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

BOLLINI, MARIELA; LEAL, EMILSE S.; ADLER, NATALIA S.; AUCAR, MARÍA G.; PASCUAL, MARÍA J.; FERNANDEZ, G.A.; MERWAISS, F.; ALVAREZ, DIEGO E.; CAVASOTTO, CLAUDIO N.

Santos (SP)

Congreso; XLII Congress of the Brazilian Biophysics Society (SBBf); 2017

Bovineviral diarrhea virus (BVDV) is a member of the genus Pestivirus within thefamily Flaviviridae. Pestiviruses, including BVDV, border disease virus, andclassical swine fever virus, are important animal pathogens. BVDV causes bothacute and persistent infections in cattle, leading to substantial financiallosses within the livestock industry each year. The global prevalence ofpersistent BVDV infection and the lack of a highly effective antiviral therapyhave spurred intensive efforts to discover and develop novel anti-BVDV therapyin the pharmaceutical industry. Antiviral targeting of virus envelope proteinsis an effective strategy for therapeutic intervention of viral infections. Inthis work, we performed prospective docking-based virtual screening to identifysmall molecules that likely bind to the region surrounded by domains I and IIof the envelope protein of BVDV. Several structurally different compounds wereidentified and two ofthem had EC50 values in the low-micromolar range. Molecular dynamicssimulations, andclassical and quantum mechanics binding energy predictions were used in anattempt to characterize the interaction of active inhibitors with protein E2.These findings could offer a better understanding of binding determinants ofBVDV inhibitors, as well as benefit the discovery of novel and more potent BVDVinhibitors.