Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of COVID-19 Spike pseudotype virus

BackgroundCOVID-19 has been affecting global health since the end of 2019 and so far, no any sign shows the relief of the pandemic. The major issue for controlling the infection disease is lacking efficient prevention and therapeutic approaches. Chloroquine (CQ) and Hydroxychloroquine (HCQ) has been reported to treat the disease, but underlying mechanism still keeps controversial. Purpose: The objective of this study was to investigate whether CQ and HCQ could be an ACE2 blocker to inhibit COVID-19 infection.MethodsIn our study, we used CCK-8 stain, flow cytometry and immunofluorescent stain to evaluated the toxicity and autophagy of CQ and HCQ respectively on ACE2 high expressed HEK293T cells (ACE2h cells). We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking, surface plasmon resonance (SPR) assays and molecule docking, and COVID-19 spike pseudotype virus was also used to observe the viropexis effect of CQ and HCQ in ACEh cells.ResultsResults showed that HCQ is slightly more toxic to ACE2h cells than CQ, both CQ and HCQ could bind to ACE2 with KD (7.31±0.62)e-7 and (4.82±0.87)e-7, respectively. They also exhibit equivalent suppression effect for the entrance of COVID-19 spike pseudotype virus into ACE2h cells.ConclusionsCQ and HCQ both inhibite the entrance COVID-19 virus into cell by blocking the binding of the virus with ACE2. Our finding provides a novel insight into the molecular mechanism of CQ and HCQ treatment effect on the virus infection.