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- Title
In Silico Studies of Potential Selective Inhibitors of Thymidylate Kinase from Variola virus.
- Authors
Garcia, Danielle R.; Souza, Felipe R.; Guimarães, Ana P.; Valis, Martin; Pavelek, Zbyšek; Kuca, Kamil; Ramalho, Teodorico C.; França, Tanos C. C.
- Abstract
Continuing the work developed by our research group, in the present manuscript, we performed a theoretical study of 10 new structures derived from the antivirals cidofovir and ribavirin, as inhibitor prototypes for the enzyme thymidylate kinase from Variola virus (VarTMPK). The proposed structures were subjected to docking calculations, molecular dynamics simulations, and free energy calculations, using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method, inside the active sites of VarTMPK and human TMPK (HssTMPK). The docking and molecular dynamic studies pointed to structures 2, 3, 4, 6, and 9 as more selective towards VarTMPK. In addition, the free energy data calculated through the MM-PBSA method, corroborated these results. This suggests that these compounds are potential selective inhibitors of VarTMPK and, thus, can be considered as template molecules to be synthesized and experimentally evaluated against smallpox.
- Subjects
SMALLPOX; MOLECULAR dynamics; KINASE inhibitors; VIRUSES; ENZYME inhibitors; RIBAVIRIN
- Publication
Pharmaceuticals (14248247), 2021, Vol 14, Issue 10, p1027
- ISSN
1424-8247
- Publication type
Article
- DOI
10.3390/ph14101027