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A Small-Molecule Oligosaccharyltransferase Inhibitor With Pan-flaviviral Activity

A Small-Molecule Oligosaccharyltransferase Inhibitor With Pan-flaviviral Activity

Andreas S Puschnik, Caleb D Marceau, Yaw Shin Ooi, Karim Majzoub, Natalie Rinis, Joseph N Contessa, Jan E Carette

Cell Rep. 2017 Dec 12;21(11):3032-3039.

PMID: 29241533

Abstract:

The mosquito-borne flaviviruses include important human pathogens such as dengue, Zika, West Nile, and yellow fever viruses, which pose a serious threat for global health. Recent genetic screens identified endoplasmic reticulum (ER)-membrane multiprotein complexes, including the oligosaccharyltransferase (OST) complex, as critical flavivirus host factors. Here, we show that a chemical modulator of the OST complex termed NGI-1 has promising antiviral activity against flavivirus infections. We demonstrate that NGI-1 blocks viral RNA replication and that antiviral activity does not depend on inhibition of the N-glycosylation function of the OST. Viral mutants adapted to replicate in cells deficient of the OST complex showed resistance to NGI-1 treatment, reinforcing the on-target activity of NGI-1. Lastly, we show that NGI-1 also has strong antiviral activity in primary and disease-relevant cell types. This study provides an example for advancing from the identification of genetic determinants of infection to a host-directed antiviral compound with broad activity against flaviviruses.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP790702577	NGI-1		790702-57-7	Price

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