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Occupation of a thermoresistant-scaffold (αRep) at SP1-NC cleavage site disturbs the function of HIV-1 protease
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Metadata
Document Title
Occupation of a thermoresistant-scaffold (αRep) at SP1-NC cleavage site disturbs the function of HIV-1 protease
Author
Hadpech S., Peerakam N., Chupradit K., Tayapiwatana C.
Name from Authors Collection
Affiliations
Faculty of Pharmaceutical Sciences, Burapha University, Chon Buri, 20131, Thailand; Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand; Biomedical Technology Research Center, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
Type
Article
Source Title
Bioscience Reports
ISSN
01448463
Year
2020
Volume
40
Issue
6
Open Access
Gold, Green
Publisher
Portland Press Ltd
DOI
10.1042/BSR20201131
Abstract
HIV-1 nucleocapsid (NC) becomes an attractive target for the development of novel anti-HIV-1 agents. Discovering of non-antibody scaffolds that disrupt the function of NC will be a potential aspect for disturbing viral maturation process. Correspondingly, we explored the specific binding site of the thermoresistant-scaffold protein, αRep9A8 which formerly demonstrated the inhibitory effect on HIV-1 replication. The portion of Gag, CA21-SP1-NC has been used as a template for designing nine overlapping peptides (P4-P12). The P9 peptide showed the strongest binding activity followed by P8 and P12 respectively. The amino acid sequences on those peptides resemble the N-terminal domain of the NC proximity to the SP1-NC initial cleavage site and across the conserved CCHC zinc finger 1 (ZF1) of NC. The interaction KD between αRep9A8 with its target was 224.9 +− 57.4 nM. Consequently, αRep9A8 demonstrated the interference of the HIV-1 protease function by hindering a protease cleavage site. The released NC product from CA21-SP1-NC was diminished. The present study provided an additional information of αRep9A8 function in interfering of viral maturation processes resulting in the decremental efficiency of viral infectivity. © 2020 Portland Press Ltd. All rights reserved.
Funding Sponsor
Chiang Mai University; National Research Council of Thailand
License
CC BY
Rights
Author
Publication Source
Scopus