Inhibition of Mycobacterium tuberculosis tRNA-Ligases Using siRNA-Based Gene Silencing Method: A Computational Approach

J Comput Biol. 2020 Jan;27(1):91-99. doi: 10.1089/cmb.2019.0156. Epub 2019 Aug 22.

Abstract

Tuberculosis (TB) is a major public health problem in several countries. Development of first-line and second-line drug resistance strains of Mycobacterium tuberculosis further complicated the management of the disease. Despite available drugs to treat TB, 1.6 million people died from the disease in 2017. In this study, we designed 10 siRNAs against 8 tRNA ligases of M. tuberculosis and validated their usefulness for inhibition of protein synthesis by using computational approach. We found that the predicted siRNAs efficiently form seed duplex complex against their respective mRNA targets. Other different computational approaches were also undertaken to assess the stability, accessibility, and strength of seed duplex complex of designed siRNA and targeted mRNA. On the basis of the computational approach, we reciprocated that the technique will help in opening a new window in the field of TB control program and could be taken for further clinical studies to find their appropriateness for TB eradication.

Keywords: Mycobacterium tuberculosis; aminoacyl–tRNA synthetase; gene silencing; siRNA; tRNA ligases; tuberculosis.

MeSH terms

  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / genetics
  • Computational Biology / methods*
  • Drug Resistance, Bacterial / drug effects
  • Gene Expression Regulation, Bacterial / drug effects
  • Humans
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology*
  • Nucleic Acid Conformation
  • RNA Ligase (ATP) / antagonists & inhibitors
  • RNA Ligase (ATP) / genetics*
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology*
  • Tuberculosis / drug therapy
  • Tuberculosis / prevention & control

Substances

  • Bacterial Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA Ligase (ATP)