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Bisbenzimide compounds inhibit replication of prototype and pandemic potential poxviruses

Samolej, J; Correa Mendonca, D; Upfold, N; McElwee, M; Landsberger, M; Yakimovich, A; Patel, AH; Strang, BL; Mercer, J (2024) Bisbenzimide compounds inhibit replication of prototype and pandemic potential poxviruses. Microbiology spectrum, 12 (4). e04072-23. ISSN 2165-0497 https://doi.org/10.1128/spectrum.04072-23
SGUL Authors: Strang, Blair Lewis

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Abstract

We previously identified the bisbenzimide Hoechst 33342 (H42) as a potent multi-stage inhibitor of the prototypic poxvirus, the vaccinia virus (VACV), and several parapoxviruses. A recent report showed that novel bisbenzimide compounds similar in structure to H42 could prevent human cytomegalovirus replication. Here, we assessed whether these compounds could also serve as poxvirus inhibitors. Using virological assays, we show that these bisbenzimide compounds inhibit VACV spread, plaque formation, and the production of infectious progeny VACV with relatively low cell toxicity. Further analysis of the VACV lifecycle indicated that the effective bisbenzimide compounds had little impact on VACV early gene expression but inhibited VACV late gene expression and truncated the formation of VACV replication sites. Additionally, we found that bisbenzimide compounds, including H42, can inhibit both monkeypox and a VACV mutant resistant to the widely used anti-poxvirus drug TPOXX (Tecovirimat). Therefore, the tested bisbenzimide compounds were inhibitors of both prototypic and pandemic potential poxviruses and could be developed for use in situations where anti-poxvirus drug resistance may occur. Additionally, these data suggest that bisbenzimide compounds may serve as broad-activity antiviral compounds, targeting diverse DNA viruses such as poxviruses and betaherpesviruses.

Item Type: Article
Additional Information: Copyright © 2024 Samolej et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Microbiology spectrum
ISSN: 2165-0497
Dates:
DateEvent
2 April 2024Published
20 February 2024Published Online
1 February 2024Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
MC_PC_19029Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
BB/X011607/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
MC_UU_00034/9Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
URI: https://openaccess.sgul.ac.uk/id/eprint/116250
Publisher's version: https://doi.org/10.1128/spectrum.04072-23

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