What’s New in (Bio)Pharma?

Putting COVID-19 on a diet
 

It turns out SARS-CoV-2 loves fat. Like, a lot. Based on observations that some people with a higher body-mass index were more sensitive to COVID-19, researchers from Oregon Health & Science University and the Department of Energy’s Pacific Northwest National Laboratory decided to use nontargeted lipidomics to look a little closer at how the virus alters lipid levels in cells. What they saw was a massive shift, with some fats increasing 64-fold. Further research revealed the virus completely takes over the fat-processing system in the body. Based on this discovery, the team decided to put the virus on a diet – pumping it with weight-loss drugs (small-molecule glycerolipid biosynthesis inhibitors) to cut off its fuel supply and stop it replicating. Crucially, the authors found this inhibition works across the main variants of concern, meaning this approach could continue to work as the virus evolves.

Combating hunger
 

Talking of diets, have researchers just discovered the latest, greatest diet pill? Perhaps. Jonathan Long and his team published a study showing that exercise induces the production of Lac-Phe – an “anti-hunger” molecule that appears to suppress appetite post-exercise (at least in mice). Using MS, the team studied how the metabolome shifted and changed during exercise, and eventually honed in on one peak in particular with a mass of 236. Thanks to some collaborative work with a team at Stanford University, they were able to decipher that this molecule was a combination of lactate and phenylalanine. They even went further and fed this molecule to obese mice, finding that their food intake dropped by about 30 percent. The next steps are to elucidate the mechanism behind this activity.

A boon for drug discovery
 

Drug discovery just got a new best friend in the shape native ambient MS. By applying this technique to the analysis of non-covalent protein-drug complexes in vivo, researchers have managed to gather more information about drug-target interactions in their native physiological environment. “Using mass spectrometry on proteins is often compared to making an elephant fly.,” said lead researcher Helen Cooper. “What we’ve done is add an unsecured hat – the drug molecule – to the elephant, and measured the whole process. It’s exciting because it opens up the possibility of being able to follow the route of a drug through the body. By identifying which proteins it interacts with, scientists will be able to predict at an earlier stage whether or not it will have the desired therapeutic effect.” The hope is that this same technique can next be applied to human tissues, and that it will help guide drug discovery efforts in the future.