Biomolecular Interaction of Carnosine and Anti-TB Drug: Preparation of Functional Biopeptide-Based Nanocomposites and Characterization through In Vitro and In Silico Investigations

Host-directed therapies (HDTs) resolve excessive inflammation during tuberculosis (TB) disease, which leads to irreversible lung tissue damage. The peptide-based nanostructures possess intrinsic anti-inflammatory and antioxidant properties among HDTs. Native carnosine, a natural dipeptide with superior self-organization and functionalities, was chosen for nanoformulation. In the present work, multiscale self-assembly approaches of carnosine were developed using a solvent-mediated process (hexafluoro-2-propanol) and further linked with first-line anti-TB drugs. The organofluorine compound in a solvent is attributed to the self-assembling process with heteroatom acceptors in carnosine. In the carnosine-anti-TB drug nanocomposite, the functional moieties represent the involvement of hydrogen bonding and the electrostatic force of attraction. The minimum inhibitory concentration of carnosine-anti-TB drug composites represents an antimycobacterial effect on par with standard drugs. The silicon findings complemented the in vitro results through quantum chemical simulations, elucidating the respective binding pockets between putative <i>Mtb</i> drug targets and carnosine-anti-TB composites. These findings confirmed that the carnosine and anti-TB drug nanocomposites prepared through a solvent-mediated process act as a rational design for functional nanodelivery systems for sustainable TB therapeutics.