In silico evaluation of snake venom proteins against multidrug-resistant Mycobacterium tuberculosis: A molecular dynamics study and simulation dynamic

Background: Mycobacterium tuberculosis (Mtb), a pathogen that belongs to the M. tuberculosis complex (MTBC), causes tuberculosis (TB), an infectious bacterial disease. Although it usually affects the lungs and results in pulmonary tuberculosis, it can also lead to extrapulmonary tuberculosis by affecting other regions of the body. TB, which ranks first on the list of infectious diseases that kill the most people, affects one-third of the world’s population and has a high mortality and morbidity rate. The clinical treatment of active TB infection mainly relies on the use of isoniazid INH in combination with three other drugs—rifampin, pyrazinamide,, and ethambutol. However, the situation is getting worse due to the rise of extremely drug-resistant tuberculosis (XDR-TB) and multidrug-resistant tuberculosis (MDR-TB). Finding more effective drugs is always a top priority. In this regard, animal venoms, such as snake toxins, contain antibacterial chemicals that have significant therapeutic properties and prevent bacterial infections and disease progression. This suggests that snake venom venom is a good natural source of promising novel anti-TB drugs.
Aim: This study examines the snake venom protein’s capacity in silico to interrupt the intracellular enzymes of M. tuberculosis, which is responsible for the development of MDR-TB in humans.
Methods: The active protein structure of catalase-peroxidase, RNA polymerase, and snake venom proteins was derived from the protein RCSB-PDB. The interactions between those proteins and the targeted intracellular proteins were evaluated using molecular docking software such as PyRx, PyMOL, and Ligplot analyzers.
Results: Our findings reveal fascinating affinities and interaction patterns between snake venom proteins and MDR-TB intracellular enzymes. Analysis of the consequences of these interactions and their capacity to impair catalase-peroxidase and RNA polymerase. Results showed that Russell’s viper venom proteins were active against the catalase-peroxidase system, whereas Bothrops jararaca venom proteins were active against the RNA polymerase system.
Conclusion: This wstudyhighlights a prospective approach for advancing anti-tTB agents by usingsnake venom proteins to inhibit the growth, replication,, and transmission of MDR-TB. This will provide a basis for exploring pharmacophore-based medication exploration against MDR-TB infections.