New analysis being offered at this yr’s European Congress of Scientific Microbiology & Infectious Illnesses (ECCMID) being held on-line (9-12 July) identifies drugs that could doubtlessly be repurposed for the remedy of gonorrhoea (Neisseria gonorrhoeae [Ng]): a sexually transmitted an infection which is turning into more and more resistant to existing antibiotics.
The decreased susceptibility of the Ng bacterium to prolonged spectrum cephalosporin antibiotics has change into an vital public well being subject as circumstances of this frequent an infection change into harder to treat.
The research by Dr. Liliana Rodrigues and colleagues at International Well being and Tropical Drugs (GHTM), Institute of Hygiene and Tropical Drugs (IHMT), Universidade Nova de Lisboa, Lisbon, Portugal, used pc evaluation of candidate drugs to predict whether or not they would work together with proteins within the Ng bacterium concerned in energy metabolism and the removing of poisonous substances.
One potential methodology for growing the effectiveness of antimicrobial drugs is to goal sure protein-based constructions referred to as efflux pumps that are embedded within the mobile membrane and act to take away poisonous compounds which could injury the perform or construction of that cell. These pumps play an vital position in bacterial survival by eradicating antimicrobial compounds that have entered the cell, thus making therapies for infection much less efficient. Drugs which goal the precise proteins in efflux pumps could be used to deactivate them, and when utilized in mixture with present antimicrobials could enhance or restore the exercise of those drugs by growing their focus inside the bacterial cells.
Growth of any brand-new drug is a protracted and costly course of, and a more cost effective technique is to research existing compounds that are recognized to be protected and have been accepted for clinical use for different ailments, to discover these which act as efflux inhibitors and could doubtlessly be repurposed for this position.
The staff’s evaluation predicted the existence of 100 Ng drug targets which have been related to 680 existing accepted drugs. Additional detailed examination of those outcomes narrowed this down to 30 potential targets and 57 drug candidates. These included dequalinium (an antiseptic), doxorubicin (a most cancers chemotherapy drug), metformin (used for diabetes), and thiabendazole (used to treat worm infections). These already-approved drugs goal a multidrug efflux protein, and the enzymes NADH-dehydrogenase, flavoprotein-ubiquinone oxidoreductase, and succinate dehydrogenase, respectively.
The authors conclude: “The recognized drugs are accepted for a wide range of indications, akin to epilepsy, hypertension, diabetes and most cancers and will function lead compounds for the event of latest drugs in opposition to gonorrhoea. This work could assist set up a brand new paradigm for the design of latest drugs and therapeutic methods to be used within the remedy of gonorrhoea infections.”
European Society of Scientific Microbiology and Infectious Illnesses
Study identifies existing drugs that could be repurposed to treat gonorrhea (2021, July 1)
retrieved 1 July 2021
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