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Diketo acids inhibit the cap-snatching endonuclease of several Bunyavirales

Fernández-García, Yaiza, Horst, Sebastiaan ter, Bassetto, Marcella ORCID:, Brancale, Andrea ORCID:, Neyts, Johan, Rogolino, Dominga, Sechi, Mario, Carcelli, Mauro, Günther, Stephan and Rocha-Pereira, Joana 2020. Diketo acids inhibit the cap-snatching endonuclease of several Bunyavirales. Antiviral Research 183 , 104947. 10.1016/j.antiviral.2020.104947

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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 to 6.9 μM 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Publisher: Elsevier Masson
ISSN: 0166-3542
Date of First Compliant Deposit: 1 October 2020
Date of Acceptance: 29 August 2020
Last Modified: 29 May 2024 00:35

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