Authors:
Kim Rafaelle E. Rafaelle E. Reyes
;
Timothy Jen R. Roxas
;
Marineil C. Gomez
and
Lemmuel L. Tayo
Affiliation:
School of Chemical, Biological, and Materials Engineering and Sciences, Mapúa University, 658 Muralla Street, Intramuros, Manila, Philippines
Keyword(s):
African Swine Fever virus, ADME/T, In Silico, De Novo, Drug-likeness, pA104R, Molecular Docking, Ligand-based Virtual Screening.
Abstract:
African Swine Fever Virus (ASFV) is a dsDNA virus causative of the African Swine Fever (ASF) in wild and domestic hogs. ASF is characterized by hemorrhagic fever, high mortality, and transmissibility. The binding of the DNA to the pA104R protein mediates viral replication and genome packaging. In the present study, we generated nine (9) reference compounds that exhibited high docking affinities through de novo computer-aided drug design (CADD). These compounds were then used as query molecules to find commercially available drug-like compounds using ligand-based virtual screening (VS). We were able to retrieve 900 hit compounds that exhibited the same pharmacophoric activities. Then, these hit compounds were subjected to drug-likeness filtration to identify the most likely to be developed as commercial drugs based on established parameters. We identified sixty-two (62) drug-like molecules. Molecular docking was then performed to determine the top five compounds with the highest bindi
ng affinities against the target protein. ADME/T profiling was done on these compounds to assess their pharmacokinetic properties. Compound 8.45 performed best based on our devised scoring system. This paper shall serve as a good reference in the discovery and development of anti-ASFV therapeutics.
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