A quantum chemistry investigation of a potential inhibitory drug against the dengue virus

We present an in silico study of the interaction energy between NS2B-NS3, a serine protease of the dengue virus (DENV), and the inhibitor benzoyl-norleucine-Lys-Arg-Arg-aldehyde (Bz-nKRR-H), a crucial step in the design and development of dengue's antiviral drugs, using quantum chemistry calculations based on the density functional theory (DFT) at the generalized gradient approximation (GGA). The interaction energies between the inhibitor Bz-nKRR-H and each amino acid belonging to the binding site was calculated through the molecular fragmentation with conjugate caps (MFCC) approach employing a dispersion corrected exchange-correlation functional. Besides the interaction energy, we also calculated the distances, types of molecular interactions, and the atomic groups involved in the process. Our results show that the interaction energy of the system reached convergence at 15.0 Å, with the central residues identified in this interaction radius, as well as their attraction/repulsion energies, all of them being important inputs to improve the effectiveness of antiviral drugs to avoid the dissemination of the dengue virus. The total interaction energy of the inhibitor Bz-nKRR-H bound to a serine protease of the dengue virus is mainly due to the action of Asn152, Met49, Tyr161, Asp129 and Gly151 (Met84, Met75, Asp81, Asp79 and Asp80) residues at the NS3 (NS2B) subunit.