Flavonoids as Multi-target Inhibitors for Proteins Associated with Ebola Virus: In Silico Discovery Using Virtual Screening and Molecular Docking Studies.
Ebola virus is a single-stranded, negative-sense RNA virus that causes severe hemorrhagic fever in humans and non-human primates. This virus is unreceptive to a large portion of the known antiviral drugs, and there is no valid treatment as on date for disease created by this pathogen. Looking into its ability to create a pandemic scenario across globe, there is an utmost need for new drugs and therapy to combat this life-threatening infection. The current study deals with the evaluation of the inhibitory activity of flavonoids against the four selected Ebola virus receptor proteins, using in silico studies. The viral proteins VP40, VP35, VP30 and VP24 were docked with small molecules obtained from flavonoid class and its derivatives and evaluated on the basis of energetics, stereochemical considerations and pharmacokinetic properties to identify potential lead compounds. The results showed that both top-ranking screened flavonoids, i.e., Gossypetin and Taxifolin, showed better docking scores and binding energies in all the EBOV receptors when compared to those of the reported compound. All the screened flavonoids have known antiviral activity, acceptable pharmacokinetic properties and are being used on human and thus can be taken as anti-Ebola therapy without the time lag for clinical trial.
Bioinformatics Division, Indian Institute of Information Technology, Allahabad, India. utkarsh.iiita@gmail.com.
Utkarsh
U
Raj
Bioinformatics Division, Indian Institute of Information Technology, Allahabad, India.
Pritish Kumar
PK
Varadwaj
D000998:Antiviral Agents / Q000494:pharmacology*; D029043:Ebolavirus / Q000187:drug effects* / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
D000998:Antiviral Agents; D005419:Flavonoids; D014764:Viral Proteins; D011794:Quercetin; C003377:taxifolin; C059922:gossypetin
Docking; Ebola virus; Flavonoids; Gossypetin; Pharmacokinetic; Taxifolin; Virtual screening