Samolej, J., Correa Mendonca, D. , Upfold, N. , McElwee, M., Landsberger, M., Yakimovich, A., Patel, A. H. , Strang, B. L. and Mercer, J. (2024) Bisbenzimide compounds inhibit the replication of prototype and pandemic potential poxviruses. Microbiology Spectrum, (doi: 10.1128/spectrum.04072-23) (PMID:38376353) (Early Online Publication)
![[img]](https://eprints.gla.ac.uk/style/images/fileicons/text.png) |
Text
318021.pdf - Published Version Available under License Creative Commons Attribution. 2MB |
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: | Articles |
|---|---|
| Additional Information: | B.L.S. was supported by St George’s, University of London. J.M. was supported by the Medical Research Council (MC_PC_19029) and the BBSRC-funded mpox rapid response grant BB/X011607/1. [...] Funding for this research was supported by the BBSRC-funded mpox rapid response grant BB/X011607/1, LifeArc COVID-19 award, and the MRC core award MC_UU_00034/9 (A.H.P.). This work was partially funded by the Center for Advanced Systems Understanding (CASUS), which is financed by Germany’s Federal Ministry of Education and Research (BMBF) and by the Saxon Ministry for Science, Culture, and Tourism (SMWK) with tax funds on the basis of the budget approved by the Saxon State Parliament (A.Y.). |
| Status: | Early Online Publication |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Correa Mendonca, Dr Diogo and Upfold, Dr Nicole and McElwee, Dr Marion and Patel, Professor Arvind |
| Creator Roles: | Correa Mendonca, D.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing – review and editing Upfold, N.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing – review and editing McElwee, M.Investigation Patel, A.Funding acquisition, Supervision, Writing – review and editing |
| Authors: | Samolej, J., Correa Mendonca, D., Upfold, N., McElwee, M., Landsberger, M., Yakimovich, A., Patel, A. H., Strang, B. L., and Mercer, J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Microbiology Spectrum |
| Publisher: | American Society for Microbiology |
| ISSN: | 2165-0497 |
| ISSN (Online): | 2165-0497 |
| Published Online: | 20 February 2024 |
| Copyright Holders: | Copyright: © 2024 Samolej et al. |
| First Published: | First published in Microbiology Spectrum 2024 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information