Huan Hu, Qiang Deng, Cheng Guo, Qin Wu, Qianlin Li
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引用次数: 0
Abstract
ZIKA virus (ZIKV), an emerging pathogen for which no licensed drugs or vaccines exist, has attracted global attention. ZIKV envelope protein domainIII (EDIII) can induce neutralizing antibodies with minor cross-reactive epitopes among flaviviruses. Currently, no nanobodies against the ZIKV EDIII protein are available. In our study, 15 nanobodies were derived from a naive phage library. High-affinity and specific nanobodies of Nb-C9, Nb-D8, Nb-E3, and Nb-E5 were selected in vitro showing dissociation constants of 8.24, 6.59, 2.52, and 8.22 nM, respectively. The Nb-E3 and Nb-E5 potently neutralized strain ZIKV-GD01 with plaque reduction neutralization test (PRNT)50 values of 0.1875 and 0.0234 μg/mL, respectively. In addition, a linear epitope Z17-VGEKKITHHWHRS recognized by Nb-E5 showed potential as a candidate for the development of epitope-based vaccines. These findings may contribute to the development of a new therapeutic strategy against ZIKV infection.
期刊介绍：
ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to:
* Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials.
* Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets.
* Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance.
* Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents.
* Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota.
* Small molecule vaccine adjuvants for infectious disease.
* Viral and bacterial biochemistry and molecular biology.
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