Pharmacogenetics Approach for the Improvement of COVID-19 Treatment

Fricke-Galindo, Ingrid; Falfán-Valencia, Ramcés

doi:10.3390/v13030413

Cited by 23 publications

(28 citation statements)

References 99 publications

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“…A recent study demonstrated that, like other viral infections, during the progression of COVID-19 local and systemic inflammation as well as the “cytokine storm” will potentially cause downregulation of the major CYP enzymes including CYP3A4 [ 35 ]. A new study proposed that COVID-19 pharmacogenetic studies include CYP3A4 variants [ 36 ]. The [ 33 ] study shows that CYPs metabolic activity will be surely changed during the SARS-CoV-2 infection in a similar manner, resulting in a pharmacokinetic interaction with the recommended drugs for COVID-19 treatments.…”

Section: Resultsmentioning

confidence: 99%

Using informative features in machine learning based method for COVID-19 drug repurposing

2021

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Coronavirus disease 2019 (COVID-19) is caused by a novel virus named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This virus induced a large number of deaths and millions of confirmed cases worldwide, creating a serious danger to public health. However, there are no specific therapies or drugs available for COVID-19 treatment. While new drug discovery is a long process, repurposing available drugs for COVID-19 can help recognize treatments with known clinical profiles. Computational drug repurposing methods can reduce the cost, time, and risk of drug toxicity. In this work, we build a graph as a COVID-19 related biological network. This network is related to virus targets or their associated biological processes. We select essential proteins in the constructed biological network that lead to a major disruption in the network. Our method from these essential proteins chooses 93 proteins related to COVID-19 pathology. Then, we propose multiple informative features based on drug–target and protein−protein interaction information. Through these informative features, we find five appropriate clusters of drugs that contain some candidates as potential COVID-19 treatments. To evaluate our results, we provide statistical and clinical evidence for our candidate drugs. From our proposed candidate drugs, 80% of them were studied in other studies and clinical trials.

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Section: Resultsmentioning

confidence: 99%

Using informative features in machine learning based method for COVID-19 drug repurposing

2021

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“…Ivermectin is also a substrate of P-gp encoded by the ABCB1, and genetic polymorphisms of ABCB1 have linked to severe neurologic ADRs (Lespine et al, 2006;Baudou et al, 2020). Also, ivermectin is transported by the OATP1A2 and OATP2B1 encoded by the SLCO1A2 and SLCO2B1, respectively, although no pharmacogenetic study was identified for this association to date in the literature (Fricke-Galindo and Falfán-Valencia, 2021;Telbisz et al, 2021).…”

Section: Ivermectinmentioning

confidence: 99%

“…The SNP rs71647871 of CES1 has been found to be associated with variation in plasma concentration-time curve of oseltamivir (Tarkiainen et al, 2012) The PK of oseltamivir may also be affected by the ABCB1, CES1, NEU2, and SLC15A1 genetic variants. The SNP rs1045642 of ABCB1 was associated with neurologic ADRs developed by oseltamivir (Bermúdez de León et al, 2020;Fricke-Galindo and Falfán-Valencia, 2021).…”

Section: Oseltamivirmentioning

confidence: 99%

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

et al. 2022

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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.

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“…In another study, the variability in drug responses in COVID-19 patients was evaluated based on pharmacogenetics as a means of improving patient outcomes [ 21 ]. The pharmacogenetics for the treatment of COVID-19 with remdesivir, oseltamivir, lopinavir, ritonavir, azithromycin, chloroquine, HCQ, ivermectin, and dexamethasone was investigated.…”

Section: Clinical Findingsmentioning

confidence: 99%