Discovering mycobacterial lectins as potential drug targets and vaccine candidates for tuberculosis treatment: a theoretical approach

Abstract

M. tuberculosis proliferates within the macrophages during infection and they are bounded by carbohydrates in the cell wall, called lectins. Despite their surface localization, the studies on exact functions of lectins are unexplored. Hence, in our study, using insilico approaches, 11 potential lectins of Mtb was explored as potential drug targets and vaccine candidates. Initially, a gene interaction network was constructed for the 11 potential lectins and identified its functional partners. A gene ontology analysis was also performed for the 11 mycobacterial lectins along with its functional partners and found most of the proteins are present in the extracellular region of the bacterium and belongs to the PE/PPE family of proteins. Further, molecular docking studies were performed for two of the potential lectins (Rv2075c and Rv1917c). A novel series of quinoxalinone and fucoidan derivatives have been made to dock against these selected lectins. Molecular docking study reveals that quinoxalinone derivatives showed better affinity against Rv2075c, whereas fucoidan derivatives have good binding affinity against Rv1917c. Moreover, the mycobacterial lectins can interact with the host and they are considered as potential vaccine candidates. Hence, immunoinformatics study was carried out for all the 11 potential lectins. B-cell and T-cell binding epitopes were predicted using insilico tools. Further, an immunodominant epitope 1062 SIPAIPLSVEV 1072 of Rv1917c was identified, which was predicted to bind B-cell and most of the MHC alleles. Thus, the study has explored that mycobacterial lectins could be potentially used as drug targets and vaccine candidates for tuberculosis treatment.

Short Communication: Cloning, production and responses of the sMTL-13 protein (13 kDa lectin secretion) Mycobacterium tuberculosis against Interleukin 6

“…Because lectins are present on the surface of mycobacterial cells, they can be easily recognized by immune cells so that lectins can be used as potential vaccine candidates. Several studies have shown binding epitopes of MHC-I and MHC-II to mycobacterial lectins (Sundar et al 2021). A DNA vaccine from Rv1419 has been successfully developed and can induce a weaker humoral immune response and a stronger cellular immune response in mice.…”