Name
Investigation of potential inhibitors targeting rotavirus VP8*-HBGA interaction through molecular docking
Presenter
Kebareng Rakau, Diarrhoeal Pathogens Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria, South Africa
Co-Author(s)
Xi Jiang, Division of infectious diseases, Cincinnati Children’s Hospital Medical Center, Ohio, United States of America & Department of Paediatrics, College of Medicine, University of Cincinnati, United States of America
Ming Tan, Division of infectious diseases, Cincinnati Children’s Hospital Medical Center, Ohio, United States of America & Department of Paediatrics, College of Medicine, University of Cincinnati, United States of America
Mapaseka Seheri, Diarrhoeal Pathogens Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria, South Africa
Abstract Category
Combatting and Exploiting dsRNA viruses
Abstract
Rotaviruses are a leading cause of viral gastroenteritis in children under five years. Despite the availability and usage of four licensed rotavirus vaccines, outbreaks still occur. The virus enters host cells via VP8*, which binds to Histo-blood group antigens (HBGAs) on epithelial cells. Targeting VP8* with small compounds could block entry and serve as potential antiviral strategy. This study employed molecular docking to identify compounds capable of inhibiting VP8*-HBGA interactions.
The VP8* structures of of P[6] and P[8] were obtained from the RCSB protein databank. A library of 6837 commercially available compounds were retrieved from ZINC15 database. Protein preparation was conducted using BIOVIA Discovery Studio Visualizer 2021. And virtual screening was performed with PyRx Virtual Screening Tool using Autodock VINA. Docking scores were used to identify potential inhibitors, with lower scores indicating strong binding affinity. Molecular interactions were analysed using Discovery Studio and top compounds were evaluated for drug-likeness and pharmacokinetic properties using the SwissADME online server.
The docked compounds exhibited moderate binding affinity (<-8.0 Kcal/mol), 11 compounds showed affinity for P[6] VP8* and one for P[8] VP8*. These compounds formed stable hydrogen and ionic bonds with amino acids involved in HBGA recognition. Eight of the 11 compounds satisfied the Lipinski’s rule of five for oral bioavailability. Furthermore, none of the compounds could penetrate the blood-brain barriers except for Tirilizad. Some compounds had low gastrointestinal absorption while a few inhibited cytochrome P450.
The identified compounds show potential as antiviral agents against rotavirus and their effectiveness should be in invitro studies.
The VP8* structures of of P[6] and P[8] were obtained from the RCSB protein databank. A library of 6837 commercially available compounds were retrieved from ZINC15 database. Protein preparation was conducted using BIOVIA Discovery Studio Visualizer 2021. And virtual screening was performed with PyRx Virtual Screening Tool using Autodock VINA. Docking scores were used to identify potential inhibitors, with lower scores indicating strong binding affinity. Molecular interactions were analysed using Discovery Studio and top compounds were evaluated for drug-likeness and pharmacokinetic properties using the SwissADME online server.
The docked compounds exhibited moderate binding affinity (<-8.0 Kcal/mol), 11 compounds showed affinity for P[6] VP8* and one for P[8] VP8*. These compounds formed stable hydrogen and ionic bonds with amino acids involved in HBGA recognition. Eight of the 11 compounds satisfied the Lipinski’s rule of five for oral bioavailability. Furthermore, none of the compounds could penetrate the blood-brain barriers except for Tirilizad. Some compounds had low gastrointestinal absorption while a few inhibited cytochrome P450.
The identified compounds show potential as antiviral agents against rotavirus and their effectiveness should be in invitro studies.