DESIGN OF A CONCEPTUAL ANTIVIRAL STRATEGY TO TREAT WEST NILE VIRUS INFECTION

Abstract

RECENT OUTBREAKS OF WEST NILE DISEASE CONTINUE TO UNDERSCORE THE MEDICAL IMPORTANCE OF WEST NILE VIRUS (WNV). NO HUMAN VACCINE NOR THERAPEUTIC HAS BEEN APPROVED. IN THIS PROJECT, A NOVEL ANTIVIRAL IS ENGINEERED TO INDUCE ANTIVIRAL IFN-STIMULATED GENES VIA A PHARMACOPHORE PROTEIN, DELIVERED BY A PROPRIETARY CELL-PENETRATING PEPTIDE (FPCPP). A WARHEAD COMPONENT, COMPRISING OF A SINGLE-CHAIN VARIABLE FRAGMENT THAT BOUND SPECIFICALLY TO WNV ENVELOPE GLYCOPROTEIN DOMAIN III (E-DIII), WAS INCORPORATED FOR SELECTIVE DELIVERY INTO NEWLY INFECTED CELLS.

HERE, DERIVATION AND VALIDATION OF INDIVIDUAL ANTIVIRAL COMPONENTS WERE ALSO DETAILED. THE PHARMACOPHORE WAS SHOWN TO OVERCOME WNV INNATE IMMUNITY EVASION AND BLOCKAGES AND LOWER VIRUS TITRE, WHILE FPCPP WAS SHOWN TO DELIVER FUNCTIONAL PROTEINS INTO CELLS. RECOMBINANT E-DIII (RE-DIII) PROTEIN WAS EXPRESSED AND PURIFIED TO GENERATE MONOCLONAL ANTIBODIES, FROM WHICH THE WARHEAD WAS DERIVED. THE PHARMACOPHORE AND WARHEAD WERE LASTLY EXPRESSED WI