Antibiotic drug discovery
Anti-microbial resistance (AMR) is an emerging threat to human health, and one of the greatest challenges facing the world currently.
According to the WHO: “A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century”.
Unfortunately, the problem is not improving, and no new antibiotic class has been developed in decades. The historical low cost and relatively short life-span of antibiotics have resulted in many companies moving away from antibiotic research due to poor economic return relative to investment.
Traditionally, natural products have been the feedstock of new and diverse antibiotics (e.g. penicillins). However, the success of antibiotics is dependent upon their availability. Typically isolated in minute quantities from nature, the foundation of a sustainable supply is vital. This challenge is further compounded by the fact that many natural antibiotics are incredibly complex and sophisticated molecules, rendering them impractical for large scale synthesis (see Chem Eur J 2016).
Rather than pinning all hopes on discovering new antibiotics; a process that is likely to take decades before they reach the clinic, a realistic short-to-medium-term solution is to re-engineer existing, readily available drugs such that they are not susceptible to existing resistance mechanisms. This approach will facilitate a “shortcut to the clinic” by fast-tracking toxicological and clinical trials given prior knowledge of the particular antibiotic class.
In the Moses group, we are developing a novel approach to help fight anti-microbial resistance by employing click chemistry as a tool to reengineer antibiotics to overcome currently known resistance mechanisms.