Authors: Sidharth Chopra, CSIR-Central Drug Research Institute, India
Take a look behind the scenes of a recent Future Microbiology review, entitled ‘An update on drug repurposing: Is it useful for tacking antimicrobial resistance?’ as we ask the authors about what challenges and limitations drug repurposing faces, in addition to why this strategy could be a promising alternative to the traditional drug discovery pipeline.
What inspired you to write this piece?
The impending epidemic spread of antimicrobial resistance (AMR) and concomitant exit of big pharmaceutical industry has severely impacted healthcare systems globally, leading to several national and international efforts dedicated to discovery and development of drugs targeting highly drug-resistant bacterial pathogens. In this context, given the expensive, torturous and winding route to conventional drug discovery, drug-repurposing offers a less expensive, nimbler yet an important side route to identify antimicrobial activity especially in approved non-antibiotics.
Why is drug repurposing favorable in the face of antimicrobial resistance?
Drug-repurposing, especially determining antimicrobial activity in approved non-antibiotics, is one of the most promising strategy since it is highly probable that bacteria because of their previous non-exposure to these scaffolds, might find it more challenging to develop resistance to them, thus increasing the shelf life. Additionally, non-antibiotics might target unconventional targets in inhibiting bacterial growth, thus also leading to identification and validation of novel antibacterial targets.
Have any drugs been successfully repurposed as an antimicrobial?
Yes, drugs have been successfully repurposed as an antimicrobial including moxifloxacin for treatment of tuberculosis. Additionally, several drugs including disulfiram (broad-spectrum antibacterial), auranofin (S. aureus and M. tuberculosis), ebelsen (S. aureus) etc. have shown potential in animal models of bacterial pathogens and are currently in various stages of development.
What are the challenges and limitations of repurposing drugs for antimicrobial activity?
There are several challenges as well as limitations with drug repurposing including lack of pharmacokinetic and pharmacodynamic data at concentrations relevant to antimicrobials as well as several IP issues. However, compared with conventional drug discovery, these challenges and limitations are easily surmountable/achievable.
In your opinion, how useful is drug repurposing for tackling AMR?
Combined with advantages mentioned in answer two, drug-repurposing provides a viable complementary alternative in augmenting the drug discovery pipeline.
What are your predictions for next 10–15 years in this field? What do you hope to see?
I hope to see several non-antibiotics being utilized clinically for the treatment of drug-resistant pathogens as well as identification of non-classical scaffolds offering alternatives augmenting the drug pipeline targeting drug-resistant pathogens. Given the extensive discussions on various viable economic measures to encourage drug discovery by big pharma, drug-repurposing provides a viable, less expensive, nimbler and complementary alternative to augment the drug discovery pipeline.
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