Abstract

IN SILICO ANALYSIS AND NETWORK PHARMACOLOGY OF THE IMPACT OF GENES ASSOCIATED WITH MULTIDRUG-RESISTANT TUBERCULOSIS (MDR-TB)

Krishna Kumar Das, Sunil Kumar Jha, Gurudutta Pattanaik, Yangya Prasad Nath Sharma and Santosh Kumar Behera*

Abstract

Drug-resistant tuberculosis (DR-TB) continues to be a public health crisis worldwide during 2018. It estimates approximately 5,58,000 cases (range, 4,83,000–6,39,000) developed TB resistant to rifampicin (RR-TB). The most effective first line drug, and of these, 82% had multidrug-resistant TB (MDR-TB). Three countries accounted for almost half of the world’s cases of MDR/RR-TB: India (24%), China (13%) and the Russian Federation (10%). Ample of studies were performed in India, based on the previously informed mutations, in addition to which several novel mutations were also observed in the genes such as rpoB (rifampicin), katG, the ribosomal binding site of inhA (isoniazid), gyrA and gyrB (ofloxacin), rpsL and rrs (streptomycin). The current investigation was carried out to explore the gene-gene interaction which are supposed to be the master regulators in MDR-TB. A total of 12 genes were mined from 618 publications in MalaCard which are responsible for MDR-TB. STRING network database reported the genes namely IL10, SLC11A1, TNF, DEFA3, DEFA1 at the core region of the network which are supposed to play a key role in TB. These genes may be also responsible for differentially expressed in MDR-TB disease. The Drug association analysis of Web Gestalt has reported 15 drugs interacted with 12 genes. In the current investigation we would like to suggest for further in vivo and in silico analysis of the reported genes for therapeutics of MDR-TB.

Keywords: MDR-TB; Isoniazid; Rifampicin; Mycobacterium Tuberculosis; STRING.