Virtual Screening of Potential AEC2 Inhibitors for COVID-19 from Traditional Chinese Medicine
Abstract Background: Angiotensin-converting enzyme 2 (ACE2), a negative regulator of the renin-angiotensin system and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor, plays an important role in viral genome replication and immune response. ACE2 has been proposed as a potential therapeutic target. Traditional Chinese medicine (TCM) could be considered as a promising complementary therapeutic option in the management of COVID-19. However, the active components and action mechanisms that account for its therapeutic effects remain controversial. Methods: ACE2 was employed as a target related to COVID-19 to explore the active ingredients from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. And the PharmMapper database and TCMSP database were used to predict the targets of the compounds. Moreover, the potential therapeutic targets of COVID-19 were acquired by intersection among genes differentially expressed in COVID-19 patients, genes screened from five public databases and genes targeted by active compounds. Finally, molecular docking verification and function analysis were performed.Results: In this study, puerarin, the common active compound for targeting ACE2 across the five TCMs (Radix Cyathulae, Flos Puerariac, Radix Bupleuri, Radix Puerariac and Radix Hemerocallis), was found. Due to the comprehensive analysis, we revealed that puerarin might prevent the entrance of SARS-CoV-2 entry into cells by blocking ACE2, chiefly modulated the T cell immunity and regulate pro-inflammatory cytokine response by affecting TNF, STAT1 and RNASE3. Conclusion: Taken together, the present study found that puerarin might have a therapeutic effect on COVID-19 through regulation of the immune system, inhibition of inflammation and prevention of virus entry into cells.