Important Pharmacogenetic Information for Drugs Prescribed During the SARS‐CoV‐2 Infection (COVID‐19)

Zubiaur, Pablo; Koller, Dóra; Saiz‐Rodríguez, Miriam; Navares‐Gómez, Marcos; Abad‐Santos, Francisco

doi:10.1111/cts.12866

Cited by 12 publications

(27 citation statements)

References 104 publications

(197 reference statements)

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“…Several pharmacogenetic biomarkers related to the metabolic pathway of drugs used for COVID-19 treatment have been described in the present review. In agreement with previous reports [ 7 , 8 , 9 ], there are variants in CYP2C8 , CYP2D6 , CYP3A4 , CYP3A5 , SLCO2B1 , ABCB1 , ABCC2 , CES1 , and G6PD that could help to improve the clinical outcome of the COVID-19. The scientific evidence supports the study of variants in CYP2D6, CYP3A4 , SLCO2B1 , ABCB1, and ABCC2 with the response to specific drugs ( Figure 2 ).…”

Section: Discussionsupporting

confidence: 92%

“…In this sense, pharmacogenetics could explain the inter-individual variability on drug response based on the genetic of COVID-19 patients [ 6 ]. Variants in genes encoding drug-metabolizing enzymes, transporters, or receptors have been reported, and they could provide the insight to achieve a personalized therapy leading to a better outcome of this emerged disease ( Figure 1 ) [ 7 , 8 , 9 ]; nevertheless, several disease-related issues must be carefully reviewed in the pharmacogenetic study of COVID-19 treatment. Therefore, we aimed to describe the pharmacogenetic variants reported for drugs used for COVID-19 treatment.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacogenetics Approach for the Improvement of COVID-19 Treatment

Fricke-Galindo

Falfán-Valencia

2021

Viruses

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The treatment of coronavirus disease 2019 (COVID-19) has been a challenge. The efficacy of several drugs has been evaluated and variability in drug response has been observed. Pharmacogenetics could explain this variation and improve patients’ outcomes with this complex disease; nevertheless, several disease-related issues must be carefully reviewed in the pharmacogenetic study of COVID-19 treatment. We aimed to describe the pharmacogenetic variants reported for drugs used for COVID-19 treatment (remdesivir, oseltamivir, lopinavir, ritonavir, azithromycin, chloroquine, hydroxychloroquine, ivermectin, and dexamethasone). In addition, other factors relevant to the design of pharmacogenetic studies were mentioned. Variants in CYP3A4, CYP3A5, CYP2C8, CY2D6, ABCB1, ABCC2, and SLCO1B1, among other variants, could be included in pharmacogenetic studies of COVID-19 treatment. Besides, nongenetic factors such as drug–drug interactions and inflammation should be considered in the search for personalized therapy of COVID-19.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics Approach for the Improvement of COVID-19 Treatment

Fricke-Galindo

Falfán-Valencia

2021

Viruses

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“…The new pandemic coronavirus disease 2019 (COVID- 19) is caused by the novel Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is currently triggering enormous global demands on health systems and presents an unprecedented challenge to identify effective drugs for prevention and treatment [1].…”

Section: Covid-19 Backgroundmentioning

confidence: 99%

“…Therefore, the purpose of this review is to look at some drugs commonly used in regimens for COVID-19 and provides specific examples of how genetics may affect drug efficacy and toxicity. It adds to the efforts of recently published relevant articles [18][19][20] and does not serve as an exhaustive review of all relationships between host genetics and these drugs.…”

Section: Covid-19 Therapymentioning

confidence: 99%

Pharmacogenomics and COVID-19: clinical implications of human genome interactions with repurposed drugs

Badary

2021

Pharmacogenomics J

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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).

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“…Many of the investigational repurposed drugs have clinical pharmacogenetic guidelines available, with therapeutic recommendations indicated on the drug label 8 . Atazanavir and fluvoxami,ne for example, include both pharmacogenetics information and prescription recommendations.…”

Section: Introductionmentioning

confidence: 99%

Exploration of interethnic variation and repurposed drug efficacy in the treatment of SARS-CoV-2 Infection (COVID-19)

Aa¹

2021

Preprint

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The COVID-19 global pandemic has led to repurposing of drugs, with little underlying evidence for treatment safety and efficacy. This may increase complications for patients with acute viral respiratory infections. UGT1A1 and CYP2D6 enzymes are involved in the metabolism of atazanavir and fluvoxamine repurposed for COVID-19. This study aimed to elucidate the role of interethnic variation in these enzymes in the efficacy of repurposed drug therapies. A retrospective cohort of 101 Jordanian Arab samples were genotyped using Affymetrix DMET Plus Premier Package. Comprehensive global population genetic structure analyses were performed for CYP2D6 and UGT1A1 allele frequencies across multi-ethnic populations of over 131,000 global subjects from 417 published reports, revealing that Jordanian Arabs share the closest sequence homology to European and Near East populations. The East Asian populations have significantly over-representaiton of individuals with diplotype pairs for reduced atazanavir metabolism compared to the African populations and are more likely to show impaired UGT1A1 metabolism. East Asian populations are also 4.4x more likely to show impaired fluvoxamine metabolism than South Central Asian and Oceanian populations, and 8x more likely than other ancestry populations. The results here support previous findings that interethnic variation should be used for developing proper population-specific dosage guidelines.

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Important Pharmacogenetic Information for Drugs Prescribed During the SARS‐CoV‐2 Infection (COVID‐19)

Cited by 12 publications

References 104 publications

Pharmacogenetics Approach for the Improvement of COVID-19 Treatment

Pharmacogenetics Approach for the Improvement of COVID-19 Treatment

Pharmacogenomics and COVID-19: clinical implications of human genome interactions with repurposed drugs

Exploration of interethnic variation and repurposed drug efficacy in the treatment of SARS-CoV-2 Infection (COVID-19)

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