Herpes simplex virus infections have been described in the medical literature for centuries, yet the the drugs available nowadays for therapy are largely ineffective and low oral bioavailability plays an important role on the inefficacy of the treatments. Additionally, the details of the inhibition of Herpes Virus type 1 are still not fully understood. Studies have shown that several viruses encode one or more proteases required for the production new infectious virions. This study presents an analysis of the interactions between HSV-1 protease and benzoxazinone derivatives through a combination of structure-activity relationships, comparative modeling and molecular docking studies. The structure activity relationship results showed an important contribution of hydrophobic and polarizable groups and limitations for bulky groups in specific positions. Two Herpes Virus type 1 protease models were constructed and compared to achieve the best model which was obtained by MODELLER. Molecular docking results pointed to an important interaction between the most potent benzoxazinone derivative and Ser129, consistent with previous mechanistic data. Moreover, we also observed hydrophobic interactions that may play an important role in the stabilization of inhibitors in the active site. Finally, we performed druglikeness and drugscore studies of the most potent derivatives and the drugs currently used against Herpes virus.

A Cardiomiopatia Chagásica compromete o músculo cardíaco do indivíduo infectado e, dentre as complicações cardíacas presentes, a de maior importância é a Insuficiência Cardíaca Congestiva. O tratamento farmacológico tem a finalidade de impedir o progresso das complicações da forma cardíaca e manter a função cardíaca, pois as agressões cardíacas, desencadeadas pela resposta imune do indivíduo infectado, favorecem eventos de necrose, fibrose, arritmias e tromboembolismo, que podem culminar com o óbito do paciente chagásico. O objetivo deste estudo foi descrever a cardiomiopatia chagásica, bem como o tratamento disponível para esta patologia. O tratamento da doença de Chagas está restrito a apenas dois medicamentos, sendo apenas um deles, produzido no Brasil, o Benznidazol. Quase 110 anos após sua descoberta, a Doença de Chagas ainda apresenta um alto índice de morbimortalidade. Observou-se que a terapia farmacológica disponível é restrita e não específica para a doença.