Quest for Novel Plant based Therapeutic Options Against Dengue Virus NS2B-NS3 protease: An integrative computational methodology

Abstract

Abstract The Dengue virus (DENV) has caused heavy concern worldwide because of its high infectivity and mortality rate. Still, there's no specific drug or preventive medication to treat DENV infection despite comprehensive analysis by the researchers. This study was designed to demonstrate the efficacy of some plant-derived bioactive compounds against DENV by using ligand-based virtual screening methods. A total of 52 plant metabolites and 74 plant peptides were screened on the basis of their reported pharmacological activities against DENV NS2B-NS3 protease(4M9T) employing a molecular docking approach. Furthermore, the ADMET properties were also predicted for screened top candidates i.e., gossypol, theaflavin, cycloviolacin O24,and cycloviolacin H3. Results showed that screened top candidates i.e., gossypol, theaflavin, cycloviolacin O24, and cycloviolacin H3 provide the highest binding affinity to the targeted DENV protein. The Crucial binding sites, as well as drug surfacehotspots were unraveled for viral targeted protein. The analysis of ADME properties exhibited that none of the compounds had side effects that would reduce their drug-like properties. As compared, the toxicity pattern analysis has unmasked the non-toxic essence of screened drug candidates. The NMA analysis revealed the docked complex was compact and it demonstrated its resistance to deformation. These results may lead to the development of effective anti-DENV natural medicines. Further in vivo trials are strongly recommended.