Genetic Profiles in Pharmacogenes Indicate Personalized Drug Therapy for COVID-19

Abstract

Background:The coronavirus disease 2019 has become a global pandemic currently. Many drugs showed potential for COVID-19 therapy. However, genetic factors which can lead to different drug efficiency and toxicity among populations are still undisclosed in COVID-19 therapy. Methods:We selected 67 potential drugs for COVID-19 therapy (DCTs) from clinical guideline and clinical trials databases. 313 pharmaco-genes related to these therapeutic drugs were included. Variation information in 125,748 exomes were collected for racial differences analyses. The expression level of pharmaco-genes in single cell resolution was evaluated from single-cell RNA sequencing (scRNA-seq) data of 17 healthy adults.Results: Pharmacogenes, including CYP3A4, ABCB1, SLCO1B1, ALB, CYP3A5, were involved in the process of more than multi DCTs. 224 potential drug-drug interactions (DDIs) of DCTs were predicted, while 112 of them have been reported.Racial discrepancy of common nonsynonymous mutations was found in pharmacogenes including: VDR, ITPA, G6PD, CYP3A4 and ABCB1 which related to DCTs including ribavirin, α -interferon, chloroquine and lopinavir. Moreover, ACE2, the target of 2019-nCoV, was only found in parts of lung cells, which makes drugs like chloroquine that prevent virus binding to ACE2 more specific than other targeted drugs such as camostat mesylate.

Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations

“…Our study confirmed several findings from the study conducted by Wang et al (58). Mainly, AAF was found to be very high for variants G6PD rs2230037 and ABCB1 rs2032582 in African population.…”

“…To the best of our knowledge, apart from our study, the only study investigating pharmacogenomics landscape of drugs with potential to be used in therapy of COVID-19, taking into account ethnic differences, was reported by Wang and coauthors (58). Sixty-seven potential drugs for COVID-19 was selected from clinical guideline and clinical trials databases and 313 pharmacogenes related to these therapeutics were included.…”

Genetic variants of the human host influencing the coronavirus-associated phenotypes (SARS, MERS and COVID-19): rapid systematic review and field synopsis

“…Preliminary data pointed to germline genetic variants influencing the efficacy of specific therapies administered in patients with COVID-19 [84]. This line of research may disclose basic mechanisms linked to the disease pathophysiology and provide additional hints on the genetic determinants of the host response [85,86].…”

Potential negative effects of the free use of chloroquine to manage COVID‐19 in Colombia

“…Chloroquine phosphate (CQ) stood out among potential personalized pharmacological therapies for COVID‐19 due to the antiviral effect demonstrated in preclinical studies and its high specificity towards the SARS‐CoV‐2 receptor: angiotensin‐converting enzyme 2 (ACE‐2). High distribution within lung tissue (the main organ affected in COVID‐19), 5 and the results described in case series of critically ill COVID‐19 patients with favorable clinical outcomes after being treated with CQ have suggested its possible use as a suitable pharmacological option 6,7 . Based on published evidence, Colombia, China, India, United States, and other countries have included CQ within the management guidelines for COVID‐19 8 or as an extreme measure in patients with a high risk of death.…”