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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.

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S2286 Cyclosporin A (NSC 290193) Cyclosporin A (Cyclosporine A, Cyclosporine, Ciclosporin, CsA) is an immunosuppressive agent, binds to the cyclophilin and then inhibits calcineurin with IC50 of 7 nM in a cell-free assay, widely used in organ transplantation to prevent rejection. (56) (3)

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