Pharmacogenomic Landscape of Covid-19 Therapies From Indian Population Genomes

Sahana, Soumitra; Sivadas, Ambily; Mangla, Mohit; Jain, Abhinav; Bhoyar, Rahul C.; Pandhare, Kavita; Mishra, Anushree; Sharma, Disha; Imran, Mohamed; Senthivel, Vigneshwar; Divakar, Mohit Kumar; Rophina, Mercy; Jolly, Bani; Batra, Arushi; Sharma, Sumit; Siwach, Sanjay; Jadhao, Arun G.; Palande, Nikhil V.; Jha, Ganga Nath; Ashrafi, Nishat; Mishra, Prashant; Vidhya, Authiappan; Jain, Suman; Dash, Debasis; Kumar, Nachimuthu Senthil; Vanlallawma, Andrew; Sarma, Ranjan Jyoti; Chhakchhuak, Lalchhandama; Kalyanaraman, Shantaraman; Mahadevan, Radha; Kandasamy, Sunitha; Rajagopal, Raskin Erusan; Ramya, J Ezhil; Devi, P Nirmala; Bajaj, Anjali; Gupta, Vishu; Mathew, Samatha; Goswami, Sangam Giri; Prakash, Savinitha; Joshi, Kandarp; Kumla, Meya; Sreedevi, S; Gajjar, Devarshi; Soraisham, Ronibala; Yadav, Rohit; Devi, Yumnam Silla; Gupta, Aayush; Mukerji, Mitali; Ramalingam, Sivaprakash; Binukumar, B.; Sivasubbu, Sridhar

doi:10.2217/pgs-2021-0028

Cited by 7 publications

(9 citation statements)

References 44 publications

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“…One of the adverse effects which may be avoided by the adjustment of dose and drug based on pharmacogenetics is QT prolongation. Hydroxychloroquine, chloroquine, azithromycin, and lopinavir/ritonavir, as well as some combinations of drug-drug, drug-disease, and drug-gene interactions can individually increase the risk for QT prolongation and torsade de pointes in the course of COVID-19 treatment [162]. In the case of some drugs, the determination of pharmacogenetic markers has already been suggested (listed on the US FDA-recommended drug labels), including the G6PD gene for chloroquine and hydroxychloroquine and IFNL3 for ritonavir.…”

Section: Discussionmentioning

confidence: 99%

Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19?

et al. 2022

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The COVID-19 pandemic is associated with a global health crisis and the greatest challenge for scientists and doctors. The virus causes severe acute respiratory syndrome with an outcome that is fatal in more vulnerable populations. Due to the need to find an efficient treatment in a short time, there were several drugs that were repurposed or repositioned for COVID-19. There are many types of available COVID-19 therapies, including antiviral agents (remdesivir, lopinavir/ritonavir, oseltamivir), antibiotics (azithromycin), antiparasitics (chloroquine, hydroxychloroquine, ivermectin), and corticosteroids (dexamethasone). A combination of antivirals with various mechanisms of action may be more efficient. However, the use of some of these medicines can be related to the occurrence of adverse effects. Some promising drug candidates have been found to be ineffective in clinical trials. The knowledge of pharmacogenetic issues, which translate into variability in drug conversion from prodrug into drug, metabolism as well as transport, could help to predict treatment efficiency and the occurrence of adverse effects in patients. However, many drugs used for the treatment of COVID-19 have not undergone pharmacogenetic studies, perhaps as a result of the lack of time.

