Virtual Screening of CPP Conjugated Peptide as QcrB BCC Protein Inhibitors of Mycobacterium tuberculosis Bacteria

Abstract

Tuberculosis is a global leading cause of death, just below COVID-19 and ranked above HIV. This disease is caused by a pathogen called Mycobacterium tuberculosis, which spreads easily through the air and is known to remain latent in most people's bodies, about a quarter of the world's population. The current problems with TB also include two main concerns: The official vaccine is ineffective and the bacteria keep gaining resistance to drugs. In this research, we proposed a strategy to create a new drug to overcome this resistance by simulating it through in silico methods by running molecular docking through Molecular Operating Environment (MOE) software, dynamic simulation through the iMODS website, and pharmacological prediction by comparing it through multiple pharmacophore predictors (AdmetSAR, SwissAdme, and pkCSM). We proposed five peptide drugs (Noopept, Glycyl-L-Proline, Leuteonosticon, Alaptide, dan NNZ-2591) that were then conjugated with a Cell-Penetrating Peptide (CPP) known for its transference prowess, with the receptor of QcrB protein, a complex related to the enzyme responsible for respiration and electron transference in MTB, which can prevent the bacteria development when inhibited. All candidates were picked following the rule of five proposed by Lipinski along with ADME and toxicity evaluation, with models and structures gained from the PubChem database. This research hopes to propose a way of combating drug-resistant TB by using a specified target and CPP for breaking the bacteria's lines of defense.