CSIR scientists find novel approach to drug discovery
Q. In a novel approach to TB drug discovery, CSIR scientists have done which of the following?- Published on 02 May 17a. Speeded up drug discovery by finding potential non toxic drug targets
b. Reduced the cost of drug discovery by lowering chances of failure
c. Both a and b
d. Neither a nor b
ANSWER: Both a and b
In a completely different approach to drug discovery, Delhi’s CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) has used a combination of approaches to predict potential drug targets in Mycobacterium tuberculosis.
This is a TB-causing bacteria.
The novel method not only helps in speeding up drug discovery by finding potential, non-toxic drug targets but will also cost far less by reducing the chances of failure.
The results were published in the journal Scientific Reports.
Conventionally, drug discovery was never looked at from a systems biology point of view.
The approach the scientists used was rather unconventional, aimed at finding targets first based on evolutionary conservation principle in an organism,
Based on a previous study that used the Systems Biology Spindle Map (SBSM) approach, the team was able to identify 890 novel, non-toxic gene drug targets.
Using computational approaches, the potential drug targets were reduced to 116 essential genes; these 116 genes are so vital that any inhibition would kill the bacteria.
In order to identify drug targets with the least likelihood of side effects, the 116 essential genes were compared with the human genome and human microbiome at the sequence level to identify genes that did not have any similarity (homology) with human genome sequences.
Of the 116 genes, 104 were found to have no similarity with the human genome sequences, meaning any drug developed targeting these 104 genes will only target the TB bacteria and not cause any harm to human cells.
The potential drug targets were further shortlisted to 33 genes.
The presence or absence of mutations in any of the 33 genes was evaluated using the Genome-wide Mycobacterium tuberculosis Variation (GMTV) database.
The genes which are essential for bacteria never undergo any mutations as that would be lethal for their survival.
The crystal structure, which is essential for carrying out drug discovery process, was available for 15 of the 33 targets.
Once scientists have the targets and have structures of these targets then can tailor-make molecules to inhibit even MDR-TB and XDR-TB,.
The team has already carried out druggability assessment (to find out if the targets have certain properties for a drug to bind to receptors) for all the 33 gene targets.
Most of the 33 genes were found to be highly druggable validating the study.
There is a need for drug discovery to move from Wright brothers’ era of trial and error method. The trial and error approach is slow and too expensive.
All the genes, targets and even ligands will be in open source so anyone can develop new drug molecules.
