Abstract
Coronavirus disease 2019 (COVID-19) has become a new public health crisis threatening the world. Dysregulated immune responses are the most striking pathophysiological features of patients with severe COVID-19, which can result in multiple-organ failure and death. The cytochrome P450 (CYP) system is the most important drug metabolizing enzyme family, which plays a significant role in the metabolism of endogenous or exogenous substances. Endogenous CYPs participate in the biosynthesis or catabolism of endogenous substances, including steroids, vitamins, eicosanoids, and fatty acids, whilst xenobiotic CYPs are associated with the metabolism of environmental toxins, drugs, and carcinogens. CYP expression and activity are greatly affected by immune response. However, changes in CYP expression and/or function in COVID-19 and their impact on COVID-19 pathophysiology and the metabolism of therapeutic agents in COVID-19, remain unclear. In this analysis, we review current evidence predominantly in the following areas: firstly, the possible changes in CYP expression and/or function in COVID-19; secondly, the effects of CYPs on the metabolism of arachidonic acid, vitamins, and steroid hormones in COVID-19; and thirdly, the effects of CYPs on the metabolism of therapeutic COVID-19 drugs.
Highlights
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global challenge
Numerous previous studies showed cytochrome P450 (CYP) played a role in lung injury, kidney injury and liver injury, including CYPs we mentioned above that may affected in COVID-19, suggesting these CYPs may be involved in the pathophysiological process of severe COVID-19
As the most common drug metabolizing enzyme family, CYPs are closely related to the metabolism of endogenous and exogenous substances
Summary
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global challenge. Numerous SARS-CoV-2 variants have been detected around the world. Many SARS-CoV-2 variants are more infectious than original wild strain, which have brought new challenges to the prevention and control of COVID-19 (Tian et al, 2021). Dysregulated immune response, cytokine storm, is a prominent feature of COVID-19, which can result in multiple-organ failure and death. CYP expression and activity are greatly affected by immune mediators, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1, and interferon (IFN)-γ. Changes in CYP expression and/or function in COVID-19 and their impact on its pathophysiology, and on the metabolism of therapeutic agents in COVID-19. This review focuses on the involvement of CYPs in the pathophysiology and pharmacotherapeutics of COVID-19
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