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Screening and evaluation of potential inhibitors against vaccinia virus from 767 approved drugs
Author(s) -
Wu Jiajing,
Liu Qiang,
Xie Hui,
Chen Ruifeng,
Huang Weijin,
Liang Chunnan,
Xiao Xinyue,
Yu Yongxin,
Wang Youchun
Publication year - 2019
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.25544
Subject(s) - vaccinia , virology , smallpox virus , virus , smallpox , medicine , luciferase , repurposing , smallpox vaccine , pharmacology , chemistry , recombinant dna , biology , cell culture , vaccination , transfection , biochemistry , genetics , gene , ecology
The development of therapies for human smallpox is needed due to the increasing concern over the potential use of smallpox virus as a biological weapon. Here, we report a high‐throughput screening for anti‐smallpox virus drugs from a 767‐small‐molecule library, employing two vaccinia virus (VACV) strains containing firefly luciferase (VTT‐Fluc and VG9‐Fluc) as surrogate viruses. Using an eight‐point dose response format assay, 26 compounds of different pharmacological classes were identified with in vitro anti‐VACV activities. Mycophenolate mofetil (MMF) and tranilast (TRA) were detected to possess the highest anti‐VACV potency (selectivity index values of >334 and >74, respectively); they could inhibit VTT‐Fluc replication in nude mice at 5 days post‐infection by 99% (10 mg/kg, P < .01) and 59% (45 mg/kg, P = .01), respectively, as indicated by bioluminescent intensity. In conclusion, MMF and TRA are promising anti‐smallpox virus candidates for further optimization and repurposing for use in clinical practice.