| Literature DB >> 29779957 |
Toby Passioura1, Koichi Watashi2, Kento Fukano3, Satomi Shimura4, Wakana Saso5, Ryo Morishita6, Yuki Ogasawara7, Yasuhito Tanaka8, Masashi Mizokami9, Camille Sureau10, Hiroaki Suga11, Takaji Wakita12.
Abstract
Hepatitis B virus (HBV) constitutes a significant public health burden, and currently available treatment options are not generally curative, necessitating the development of new therapeutics. Here we have applied random non-standard peptide integrated discovery (RaPID) screening to identify small macrocyclic peptide inhibitors of HBV entry that target the cell-surface receptor for HBV, sodium taurocholate cotransporting polypeptide (NTCP). In addition to their anti-HBV activity, these molecules also inhibit cellular entry by the related hepatitis D virus (HDV), and are active against diverse strains of HBV (including clinically relevant nucleos(t)ide analog-resistant and vaccine escaping strains). Importantly, these macrocyclic peptides, in contrast to other NTCP-binding HBV entry inhibitors, exhibited no inhibition of NTCP-mediated bile acid uptake, making them appealing candidates for therapeutic development.Entities:
Keywords: HBV; HDV; NTCP; RaPID; bile acid; cyclosporin; entry; inhibitor; macrocyclic; transporter
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Year: 2018 PMID： 29779957 DOI： 10.1016/j.chembiol.2018.04.011
Source DB: PubMed Journal: Cell Chem Biol ISSN： 2451-9448 Impact factor: 8.116