CMCdG, a Novel Nucleoside Analog with Favorable Safety Features, Exerts Potent Activity against Wild-Type and Entecavir-Resistant Hepatitis B Virus | Zendy

Nobuyo HigashiKuwata | Zendy; Sanae Hayashi | Zendy; Debananda Das | Zendy; Satoru Kohgo | Zendy; Shuko Murakami | Zendy; Shin-ichiro Hattori | Zendy; Shuhei Imoto | Zendy; David Venzon | Zendy; Kamalendra Singh | Zendy; Stefan G. Sarafianos | Zendy; Yasuhito Tanaka | Zendy; Hiroaki Mitsuya | Zendy

Open Access

CMCdG, a Novel Nucleoside Analog with Favorable Safety Features, Exerts Potent Activity against Wild-Type and Entecavir-Resistant Hepatitis B Virus

Author(s) -

Nobuyo HigashiKuwata,

Sanae Hayashi,

Debananda Das,

Satoru Kohgo,

Shuko Murakami,

Shin-ichiro Hattori,

Shuhei Imoto,

David Venzon,

Kamalendra Singh,

Stefan G. Sarafianos,

Yasuhito Tanaka,

Hiroaki Mitsuya

Publication year - 2019

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.02143-18

Subject(s) - entecavir , hepatitis b virus , hbeag , in vivo , viremia , cytotoxicity , microbiology and biotechnology , nucleoside , virology , nucleoside analogue , biology , ic50 , hbsag , chemistry , in vitro , virus , biochemistry , lamivudine

We designed, synthesized, and characterized a novel nucleoside analog, (1S ,3S ,5S )-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-5-hydroxy-1-(hydroxymethyl)-2-methylene-cyclopentanecarbonitrile, or 4′-cyano-methylenecarbocyclic-2′-deoxyguanosine (CMCdG), and evaluated its anti-hepatitis B virus (anti-HBV) activity, safety, and related features. CMCdG’sin vitro activity was determined using quantitative PCR and Southern blotting assays, and its cytotoxicity was determined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, while itsin vivo activity and safety were determined in human liver-chimeric mice infected with wild-type HBV genotype Ce (HBVWT Ce ) and an entecavir (ETV)-resistant HBV variant containing the amino acid substitutions L180M, S202G, and M204V (HBVETV-R L180M/S202G/M204V ).

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