Estudos de relação estrutura atividade e docking - UFRJ

ixABSTRACTHerpes simplex is one of the most common infections oh humanity. The disease iscaused by the herpes simplex virus (HSV), which is classified in type 1 and type 2, amongothers. Type 1 is mainly associated with facial infections and type 2, with genital infections.Studies have shown that several viruses codifies one or more proteases, enzymes that arerequired for new infectious virions production. This works shows the analysis of theinteractions between the HSV-1 protease and benzoxazinones derivatives throughtcomparative modeling and molecular docking studies. After that, there were performeddruglikeness and drogscore studies of the most potent derivatives in order to design newcompounds candidates to the anti-HSV-1 therapy. Two compounds of the benzoxazinonesseries, 26 and 29, showed interactions with important residues for catalytic activity of HSV-1protease. These compounds were analysed on the Druglikeness and Drugscore studies whichshowed the compound 29 with the best results, despite exhibiting the second better activity.These compounds afforded four new molecules candidates to the anti HSV-1 therapy, inwhich one (34) showed promising molecular docking result, with interactions between theligand and the residues Ser129, Thr132 and Arg157, importants for the protease activity. Theinteractions described indicate that the replacement of an atom of cloro for an atom of bromoin the R 4 position of the new compound could increase the activity of the benzoxazinone 26,revealing a new prototype candidate for the anti HSV-1 therapy.Keywords: Protease; Herpesvirus; Comparative modeling; Molecular Docking;Benzoxazinones.