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Molecules 2015, 20(6), 10689-10704; doi:10.3390/molecules200610689

Computational Studies of Benzoxazinone Derivatives as Antiviral Agents against Herpes Virus Type 1 Protease

Laboratory of Molecular Modeling & QSAR Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21.944-970, RJ, Brazil
Laboratory of Computational Medicinal Chemistry, Faculty of Pharmacy, Fluminense Federal University, Niterói 24.241-000, RJ, Brazil
Laboratory of Antibiotics, Biochemistry, Education and Molecular Modeling, Institute of Biology, Fluminense Federal University, Niterói 24.210-130, RJ, Brazil
Laboratory of Industrial Pharmaceutical Technology, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21.944-970, RJ, Brazil
Authors to whom correspondence should be addressed.
Academic Editor: Rino Ragno
Received: 28 February 2015 / Revised: 27 May 2015 / Accepted: 1 June 2015 / Published: 10 June 2015
(This article belongs to the Special Issue Molecular Docking in Drug Design)
View Full-Text   |   Download PDF [2684 KB, uploaded 10 June 2015]   |  


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. View Full-Text
Keywords: herpesvirus; protease; molecular docking; comparative modeling; benzoxazinones herpesvirus; protease; molecular docking; comparative modeling; benzoxazinones

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Mello, J.F.R.; Botelho, N.C.; Souza, A.M.T.; Oliveira, R.; Brito, M.A.; Abrahim-Vieira, B.A.; Sodero, A.C.R.; Castro, H.C.; Cabral, L.M.; Miceli, L.A.; Rodrigues, C.R. Computational Studies of Benzoxazinone Derivatives as Antiviral Agents against Herpes Virus Type 1 Protease. Molecules 2015, 20, 10689-10704.

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