University of Oulu

Mattila, S., Merilahti, P., Wazir, S., Quirin, T., Maksimainen, M. M., Zhang, Y., Xhaard, H., Lehtiö, L., & Ahola, T. (2021). Macrodomain Binding Compound MRS 2578 Inhibits Alphavirus Replication. Antimicrobial Agents and Chemotherapy, 65(12), e01398-21, https://doi.org/10.1128/aac.01398-21

Macrodomain binding compound MRS 2578 inhibits alphavirus replication

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Author: Mattila, Sari1; Merilahti, Pirjo1; Wazir, Sarah2;
Organizations: 1Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinkigrid.7737.4, Helsinki, Finland
2Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
3Biocenter Oulu, University of Oulu, Oulu, Finland
4Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinkigrid.7737.4, Helsinki, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.7 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021122162296
Language: English
Published: American Society for Microbiology, 2021
Publish Date: 2022-05-17
Description:

Abstract

Alphaviruses are positive-strand RNA viruses causing febrile disease. Macrodomain-containing proteins, involved in ADP-ribose-mediated signaling, are encoded by both host cells and several virus groups, including alphaviruses. In this study, compound MRS 2578 that targets the human ADP-ribose glycohydrolase MacroD1 inhibited Semliki Forest virus production as well as viral RNA replication and replicase protein expression. The inhibitor was similarly active in alphavirus trans-replication systems, indicating that it targets the viral RNA replication stage.

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Series: Antimicrobial agents and chemotherapy
ISSN: 0066-4804
ISSN-E: 1098-6596
ISSN-L: 0066-4804
Volume: 65
Issue: 12
Article number: e01398-21
DOI: 10.1128/AAC.01398-21
OADOI: https://oadoi.org/10.1128/AAC.01398-21
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Subjects:
Funding: This work was supported by the Academy of Finland (grants 307802 (TA), 287063 (LL) and 294085 (LL)), and the Sigrid Jusélius Foundation (LL). The funders had no role in study design, data collection and interpretation,or the decision to submit the work for publication.
Copyright information: © American Society for Microbiology.