidence in other diseases/clinical conditions, it is highly likely that pharmacogenetic associations are also feasible in at least some COVID-19 drugs. We strongly mandate to undertake a pharmacogenetic assessment for at least these drug-gene pairs (atazanavir-, , , ; efavirenz-; nevirapine-, , ; lopinavir-, ; ribavirin-; tocilizumab-; ivermectin-; oseltamivir-, ; clopidogrel-, , warfarin-, ; non-steroidal anti-inflammatory drugs (NSAIDs)-) in COVID-19 patients for advancing precision medicine. Molecular docking and computational studies are promising to achieve new therapeutics against SARS-CoV-2 infection. The current situation in the discovery of anti-SARS-CoV-2 agents at four important targets from studies has been described and summarized in this review. Although natural occurring compounds from different herbs against SARS-CoV-2 infection are favorable, however, accurate experimental investigation of these compounds is warranted to provide insightful information. Moreover, clinical considerations of drug-drug interactions (DDIs) and drug-herb interactions (DHIs) of the existing repurposed drugs along with pharmacogenetic (e.g., efavirenz and ) and herbogenetic (e.g., andrographolide and ) interventions, collectively called multifactorial drug-gene interactions (DGIs), may further accelerate the development of precision COVID-19 therapies in the real-world clinical settings.

摘要

许多药物在未确立临床疗效或未进行安全性调整的情况下就被用于应对2019冠状病毒病(COVID-19)大流行情况。如果在未来的临床研究/试验中考虑药物遗传学干预,药物重新利用策略可能会更有效且成功。尽管COVID-19药物几乎没有药物遗传学数据的可能性极小,然而,从推断其他疾病/临床状况中的药代动力学(PK)/药效学(PD)特性及一些药物遗传学证据来看,至少在某些COVID-19药物中,药物遗传学关联也很可能是可行的。我们强烈要求至少对这些药物-基因对(阿扎那韦-,,,;依非韦伦-;奈韦拉平-,,;洛匹那韦-;利巴韦林-;托珠单抗-;伊维菌素-;奥司他韦-;氯吡格雷-,,华法林-;非甾体抗炎药(NSAIDs)-)在COVID-19患者中进行药物遗传学评估,以推进精准医学。分子对接和计算研究有望实现针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的新疗法。本综述描述并总结了来自研究的四个重要靶点的抗SARS-CoV-2药物发现的现状。尽管来自不同草药的天然化合物对SARS-CoV-2感染有利,但对这些化合物进行准确的实验研究以提供有见地的信息是必要的。此外,现有重新利用药物的药物-药物相互作用(DDIs)和药物-草药相互作用(DHIs)的临床考虑,连同药物遗传学(如依非韦伦和)和草药遗传学(如穿心莲内酯和)干预,统称为多因素药物-基因相互作用(DGIs),可能会在真实世界临床环境中进一步加速精准COVID-19疗法的发展。

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