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

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

doi:10.3389/fphar.2022.835136

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

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

Authors

Mohitosh Biswas^{1

2

3}, Nares Sawajan^{1

2

4}, Thanyada Rungrotmongkol^{5

6}, Kamonpan Sanachai⁵, Maliheh Ershadian^{1

2}, Chonlaphat Sukasem^{1

2

7

8}

Affiliations

¹ Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
² Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
³ Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.
⁴ Department of Pathology, School of Medicine, Mae Fah Luang University, Chiang Rai, Thailand.
⁵ Structural and Computational Biology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
⁶ Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, Thailand.
⁷ Pharmacogenomics and Precision Medicine, The Preventive Genomics and Family Check-up Services Center, Bumrungrad International Hospital, Bangkok, Thailand.
⁸ MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

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

Keywords: COVID-19; drug-drug interactions; drug-herb interactions; molecular docking; pathogenesis and severity; pharmacogenetics; precision medicine; repurposed drugs.

Publication types

Review