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Article

Novel Broad-Spectrum Antiviral Inhibitors Targeting Host Factors Essential for Replication of Pathogenic RNA Viruses

1
Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Stockholm, Sweden
2
National Veterinary Institute, SE-756 51 Uppsala, Sweden
3
Department of Microbiology, Public Health Agency of Sweden, 171 65 Stockholm, Sweden
4
Department of Molecular Medicine, University of Padova, 35121 Padova, Italy
5
Unit of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute and Karolinska University Hospital, 17177 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Academic Editor: Karla Helbig
Viruses 2020, 12(12), 1423; https://doi.org/10.3390/v12121423
Received: 10 November 2020 / Revised: 26 November 2020 / Accepted: 7 December 2020 / Published: 10 December 2020
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
Recent RNA virus outbreaks such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ebola virus (EBOV) have caused worldwide health emergencies highlighting the urgent need for new antiviral strategies. Targeting host cell pathways supporting viral replication is an attractive approach for development of antiviral compounds, especially with new, unexplored viruses where knowledge of virus biology is limited. Here, we present a strategy to identify host-targeted small molecule inhibitors using an image-based phenotypic antiviral screening assay followed by extensive target identification efforts revealing altered cellular pathways upon antiviral compound treatment. The newly discovered antiviral compounds showed broad-range antiviral activity against pathogenic RNA viruses such as SARS-CoV-2, EBOV and Crimean-Congo hemorrhagic fever virus (CCHFV). Target identification of the antiviral compounds by thermal protein profiling revealed major effects on proteostasis pathways and disturbance in interactions between cellular HSP70 complex and viral proteins, illustrating the supportive role of HSP70 on many RNA viruses across virus families. Collectively, this strategy identifies new small molecule inhibitors with broad antiviral activity against pathogenic RNA viruses, but also uncovers novel virus biology urgently needed for design of new antiviral therapies. View Full-Text
Keywords: antivirals; virus-host interactions; pathogenic RNA viruses; HSP70; target identification antivirals; virus-host interactions; pathogenic RNA viruses; HSP70; target identification
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MDPI and ACS Style

Tampere, M.; Pettke, A.; Salata, C.; Wallner, O.; Koolmeister, T.; Cazares-Körner, A.; Visnes, T.; Hesselman, M.C.; Kunold, E.; Wiita, E.; Kalderén, C.; Lightowler, M.; Jemth, A.-S.; Lehtiö, J.; Rosenquist, Å.; Warpman-Berglund, U.; Helleday, T.; Mirazimi, A.; Jafari, R.; Puumalainen, M.-R. Novel Broad-Spectrum Antiviral Inhibitors Targeting Host Factors Essential for Replication of Pathogenic RNA Viruses. Viruses 2020, 12, 1423. https://doi.org/10.3390/v12121423

AMA Style

Tampere M, Pettke A, Salata C, Wallner O, Koolmeister T, Cazares-Körner A, Visnes T, Hesselman MC, Kunold E, Wiita E, Kalderén C, Lightowler M, Jemth A-S, Lehtiö J, Rosenquist Å, Warpman-Berglund U, Helleday T, Mirazimi A, Jafari R, Puumalainen M-R. Novel Broad-Spectrum Antiviral Inhibitors Targeting Host Factors Essential for Replication of Pathogenic RNA Viruses. Viruses. 2020; 12(12):1423. https://doi.org/10.3390/v12121423

Chicago/Turabian Style

Tampere, Marianna, Aleksandra Pettke, Cristiano Salata, Olov Wallner, Tobias Koolmeister, Armando Cazares-Körner, Torkild Visnes, Maria C. Hesselman, Elena Kunold, Elisee Wiita, Christina Kalderén, Molly Lightowler, Ann-Sofie Jemth, Janne Lehtiö, Åsa Rosenquist, Ulrika Warpman-Berglund, Thomas Helleday, Ali Mirazimi, Rozbeh Jafari, and Marjo-Riitta Puumalainen. 2020. "Novel Broad-Spectrum Antiviral Inhibitors Targeting Host Factors Essential for Replication of Pathogenic RNA Viruses" Viruses 12, no. 12: 1423. https://doi.org/10.3390/v12121423

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