ArticleFrontiers in pharmacology2023
SARS-CoV-2 infection dysregulates the expression of clinically relevant drug metabolizing enzymes in Vero E6 cells and membrane transporters in human lung tissues.
Article in Frontiers in pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- The role of ivermectin in the prevention and treatment of SARS-CoV-2 infection: a meta-analysis of randomized controlled trials.BMC infectious diseases · 2026Pooled it
- Toxicity and DNA Adduct Formation Reinforce AI-Guided Prediction of Aflatoxin B1 Bioactivation in VERO E6 Cells.Toxins · 2026Article
- Severe acute respiratory syndrome coronavirus 2-mediated dysregulation of drug processing genes is dependent on pathogenic variants, target site of infection, age, and sex.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- COVID-19 Alters Inflammatory, Mitochondrial, and Protein Clearance Pathway Genes: Potential Implications for New-onset Parkinsonism in Patients.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Analysis of the Protective Effects ofNutrients · 2024Article
- Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections.Viruses · 2024Article
- Mirvetuximab soravtansine in ovarian cancer therapy: expert opinion on pharmacological considerations.Cancer chemotherapy and pharmacology · 2024Review
- High and Low Levels ofInternational journal of molecular sciences · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2-mediated interactions with drug metabolizing enzymes and membrane transporters (DMETs) in different tissues, especially lung, the main affected organ may limit the clinical efficacy and safety profile of promising COVID-19 drugs. Herein, we investigated whether SARS-CoV-2 infection could dysregulate the expression of 25 clinically relevant DMETs in Vero E6 cells and postmortem lung tissues from COVID-19 patients. Also, we assessed the role of 2 inflammatory and 4 regulatory proteins in modulating the dysregulation of DMETs in human lung tissues. We showed for the first time that SARS-CoV-2 infection dysregulates CYP3A4 and UGT1A1 at the mRNA level, as well as P-gp and MRP1 at the protein level, in Vero E6 cells and postmortem human lung tissues, respectively. We observed that at the cellular level, DMETs could potentially be dysregulated by SARS-CoV-2-associated inflammatory response and lung injury. We uncovered the pulmonary cellular localization of CYP1A2, CYP2C8, CYP2C9, and CYP2D6, as well as ENT1 and ENT2 in human lung tissues, and observed that the presence of inflammatory cells is the major driving force for the discrepancy in the localization of DMETs between COVID-19 and control human lung tissues. Because alveolar epithelial cells and lymphocytes are both sites of SARS-CoV-2 infection and localization of DMETs, we recommend further investigation of the pulmonary pharmacokinetic profile of current COVID-19 drug dosing regimen to improve clinical outcomes.
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