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Pharmacogenomics and COVID-19: clinical implications of human genome interactions with repurposed drugs.
Pharmacogenomics J. 2021 06; 21(3):275-284.PJ

Abstract

The outbreak of Coronavirus disease 2019 (COVID-19) has evolved into an emergent global pandemic. Many drugs without established efficacy are being used to treat COVID-19 patients either as an offlabel/compassionate use or as a clinical trial. Although drug repurposing is an attractive approach with reduced time and cost, there is a need to make predictions on success before the start of therapy. For the optimum use of these repurposed drugs, many factors should be considered such as drug-gene or dug-drug interactions, drug toxicity, and patient co-morbidity. There is limited data on the pharmacogenomics of these agents and this may constitute an obstacle for successful COVID-19 therapy. This article reviewed the available human genome interactions with some promising repurposed drugs for COVID-19 management. These drugs include chloroquine (CQ), hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir (LPV/r), atazanavir (ATV), favipiravir (FVP), nevirapine (NVP), efavirenz (EFV), oseltamivir, remdesivir, anakinra, tocilizumab (TCZ), eculizumab, heme oxygenase 1 (HO-1) regulators, renin-angiotensin-aldosterone system (RAAS) inhibitors, ivermectin, and nitazoxanide. Drug-gene variant pairs that may alter the therapeutic outcomes in COVID-19 patients are presented. The major drug variant pairs that associated with variations in clinical efficacy include CQ/HCQ (CYP2C8, CYP2D6, ACE2, and HO-1); azithromycin (ABCB1); LPV/r (SLCO1B1, ABCB1, ABCC2 and CYP3A); NVP (ABCC10); oseltamivir (CES1 and ABCB1); remdesivir (CYP2C8, CYP2D6, CYP3A4, and OATP1B1); anakinra (IL-1a); and TCZ (IL6R and FCGR3A). The major drug variant pairs that associated with variations in adverse effects include CQ/HCQ (G6PD; hemolysis and ABCA4; retinopathy), ATV (MDR1 and UGT1A1*28; hyperbilirubinemia; and APOA5; dyslipidemia), NVP (HLA-DRB1*01, HLA-B*3505 and CYP2B6; skin rash and MDR1; hepatotoxicity), and EFV (CYP2B6; depression and suicidal tendencies).

Authors+Show Affiliations

Clinical Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, Egypt. osama.badary@bue.edu.eg. Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. osama.badary@bue.edu.eg.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

33542445

Citation

Badary, Osama A.. "Pharmacogenomics and COVID-19: Clinical Implications of Human Genome Interactions With Repurposed Drugs." The Pharmacogenomics Journal, vol. 21, no. 3, 2021, pp. 275-284.
Badary OA. Pharmacogenomics and COVID-19: clinical implications of human genome interactions with repurposed drugs. Pharmacogenomics J. 2021;21(3):275-284.
Badary, O. A. (2021). Pharmacogenomics and COVID-19: clinical implications of human genome interactions with repurposed drugs. The Pharmacogenomics Journal, 21(3), 275-284. https://doi.org/10.1038/s41397-021-00209-9
Badary OA. Pharmacogenomics and COVID-19: Clinical Implications of Human Genome Interactions With Repurposed Drugs. Pharmacogenomics J. 2021;21(3):275-284. PubMed PMID: 33542445.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacogenomics and COVID-19: clinical implications of human genome interactions with repurposed drugs. A1 - Badary,Osama A, Y1 - 2021/02/04/ PY - 2020/06/13/received PY - 2021/01/15/accepted PY - 2020/12/07/revised PY - 2021/2/6/pubmed PY - 2021/6/9/medline PY - 2021/2/5/entrez SP - 275 EP - 284 JF - The pharmacogenomics journal JO - Pharmacogenomics J VL - 21 IS - 3 N2 - The outbreak of Coronavirus disease 2019 (COVID-19) has evolved into an emergent global pandemic. Many drugs without established efficacy are being used to treat COVID-19 patients either as an offlabel/compassionate use or as a clinical trial. Although drug repurposing is an attractive approach with reduced time and cost, there is a need to make predictions on success before the start of therapy. For the optimum use of these repurposed drugs, many factors should be considered such as drug-gene or dug-drug interactions, drug toxicity, and patient co-morbidity. There is limited data on the pharmacogenomics of these agents and this may constitute an obstacle for successful COVID-19 therapy. This article reviewed the available human genome interactions with some promising repurposed drugs for COVID-19 management. These drugs include chloroquine (CQ), hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir (LPV/r), atazanavir (ATV), favipiravir (FVP), nevirapine (NVP), efavirenz (EFV), oseltamivir, remdesivir, anakinra, tocilizumab (TCZ), eculizumab, heme oxygenase 1 (HO-1) regulators, renin-angiotensin-aldosterone system (RAAS) inhibitors, ivermectin, and nitazoxanide. Drug-gene variant pairs that may alter the therapeutic outcomes in COVID-19 patients are presented. The major drug variant pairs that associated with variations in clinical efficacy include CQ/HCQ (CYP2C8, CYP2D6, ACE2, and HO-1); azithromycin (ABCB1); LPV/r (SLCO1B1, ABCB1, ABCC2 and CYP3A); NVP (ABCC10); oseltamivir (CES1 and ABCB1); remdesivir (CYP2C8, CYP2D6, CYP3A4, and OATP1B1); anakinra (IL-1a); and TCZ (IL6R and FCGR3A). The major drug variant pairs that associated with variations in adverse effects include CQ/HCQ (G6PD; hemolysis and ABCA4; retinopathy), ATV (MDR1 and UGT1A1*28; hyperbilirubinemia; and APOA5; dyslipidemia), NVP (HLA-DRB1*01, HLA-B*3505 and CYP2B6; skin rash and MDR1; hepatotoxicity), and EFV (CYP2B6; depression and suicidal tendencies). SN - 1473-1150 UR - https://www.unboundmedicine.com/medline/citation/33542445/Pharmacogenomics_and_COVID-19:_clinical_implications_of_human_genome_interactions_with_repurposed_drugs. L2 - https://doi.org/10.1038/s41397-021-00209-9 DB - PRIME DP - Unbound Medicine ER -
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