from patients without a history of previous treatment should be referred to as 'drug resistance among new cases' (instead of 'primary resistance').
To achieve the structural basis to improve antimycobacterial activity, the dynamic behavior of arylamide inhibitors and a substrate, -acetylcysteamine)-thioester, were carried out by molecular dynamics (MD) simulations.
Results show that isonicotinic acyl-NADH (INADH) has an extremely high binding affinity toward the wild type Inh A by forming stronger interactions compared to the parent drug (isoniazid) (INH).
Due to the increase of hydrophobicity and reduction in the side chain's volume of A94 of mutant type Inh A, both INADH and the mutated protein become more mobile.
to antimycobacterial drugs is the consequence of spontaneous mutations in genes that encode either the target of the drug, or enzymes that are involved in drug activation.
Resistance-associated point mutations, deletions, or insertions have been described for all first-line drugs (isoniazid, rifampin, pyrazinamide, ethambutol, and streptomycin), and for several second-line and newer drugs (ethionamide, fluoroquinolones, macrolides, nitroimidazopyrans) .]]