Escape Mutations in NS4B Render Dengue Virus Insensitive to the Antiviral Activity of the Paracetamol Metabolite AM404 | Zendy

Koen W. R. van Cleef | Zendy; Gijs J. Overheul | Zendy; Michael Thomassen | Zendy; Jenni M. Marjakangas | Zendy; Ronald P. van Rij | Zendy

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Escape Mutations in NS4B Render Dengue Virus Insensitive to the Antiviral Activity of the Paracetamol Metabolite AM404

Author(s) -

Koen W. R. van Cleef,

Gijs J. Overheul,

Michael Thomassen,

Jenni M. Marjakangas,

Ronald P. van Rij

Publication year - 2016

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.02462-15

Subject(s) - dengue virus , dengue fever , virology , virus , metabolite , antibody dependent enhancement , viral replication , antiviral drug , acetaminophen , flavivirus , biology , pharmacology , biochemistry

Despite the enormous disease burden associated with dengue virus infections, a licensed antiviral drug is lacking. Here, we show that the paracetamol (acetaminophen) metabolite AM404 inhibits dengue virus replication. Moreover, we find that mutations in NS4B that were previously found to confer resistance to the antiviral compounds NITD-618 and SDM25N also render dengue virus insensitive to AM404. Our work provides further support for NS4B as a direct or indirect target for antiviral drug development.

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