De Novo Macrocyclic Peptide Inhibitors of Hepatitis B Virus Cellular Entry

Cell Chemical Biology
Toby PassiouraTakaji Wakita

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.

References

Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·B HagenbuchP J Meier
Mar 5, 2003·The Journal of Experimental Medicine·Birke BartoschFrançois-Loïc Cosset
Jun 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jin ZhongFrancis V Chisari
Jul 15, 2005·Journal of Virology·Azeneth BarreraRobert E Lanford
Sep 29, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Masaya SugiyamaMasashi Mizokami
Nov 10, 2010·Antiviral Therapy·Stephen Locarnini, Fabien Zoulim
Jun 4, 2011·Nature Protocols·Yuki GotoHiroaki Suga
Sep 4, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christopher J HipolitoHiroaki Suga
Oct 9, 2013·Biochemical and Biophysical Research Communications·Syo NakajimaTakaji Wakita
Nov 8, 2013·Pflügers Archiv : European journal of physiology·M Sawkat Anwer, Bruno Stieger
Dec 18, 2013·Biochemical and Biophysical Research Communications·Masashi IwamotoTakaji Wakita
Jan 1, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Koichi WatashiTakaji Wakita
Mar 4, 2014·Annual Review of Biochemistry·Toby PassiouraHiroaki Suga
May 29, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Frédéric M VazRonald J A Wanders
Aug 26, 2014·Biochemical and Biophysical Research Communications·Naoki OguraTakaji Wakita
Nov 25, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Liang PengYiming Wang
Feb 3, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Davor SlijepcevicStan F J van de Graaf
Mar 12, 2015·Nature Communications·Kenichiro ItoHiroaki Suga
Nov 20, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Senko TsukudaTakaji Wakita
Dec 15, 2016·Journal of Hepatology·Eloi R VerrierThomas F Baumert
Apr 7, 2017·Nature Communications·Akane KawamuraChristopher J Schofield
May 26, 2017·Clinical Pharmacology and Therapeutics·A BlankW E Haefeli

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Citations

Jan 5, 2019·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Kento Fukano, Koichi Watashi
Jan 30, 2019·International Journal of Molecular Sciences·Takayuki Katoh, Hiroaki Suga
Jan 30, 2020·The Journal of Infectious Diseases·Panagiota MaraveliaMatti Sällberg
Nov 29, 2020·Scientific Reports·Yingfang LiMasamichi Muramatsu
Nov 28, 2019·Journal of Medicinal Chemistry·Wesley WangChristopher G Parker
Jan 30, 2021·Biotechnology Advances·Hanna DotterAnn-Christin Eder
Mar 11, 2021·Current Opinion in Chemical Biology·Andrea CasiraghiGiulio Superti-Furga
Mar 28, 2021·Trends in Pharmacological Sciences·Hayden Peacock, Hiroaki Suga
Sep 24, 2018·Gastroenterology·Jianming HuTakaji Wakita
Jun 3, 2021·Pharmaceuticals·Georgia-Myrto PriftiGrigoris Zoidis
Aug 30, 2018·Journal of the American Chemical Society·Toby PassiouraHiroaki Suga
Nov 23, 2019·Journal of the American Chemical Society·Yizhen YinHiroaki Suga
Feb 21, 2019·ACS Medicinal Chemistry Letters·Christoph NitscheGottfried Otting
Aug 28, 2021·Frontiers in Pharmacology·Vojtech DvorakGiulio Superti-Furga
Nov 6, 2018·Chemical Reviews·Yichao HuangHiroaki Suga
Mar 24, 2020·RSC Chemical Biology·Manuel E Otero-RamirezHiroaki Suga

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