Diketo acids inhibit the cap-snatching endonuclease of several Bunyavirales

Yaiza, Fernández-García; Horst, Sebastiaan ter; Bassetto, Marcella; Brancale, Andrea; Neyts, Johan; Rogolino, Dominga; Sechi, Mario; Carcelli, Mauro; Günther, Stephan; Rocha‐Pereira, Joana

doi:10.1016/j.antiviral.2020.104947

Cited by 29 publications

(13 citation statements)

References 23 publications

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“…The previously described thermal shift assay is also applicable for PA endonuclease characterization as reported by Omoto et al., [138] Wang et al., [140] and Fernandez‐Garcia et al. [142] They characterized the enzymes from influenza A and B viruses, SFTSV and HRTV, and several Bunyavirales , respectively.…”

Section: Cap Snatching Endonuclease Assaysmentioning

confidence: 99%

“… [137] Fernandez‐Garcia et al. [142] exploited further structures of diketo acids to develop potent PA endonuclease inhibitors of selected Bunyavirales , such as La Crosse virus , Rift Valley Fever virus , and Andes virus . Baloxavir acid (Figure 8 Y) and its prodrug, baloxavir marboxil containing additional phenolic hydroxyl groups, have been synthesized as alternatives for influenza treatment.…”

Section: Capping Inhibitionmentioning

confidence: 99%

“…Baughman et al proposed a fluorescent probe based on the structure of an L-742,001 inhibitor (4-substitued 2,4-dioxobutanoic acid), wherein piperazine nitrogen is substituted by fluorescein. [141] The previously described thermal shift assay is also applicable for PA endonuclease characterization as reported by Omoto et al, [138] Wang et al, [140] and Fernandez-Garcia et al [142] They characterized the enzymes from influenza A and B viruses, SFTSV and HRTV, and several Bunyavirales, respectively.…”

Section: Cap Snatching Endonuclease Assaysmentioning

confidence: 99%

“…For example, 2-hydroxy-4-oxo-4-phenyl-2-butenoic acid (Figure 8X), [146] a known inhibitor of the cap-snatching reaction, was used to validate the pull-down assay that combines radioactive labeling with specific biotin-streptavidin interactions. [137] Fernandez-Garcia et al [142] exploited further structures of diketo acids to develop potent PA endonuclease inhibitors of selected Bunyavirales, such as La Crosse virus, Rift Valley Fever virus, and Andes virus. Baloxavir acid (Figure 8Y) and its prodrug, baloxavir marboxil containing additional phenolic hydroxyl groups, have been synthesized as alternatives for influenza treatment.…”

Section: Capping Inhibitionmentioning

confidence: 99%

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Enzymatic Assays to Explore Viral mRNA Capping Machinery

Kasprzyk

Jemielity

2021

ChemBioChem

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In eukaryotes, mRNA is modified by the addition of the 7‐methylguanosine (m 7 G) 5′ cap to protect mRNA from premature degradation, thereby enhancing translation and enabling differentiation between self (endogenous) and non‐self RNAs (e. g., viral ones). Viruses often develop their own mRNA capping pathways to augment the expression of their proteins and escape host innate immune response. Insights into this capping system may provide new ideas for therapeutic interventions and facilitate drug discovery, e. g., against viruses that cause pandemic outbreaks, such as beta‐coronaviruses SARS‐CoV (2002), MARS‐CoV (2012), and the most recent SARS‐CoV‐2. Thus, proper methods for the screening of large compound libraries are required to identify lead structures that could serve as a basis for rational antiviral drug design. This review summarizes the methods that allow the monitoring of the activity and inhibition of enzymes involved in mRNA capping.

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Section: Cap Snatching Endonuclease Assaysmentioning

confidence: 99%

Section: Capping Inhibitionmentioning

confidence: 99%

Section: Cap Snatching Endonuclease Assaysmentioning

confidence: 99%

Section: Capping Inhibitionmentioning

confidence: 99%

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Enzymatic Assays to Explore Viral mRNA Capping Machinery

Kasprzyk

Jemielity

2021

ChemBioChem

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“…Results that we obtained using this assay have contributed to published works on the anti-BUNV activity of baloxavir and other diketo acid-related endonuclease inhibitors. 4,5 1. BUNV-mCherry elite stock 3 4.…”

Section: Introductionmentioning

confidence: 99%

Screening and in vitro antiviral assessment of small molecules against fluorescent protein-expressing Bunyamwera virus in a cell-based assay using high-content imaging

Horst

Chiu

Neyts

et al. 2021

Antivir Chem Chemother

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Many species of the order Bunyavirales contain potentially fatal viruses that lack effective medical countermeasures and are therefore collectively a major public health threat. Here, we describe a cell-based assay using Bunyamwera virus (BUNV)-mCherry to identify and characterize new antiviral molecules against bunyaviruses. BUNV is the type species for the genus Orthobunyavirus and has been reported to cause mild symptoms in humans, such as fever, joint pain, and rash. One major benefit of using our fluorescence-based assay over classical CPE-based assays is the fact that the antiviral effect of the tested compounds and their effect on the cell viability can be determined within the same assay well. For that reason, this type of assay could significantly advance our preclinical efforts towards finding new antiviral molecules against bunyaviruses.

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