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

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

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.835136

DOI=10.3389/fphar.2022.835136

ISSN=1663-9812

ABSTRACT=<p>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–<italic>UGT1A1</italic>, <italic>ABCB1</italic>, <italic>SLCO1B1</italic>, <italic>APOA5</italic>; efavirenz–<italic>CYP2B6</italic>; nevirapine–<italic>HLA</italic>, <italic>CYP2B6</italic>, <italic>ABCB1</italic>; lopinavir–<italic>SLCO1B3</italic>, <italic>ABCC2</italic>; ribavirin–<italic>SLC28A2</italic>; tocilizumab–<italic>FCGR3A</italic>; ivermectin–<italic>ABCB1</italic>; oseltamivir–<italic>CES1</italic>, <italic>ABCB1</italic>; clopidogrel–<italic>CYP2C19</italic>, <italic>ABCB1</italic>, warfarin–<italic>CYP2C9</italic>, <italic>VKORC1</italic>; non-steroidal anti-inflammatory drugs (NSAIDs)–<italic>CYP2C9</italic>) 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 <italic>in silico</italic> 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 <italic>CYP2B6</italic>) and herbogenetic (e.g., andrographolide and <italic>CYP2C9</italic>) interventions, collectively called multifactorial drug–gene interactions (DGIs), may further accelerate the development of precision COVID-19 therapies in the real-world clinical settings.</p>