Inhospitable host

Chugai Pharmaceutical Co. Ltd. thinks that targeting host cell mechanisms that enable hepatitis C virus to replicate may provide an alternative to targeting the virus, which is prone to mutation and resistance. Chugai published in this month's Nature Chemical Biologythe mechanism of action of NA255, an HCV replication inhibitor, and proposed that its target, human serine palmitoyltransferase (SPT) enzyme, is a new drug target for HCV. A compound related to NA255 is in late preclinical development at the company.

Chugai (Tokyo, Japan), a subsidiary of Roche (SWX:ROCZ, Basel, Switzerland), used cell-based high throughput screening of natural product libraries derived from microbial and fungal metabolites to identify NA255. Although the small molecule fungal metabolite was identified as a potent inhibitor of HCV replication, the researchers were surprised to find it did not affect HCV enzymes. Instead, they found it inhibited SPT, which in turn blocked the de novo synthesis of sphingolipids in host cells in culture. ...