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Section: Discussionmentioning

confidence: 99%

Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19?

et al. 2022

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“…Nevertheless, it is a possible extension of our approach that needs to be investigated in future studies. In addition, evaluation of population-specific PGx landscape genetic analysis of the genes proposed as biomarkers is needed that might aid in a better understanding of the inconsistency in therapy response [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Drug genetic associations with COVID-19 manifestations: a data mining and network biology approach

et al. 2022

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Available drugs have been used as an urgent attempt through clinical trials to minimize severe cases of hospitalizations with Coronavirus disease (COVID-19), however, there are limited data on common pharmacogenomics affecting concomitant medications response in patients with comorbidities. To identify the genomic determinants that influence COVID-19 susceptibility, we use a computational, statistical, and network biology approach to analyze relationships of ineffective concomitant medication with an adverse effect on patients. We statistically construct a pharmacogenetic/biomarker network with significant drug-gene interactions originating from gene-disease associations. Investigation of the predicted pharmacogenes encompassing the gene-disease-gene pharmacogenomics (PGx) network suggests that these genes could play a significant role in COVID-19 clinical manifestation due to their association with autoimmune, metabolic, neurological, cardiovascular, and degenerative disorders, some of which have been reported to be crucial comorbidities in a COVID-19 patient.

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“…CYP2C9, CYP1A2, CYP2C8 and CYP3A4 are among the most shared enzymes, linked with approximately 77 COVID-19 drugs, indicating possible interactions upon co-administration [ 95 ]. Inhibitor drugs compete with other substrate drugs to bind with CYPs, leading to an increase of plasma area under the curve (AUC) values and a > 80% decrease in their clearance [ 95 ]. This review focuses on CYP2C9 but it is worth mentioning that some of the drug interactions described in Table 1 are due to induction and inhibition of CYP3A4.…”

Section: Drugs Used To Treat Covid-19mentioning

confidence: 99%

Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions

Lim

Bishtawi

Lim

2023

Eur J Drug Metab Pharmacokinet

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The major human liver drug metabolising cytochrome P450 (CYP) enzymes are downregulated during inflammation and infectious disease state, especially during coronavirus disease 2019 (COVID-19) infection. The influx of proinflammatory cytokines, known as a ‘cytokine storm’, during severe COVID-19 leads to the downregulation of CYPs and triggers new cytokine release, which further dampens CYP expression. Impaired drug metabolism, along with the inevitable co-administration of drugs or ‘combination therapy’ in patients with COVID-19 with various comorbidities, could cause drug–drug interactions, thus worsening the disease condition. Genetic variability or polymorphism in CYP2C9 across different ethnicities could contribute to COVID-19 susceptibility. A number of drugs used in patients with COVID-19 are inducers or inhibitors of, or are metabolised by, CYP2C9, and co-administration might cause pharmacokinetic and pharmacodynamic interactions. It is also worth mentioning that some of the COVID-19 drug interactions are due to altered activity of other CYPs including CYP3A4. Isoniazid/rifampin for COVID-19 and tuberculosis co-infection; lopinavir/ritonavir and cobicistat/remdesivir combination therapy; or multi-drug therapy including ivermectin, azithromycin, montelukast and acetylsalicylic acid, known as TNR4 therapy, all improved recovery in patients with COVID-19. However, a combination of CYP2C9 inducers, inhibitors or both, and plausibly different CYP isoforms could lead to treatment failure, hepatotoxicity or serious side effects including thromboembolism or bleeding, as observed in the combined use of azithromycin/warfarin. Further, herbs that are CYP2C9 inducers and inhibitors, showed anti-COVID-19 properties, and in silico predictions postulated that phytochemical compounds could inhibit SARS-CoV-2 virus particles. COVID-19 vaccines elicit immune responses that activate cytokine release, which in turn suppresses CYP expression that could be the source of compromised CYP2C9 drug metabolism and the subsequent drug–drug interaction. Future studies are recommended to determine CYP regulation in COVID-19, while recognising the involvement of CYP2C9 and possibly utilising CYP2C9 as a target gene to tackle the ever-mutating SARS-CoV-2.

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Pharmacogenomic Landscape of Covid-19 Therapies From Indian Population Genomes

Cited by 7 publications

References 44 publications

Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19?

Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19?

Drug genetic associations with COVID-19 manifestations: a data mining and network biology approach

Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions

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