Small-molecule docking, Molecular Dynamics, and classical and quantum mechanics binding free energy calculation to identify novel bovine viral diarrhea envelope protein inhibitors

MARIELA BOLLINI; M. GABRIELA AUCAR; FERNANDO MERWAISS; NATALIA S. ADLER; EMILSE S. LEAL; GABRIELA A. FERNÁNDEZ; MARÍA J. PASCUAL; CLAUDIO N. CAVASOTTO; DIEGO E. ALVAREZ

Santos (SP)

Congreso; XLII Congreso da Sociedade de Biofísica (SBBf); 2017

Bovine viral diarrhea virus (BVDV) is a member of the genus Pestivirus within the family Flaviviridae. Pestiviruses, including BVDV, border disease virus, and classical swine fever virus, are important animal pathogens. BVDV causes both acute and persistent infections in cattle, leading to substantial financial losses within the livestock industry each year. The global prevalence of persistent BVDV infection and the lack of a highly effective antiviral therapy have spurred intensive efforts to discover and develop novel anti-BVDV therapy in the pharmaceutical industry. Antiviral targeting of virus envelope proteins is an effective strategy for therapeutic intervention of viral infections. In this work, we performed prospective docking-based virtual screening to identify small molecules that likely bind to the region surrounded by domains I and II of the envelope protein of BVDV. Several structurally different compounds were identified and two of them had EC50 values in the low-micromolar range. Molecular dynamics simulations, and classical and quantum mechanics binding energy predictions were used in an attempt to characterize the interaction of active inhibitors with protein E2. These findings could offer a better understanding of binding determinants of BVDV inhibitors, as well as benefit the discovery of novel and more potent BVDV inhibitors.