EFFECT OF SARS-CoV-2 ON CYTOCHROME P450-DEPENDENT METABOLISM OF DRUG: A REVIEW
DOI:
https://doi.org/10.31861/biosystems2025.02.238Keywords:
virus, liver, COVID-19, cytochrome P450, SARS-CoV-2 infection, xenobioticAbstract
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus that has spread worldwide. In addition to affecting respiratory cells, SARS-CoV-2 also impacts the organs of the digestive system, particularly the liver. It has been established that COVID-19, caused by SARS-CoV-2, significantly affects liver function in infected patients, which is critical for drug pharmacokinetics and safety. SARS-CoV-2 can affect liver cells both directly (via the viral receptor angiotensin-converting enzyme 2 (ACE2)) and indirectly, including through cytokine release and the so-called "cytokine storm." Viral activity leads to elevated liver enzyme levels (ALT, AST, GGT, ALP), decreased albumin levels, and disruption of the metabolism of endogenous substances and xenobiotics. It has been shown that liver injury impairs the function of the system responsible for metabolizing xenobiotics (the monooxygenase system or cytochrome P450 (CYP) system). Dysfunction of the monooxygenase system, in turn, leads to altered drug metabolism and additional toxicity, particularly in cases of drug–drug interactions. This review highlights the main potential mechanisms of liver injury in COVID-19, raising awareness of drug metabolism pathways. Analysis of the metabolism of anti-coronavirus drugs by different CYP isoforms may help prevent drug interactions in patients with comorbidities.
SARS-CoV-2 infection also alters CYP expression, including CYP3A4, CYP2B6, and CYP2C9, via cytokine-mediated regulation, resulting in reduced drug metabolism, increased plasma drug concentrations, and higher risk of toxicity. Polypharmacy in COVID-19, including antiviral drugs, hydroxychloroquine, anti-inflammatory agents, and medications for comorbidities, further increases the risk of drug interactions and liver injury. Anti-cytokine therapy (e.g., tocilizumab) and supportive agents such as melatonin and vitamin D may help restore CYP activity, reduce inflammation, and improve drug clearance. Understanding the mechanisms of SARS-CoV-2-induced liver dysfunction and CYP modulation is essential for optimizing pharmacotherapy, minimizing drug-related toxicity, and improving clinical outcomes in patients with COVID-19.
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