Potent and Specific Inhibition of NTCP-Mediated HBV/HDV Infection and Substrate Transporting by a Novel, Oral-Available Cyclosporine A Analogue

Analogues
of the natural product cyclosporine A (CsA) were developed
and assessed as antivirals against infection of hepatitis B virus
(HBV) and its satellite hepatitis D virus (HDV). An analogue termed 27A exhibits potent inhibition of HBV/HDV infection by specifically
blocking viral engagement to its cellular receptor NTCP, while it
lacks immunosuppressive activity found in natural CsA. Intraperitoneal
injection or oral intake of 27A protects HDV-susceptible
mouse model from HDV infection. 27A serves as a promising
lead for the development of novel anti-HDV/HBV agents.