期刊
ANTIVIRAL RESEARCH
卷 183, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.antiviral.2020.104947
关键词
Bunyavirales; Cap-snatching endonuclease; Broad-spectrum antiviral; Metal chelators; Diketo acid; L-742,001
资金
- Bundesministerium far Bildung and Forschung (BMBF) [01 DN17037]
- Progetti di ricerca di Rilevante Interesse Nazionale (PRIN) [2017BMK8JR]
- 'Departments of Excellence' program of the Italian Ministry for Education, University and Research (MIUR, 2018-2022)
- KU Leuven internal project
Several fatal bunyavirus infections lack specific treatment. Here, we show that diketo acids engage a panel of bunyavirus cap-snatching endonucleases, inhibit their catalytic activity and reduce viral replication of a taxonomic representative in vitro. Specifically, the non-salt form of L-742,001 and its derivatives exhibited EC50 values between 5.6 and 6.9 mu M against a recombinant BUNV-mCherry virus. Structural analysis and molecular docking simulations identified traits of both the class of chemical entities and the viral target that could help the design of novel, more potent molecules for the development of pan-bunyavirus antivirals.
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