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Title: Humanized-V<inf>H</inf>H transbodies that inhibit HCV protease and replication
Authors: Surasak Jittavisutthikul
Jeeraphong Thanongsaksrikul
Kanyarat Thueng-In
Monrat Chulanetra
Potjanee Srimanote
Watee Seesuay
Aijaz Ahmad Malik
Wanpen Chaicumpa
Mahidol University
Thammasat University
Kasetsart University
Keywords: Immunology and Microbiology;Medicine
Issue Date: 20-Apr-2015
Citation: Viruses. Vol.7, No.4 (2015), 2030-2056
Abstract: © 2015 by the authors; licensee MDPI, Basel, Switzerland. There is a need for safe and broadly effective anti-HCV agents that can cope with genetic multiplicity and mutations of the virus. In this study, humanized-camel VHHs to genotype 3a HCV serine protease were produced and were linked molecularly to a cell penetrating peptide, penetratin (PEN). Human hepatic (Huh7) cells transfected with the JFH-1 RNA of HCV genotype 2a and treated with the cell penetrable nanobodies (transbodies) had a marked reduction of the HCV RNA intracellularly and in their culture fluids, less HCV foci inside the cells and less amounts of HCV core antigen in culture supernatants compared with the infected cells cultured in the medium alone. The PEN-VHH-treated-transfected cells also had up-regulation of the genes coding for the host innate immune response (TRIF, TRAF3, IRF3, IL-28B and IFN-β), indicating that the cell penetrable nanobodies rescued the host innate immune response from the HCV mediated-suppression. Computerized intermolecular docking revealed that the VHHs bound to residues of the protease catalytic triad, oxyanion loop and/or the NS3 N-terminal portion important for non-covalent binding of the NS4A protease cofactor protein. The so-produced transbodies have high potential for testing further as a candidate for safe, broadly effective and virus mutation tolerable anti-HCV agents.
ISSN: 19994915
Appears in Collections:Scopus 2011-2015

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