Berbamine inhibits the infection of SARS-CoV-2 and flaviviruses by compromising TPRMLs-mediated endolysosomal trafficking of viral receptors [post]

Lihong Huang, Huanan Li, Terrence Tsz-Tai Yuen, Zuodong Ye, Qiang Fu, Wei Sun, Qiang Xu, Yang Yang, Jasper Fuk-Woo Chan, Guoliang Zhang, Hin Chu, Wenbao Qi (+1 others)
2020 unpublished
Positive-sense single-stranded ((+)ss) RNA viruses are among the leading causes of human and animal infectious diseases in the world, but so far, no effective antiviral agents are available to treat these infections. Here we found that several bis- benzylisoquinoline alkaloids (e.g. berbamine), potently inhibited the infection of coronaviruses (e.g. SARS-CoV-2 and MERS-CoV), flaviviruses (e.g. JEV, ZIKV and DENV), and enteroviruses (e.g. EV-A71) in host cells. Moreover, berbamine protected mice
more » ... mine protected mice from lethal challenge of JEV. We also found that berbamine inhibited TRPMLs (Ca2+ permeable non-selective cation channels in endosomes and lysosomes), which compromised the endolysosomal trafficking of viral receptors, such as ACE2 and DPP4. This led to the increased secretion of these receptors via extracellular vesicles and the concomitant decrease in their levels at the plasma membrane, thereby preventing (+)ss RNA viruses from entering the host cells. In summary, these results indicate that bis- benzylisoquinoline alkaloids such as berbamine, can act as a pan-anti-(+)ss RNA virus drug by inhibiting TPRMLs to prevent viral entry.
doi:10.21203/rs.3.rs-30922/v1 fatcat:on4fprd6rvg3bketiv5ht2id3u