Peptide Derived from Bungarus caeruleus Proteome Binds with Higher Affinity to Ethionamide Resistance Regulator of Mycobacterium tuberculosis than Isoniazid

Antimicrobial resistance has become a serious health concern worldwide because of high morbidity and mortality. An increase in multi-drug and extensively drug-resistant (MDR and XDR) strains of Mycobacterium tuberculosis has trigged the finding of effective therapeutic alternatives. A computational approach has been utilized to predict and prediction of novel antimycobacterial peptides using the proteome sequences of Bungarus caeruleus (Indian Krait). In-silico digestion of proteome sequences using five different enzymes yielded more than 1000 shorter peptides sequences. Further, the antibacterial peptide was predicted using DBAASP server. Based on the various physiochemical properties (including stability, half-life and ADMET) 11 peptides were taken for molecular docking study. Ethionamide resistance regulator (EthR)-peptide docking was performed using HADDOCK server, and the peptide sequence HGATVAVKQVNRCSKNHL shows the maximum binding affinity with EthR . The binding score was found to be maximum for the peptide with -9.3 kcal/mol in comparison with the standard drug (Isoniazid) with -5.69 kcal/mol when analysed with PRODIGY server. The complex structure and the interactions were found to be stable during the 100 ns molecular dynamics simulations using Gromacs-2023.1. The stability of the complex was analysed in terms of RMSD, RMSF, radius of gyration, H-bond, and SASA. MMPBSA analysis indicated that the free energy of interaction of EthR with peptide and Isoniazid was found to be -36.15 kcal/mol and -6.95 kcal/mol respectively. The results indicate the potential anti-mycobacterial property of this 18-mer peptide which can be validated further through in-vitro and in-vivo studies.