The ESX-1 secretion system of Mycobacterium tuberculosis delivers bacterial virulence factors to host cells during infection. The most abundant factor, the ESAT-6/CFP-10 dimer, is targeted for secretion via a C-terminal signal sequence on CFP-10 that is recognized by the cytosolic ATPase, Rv3871. ATPase that is a component of the ESAT-6/CFP-10 secretion system. ESX locus contains genes encoding conserved secretion machinery components termed EccCb1. these core components are required for ESAT-6/CFP-10 secretion [70, 71]. Rv3871 is a cytoplasmic protein connected with the Rv3870 and encoded by the EccCb1 gene. These proteins supply energy for the secretion process. Each of these ATPases is involved in targeting protein for ESX-1 secretion. EccCb1 binds a seven amino acid C-terminal signal peptide of CFT- 10, which is required for secretion of the ESAT-6/CFP-10 complex. In this we target the Rv3871 seven amino acid c-terminal region and block it through multiple drugs so, it cannot be activated by the ATPases and not to supply energy for the secretion protein during infection (Tuberculosis). In the present study we have comparatively studied different Rv3871 inhibitory antagonist drug molecule which could be a potential drug molecule to inhibit ATPases on the Rv3871 molecule that is responsible for the energy supply. We have 16 antagonistic drug molecules as shortlisted based on previous studies, that block the target site on the Rv3871 molecule.