2026-10-11T07:53:45Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33791547 2026-09-22T13:39:53Z category_1 category_4 category_7 category_19 category_21 category_873 category_931 category_64 category_132 category_134 portal_87 item_type_3 month_year_09_2026

Discovery of the nucleoside analogue FMAU as a broad-spectrum anti-orthopoxvirus inhibitor in vitro and in vivo using a structure-guided hit expansion strategy Tingting Zheng (400620) Yong Feng (828176) Chang Xu (102022) Arnaud Fondjo Kouam (21416999) Shiman Chen (24932121) Farkhod Eshboev (23127825) Yingxia Liu (792213) Fuxiang Wang (8316573) Yang Yang (45629) Jianxun Qi (221120) Lifeng Fu (2866880) Biophysics Biochemistry Medicine Pharmacology Biotechnology Chemical Sciences not elsewhere classified Information Systems not elsewhere classified Cancer Infectious Diseases Virology MPXV FMAU orthopoxvirus nucleoside analogue antiviral agent <p>Mpox remains a critical public health threat worldwide, and currently available therapeutics against orthopoxvirus infections remain very limited. In this study, we identified 2'-deoxy-2'-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU) as a broad-spectrum anti-orthopoxvirus candidate through nucleos(t)ide analogue library screening combined with a structure-guided hit expansion strategy. In Vero cells, FMAU exerted potent in vitro antiviral activity against vaccinia virus (VACV) and monkeypox virus (MPXV), with EC₅₀ values of 1.99 μM and 30 nM, respectively, while exhibiting no apparent cytotoxicity, as reflected by a CC₅₀ value greater than 200 μM. In vivo mouse studies further showed that FMAU treatment provided full protection against lethal VACV and MPXV challenges, while significantly reducing viral loads in lung tissues. Importantly, oral FMAU administration retained potent therapeutic efficacy against MPXV in a mouse model of MPXV infection. Collectively, our findings identify FMAU as a promising oral anti-orthopoxvirus drug candidate and support its further preclinical evaluation.</p> 2026-09-22T13:39:53Z Dataset Dataset 10.6084/m9.figshare.33791547.v2 https://figshare.com/articles/dataset/Discovery_of_the_Nucleoside_Analog_FMAU_as_a_Broad-Spectrum_Anti-Orthopoxvirus_Inhibitor_In_Vitro_and_In_Vivo_Using_a_Structure-guided_Hit_Expansion_Strategy/33791547 CC BY 4.0