We used qRT-PCR and chromogenic immunohistochemistry to investigate the impact of SARS-CoV-2 infection on the expression of 25 clinically relevant drug metabolizing enzymes and membrane transporters (DMETs) using Vero E6 cells and postmortem COVID-19 human lung tissues. Results revealed dysregulation of CYP3A4 and UGT1A1 mRNA expression, as well as P-gp and MRP1 protein expression in SARS-CoV-2 infected Vero E6 cells and postmortem COVID-19 human lung tissues, respectively. We uncovered the novel pulmonary localization of 13 DMETs in control and COVID-19 postmortem human lung tissues and showed that inflammatory response is the major factor driving the discrepancy in localization. We observed that SARS-CoV-2 infection, inflammatory markers, xenosensing regulatory proteins, DMETs are localized in the same pulmonary alveolar epithelial cells and lymphocytes. These findings suggest that SARS-CoV-2 infection can lead to interindividual differences in drug response, highlighting the need for personalized treatment strategies for COVID-19 patients, especially those with comorbidities.
Learning Objectives:
Understand how SARS-CoV-2 infection affects the expression of clinically relevant drug processing proteins in Vero E6 cells.
Explore how COVID-19 affects the expression of clinically relevant drug processing proteins in human lung tissues.
Discuss the molecular mechanism underlying the interactions between COVID-19 and clinically relevant drug processing proteins in human lung tissues.
Demonstrate the effect of disease severity on the expression of clinically relevant drug processing proteins in COVID-19 patients
Define the role of personalized treatment strategies for COVID-19 patients, especially those with comorbidities