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In silico drug repurposing via chemical-protein interaction analysis, a proof-of-concept study: targeting pyocyanin based virulence of antibiotic resistant Pseudomonas aeruginosa

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Research Paper 01/03/2018
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In silico drug repurposing via chemical-protein interaction analysis, a proof-of-concept study: targeting pyocyanin based virulence of antibiotic resistant Pseudomonas aeruginosa

Muhammad Ibrahim Rashid, Parkha Tariq, Habiba Rashid, Amjad Ali, Saadia Andleeb
Int. J. Biosci.12( 3), 87-96, March 2018.
Certificate: IJB 2018 [Generate Certificate]
Key: Anti-virulenceChemical-protein interactionDrug repurposingPseudomonas aeruginosaPyocyanin

Abstract

World Health Organization has classified Pseudomonas aeruginosa as one of top priority threat in terms of the prevailing pandemic scenario of antibiotic-resistant superbugs. This pathogen is widespread in healthcare settings and is listed as one of the top three nosocomial infectious agents. A susceptible population is vulnerable due to lack of vaccine availability to combat this opportunistic pathogen. Pyocyanin (PCN) is considered as a prime virulence factor of P. aeruginosa among many others. A wide range of bioactivities have been attributed to this compound primarily based on is redox active nature. We attempted to exploit structural information of PCN in order to screen available drug pool for disrupting or reducing PCN production. In this proof of concept study, PCN molecule’s structure was studied for a potential drug hit via studying chemical-protein interaction (CPI). The CPI data was used to identify query-drug interactions.  A screening was performed and high probability hits were selected. The predicted targets were tested for inhibition of PCN production. Piperaquine showed remarkable inhibition of PCN biosynthesis. This predicted reported target may provide a basis for the development of a reliable anti-virulence drug against acute and urinary tract infections by P. aeruginosa. The approach adopted here could be extended to other bacterial pathogens for potential immunogenic target predictions and ultimately successful drug development.

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