The Role of Cytochrome P450 Enzymes in COVID-19 Pathogenesis and Therapy

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.