bioRxiv Microbiology
bioRxiv Microbiology
Preprint
3 years ago

Towards a broad-spectrum antiviral, the myristoyltransferase inhibitor IMP-1088 suppresses viral replication - the Yellow fever NS5 is myristoylated

Jochen Bodem, Melissa Immerheiser, Melissa Zimniak, Helen Hilpert, Nina Geiger, Eva-Maria König
Although a potent Yellow fever vaccine is available since 1937, up to 200.000 severe cases are reported per year, which indicates that virus vaccines require additional support by antiviral therapies. Direct-acting antiviral drugs against severe and widespread diseases, such as DENV and Yellow fever infections with more than millions of diagnosed diseases per year, are still not available. Since antivirals' development against neglected diseases is uneconomical, a broadspectrum antiviral compound would be of public benefit. Here, we show that IMP-1088, a recently published myristoyltransferase-1/2 inhibitor suppressing Rhino- and Polioviruses, inhibits replication of HIV-1, Yellow fever virus, Dengue virus, Vaccinia virus, CMV, and human Herpesvirus 8 in the low nanomolar range, indicating that IMP-1088 has broad-range activity against different pathogenic virus families. The inhibition relies on virally encoded myristoylation signals since Zika, Chikungunya, and Enterovirus 71 are not affected by IMP-1088. Furthermore, we show that the Yellow fever NS5 protein is myristoylated and IMP-1088 treatment of Dengue and Yellow fever infected cells leads to a re-localisation of the viral NS5 proteins.

Publisher URL: http://biorxiv.org/cgi/content/short/2021.03.09.434547v1

DOI: 10.1101/2021.03.09.434547

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