Comparative in Silico Study of Congocidine Congeners as Potential Inhibitors of African Swine Fever Virus
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Date
2019
Authors
Kinyanyi, Dickson
Amwayi, Peris
Wamalwa, Mark
Obiero, George
Journal Title
Journal ISSN
Volume Title
Publisher
PLoS ONE
Abstract
Abstract
African swine fever virus (ASFV) infection is fatal in domesticated pigs, with a mortality rate
approaching 100%. This may result in economic losses and threats to food security. Cur rently, there are no approved vaccines or antiviral therapies for ASFV. Therefore, in this
study, we evaluated congocidine congeners and a tris-benzimidazole as potential inhibitors
of ASFV transcription using an in silico approach. We applied redocking of congocidine and
docking of its congeners and a tris-benzimidazole to a receptor containing B-DNA with AT motifs as a target to mimic conserved ASFV late gene promoters. Subsequently, the binding
scores of DNA-ligand docked complexes were evaluated and their binding affinity was esti mated. Molecular dynamics (MD) simulation was then used to assess ligand behavior within
the minor groove. From our results, it is evident the less toxic congocidine congeners and
tris-benzimidazole could dock to AT-rich regions significantly. Additionally, the predicted
binding affinities had suitable values comparable to other experimentally determined minor
groove binders, MD simulation of the docked DNA-ligand complexes and subsequent
molecular trajectory visualization further showed that the ligands remained embedded in the
minor groove during the time course of simulation, indicating that these ligands may have
potential applications in abrogating ASFV transcription.
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Citation
Kinyanyi D, Amwayi P, Wamalwa M, Obiero G (2019) Comparative in silico study of congocidine congeners as potential inhibitors of African swine fever virus. PLoS ONE 14(8): e0221175.