Biotech Values

[biomaven0]

Well here is my understanding of what they did:

1. They used a cell-based HCV replicon and did a high-throughput screen against the deck of BMS compounds (with some sort of normal cell-based control so they weren't just picking toxic compounds). So right off that's a very expensive and ambitious project, and of course non-pharma companies don't have access to a comparable set of compounds.

2. In the screening, they found a modest potency compound that they then used to produce some HCV cell lines that were resistant to it.

3. They then did some SAR analysis which enabled them to find a much more potent compound to which the above resistant cell lines were also resistant.

4. They then analyzed where the HCV had mutated so as to become resistant to both these compounds, and this analysis together with the structure of the two compounds revealed that NS5A was their mutual target.

That of course came as a surprise to them, as NS5A had no enzymatic activity and an unknown function.

(I might have gotten some of this wrong as I'm going by memory from a very dense article I skimmed a couple of weeks back).

I have no idea if anyone has ever done something similar before (either in HCV or perhaps HIV) - I've always been quite unclear as to where targets come from. Presumably this methodology would only work for a rapidly mutating virus. But seems like a very nice piece of work even if it wasn't totally original.

Peter