In order for viruses to proliferate, they usually need to be supported by infected cells. In many cases, the molecules they need to replicate their own genetic material are only found in the nucleus of the host cell before infecting other cells in the vicinity. But not all viruses enter the nucleus. Some viruses stay in the cytoplasm and must therefore be able to replicate their genetic material independently. To do so, they must bring their own "machined parts". A key player in this process is a specialized enzyme, RNA polymerase, composed of various subunits. This enzyme reads genetic information from the viral genome and transcribes it into messenger RNA (mRNA) and uses mRNA as a blueprint for proteins encoded in the genome.
About one in three human proteins is understudied. Even when quantifying data is available from multiple sources, "dark" genes and proteins are simply not well characterized (Figure 1).
Are you curious where dark gene hunting leads? There are a number of resources:
Things like gene editing, stem cells, immunotherapies and new types of biologics are now mega-trends in the pharmaceutical industry, widely covered in media, and I guess there is little doubt that biology is the next big thing in medicine. However, in this post I would like to outline several hot areas in small molecule drug discovery, suggesting a lot of untapped potential and investment prospects in this more “traditional” pharmaceutical research space.
Immunotherapies are hot property. Immuno-oncology is the crown jewel. But the road to riches, and more importantly cancer cures, is now crowded and full of potholes. Drug hunters need to look ahead, beyond the discovery process itself, to the reality of the many impediments that will confront drug candidates as they proceed towards the clinic in today's landscape. Here, I present three insights from current events, the third one taking a contrarian position.
The question is often raised, but the answer remains to be uncovered because the definition of drug "target" continues to evolve. Historical conceptualization is focused on catalytic sites, substrate binding sites, or epigenetic modification sites. Current understanding that protein-protein interactions are druggable, along with the emerging realization that "nodes" in signaling pathways and biological networks themselves can be manipulated with small molecules in non-traditional ways, has opened up new targeting options. This review is intended to provide a status update, and you can also access a list of 36 actionable web resources for target hunting.