Potent and Specific Inhibition of NTCP-Mediated HBV/HDV Infection and Substrate Transporting by a Novel, Oral-Available Cyclosporine A Analogue
Yang Liu, Hanying Ruan, Ying Li, Guoliang Sun, Xiao Liu, Wenhui He, Fengfeng Mao, Miaomiao He, Liwei Yan, Guocai Zhong, Huan Yan, Wenhui Li, Zhiyuan Zhang
Abstract
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.
Topics & Concepts
VirologyHepatitis D virusHepatitis B virusNatural productVirusChemistryHepatitis DBiologyStereochemistryHBsAgHepatitis B Virus StudiesHepatitis C virus researchHepatitis Viruses Studies and Epidemiology