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

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.

p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics)

“…These genes are highly polymorphic (e.g. CYP3A4/5 , CYP2B6 , CYP2C8 , CYP2C9 , CYP2C19 , CYP2D6 ) and are characterized by a wide geographic variability ( Zhou et al, 2017 ; Biswas et al, 2020 ; Sukprasong et al, 2021 ) interacting with large part of those drugs specifically used in COVID-19 ( Sukasem et al, 2013 ; Biswas et al, 2022 ). Interestingly, many clinical complications of COVID-19 belong to the same group of comorbidities responsible for the poor prognosis, and drugs acting as anti-inflammatory, antithrombotic (anti-coagulant and anti-aggregant), anti-hypertensive or with lipid-lowering action, have marked pharmacogenomics features resembling those belonging to the lipoproteins and homocysteine homeostasis genes ( Parmeggiani et al, 2008 ; Gemmati et al, 2009 ; Gemmati et al, 2016 ; Tisato et al, 2019 ; Cappadona et al, 2021 ; Tisato et al, 2021 ; Biswas et al, 2022 ).…”

Disentangling the common genetic architecture and causality of rheumatoid arthritis and systemic lupus erythematosus with COVID-19 outcomes: genome-wide cross trait analysis and bi-directional Mendelian randomization study

“…43 CRHR1, gene of receptor binding, is associated with the efficacy of corticosteroids. 44 Consistently, an open-label randomized controlled trial showed that taking dexamethasone, a corticosteroid, may lower the risk of 28-day mortality by 17% COVID-19-hospitalized patients. 45 Our bi-directional Mendelian randomization study adds to the limited evidence on the causal relationship between RA and COVID-19.…”

In vitro high-content tissue models to address precision medicine challenges

“…One initiative that potentially could facilitate and promote the use of precision medicine towards tackling COVID-19 is the creation of the open-access database named the COVID-19 Genomics and Precision Health database (COVID-19 GPH) by the Genomics and Precision Public Health at the CDC, providing important information such as pathogenic information and the contribution of genomics ( Yu et al, 2022 ). To date, current COVID-19 therapeutics have never undergone multifactorial drug-gene interactions; within this framework, it has been suggested that these therapeutics should undergo evaluation for their genetic associations of relevant metabolic or transporter genes, which would allow for the evaluation of their safety and effectiveness and also promoting precision COVID-19 therapeutics ( Biswas et al, 2022 ). Another strategy that has been investigated in personalized medicine for COVID-19 patients is the use of autologous peripheral blood stem cells and plasma ( Balzanelli et al, 2022 ).…”