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Discovery of Neutralizing Antibody (NAb) and Peptide Targeting Zika Virus

Creative Biolabs has over a decade of working experience in Anti-Virus Biomolecular Discovery. Based on our advanced AntInfect™ Platform, our seasoned scientists can offer high-quality Zika virus (ZIKV) neutralizing antibody and ZIKV-specific peptide discovery services. We are confident in providing customers with the best service at the most competitive cost.

The Properties of Zika Virus

Discovery of Neutralizing Antibody (NAb) and Peptide Targeting Zika Virus

As a member of the Flavivirus genus, ZIKV is enveloped and icosahedral and has a non-segmented, single-stranded, positive-sense RNA genome. ZIKV can be classified into three phylogenetic lineages, East African, West African and Asian, and is transmitted primarily through the bite of an infected Aedes mosquito, with evidence also supporting sexual transmission similar to other flaviviruses. Common symptoms of infection with the virus include mild headaches, maculopapular rash, fever, malaise, conjunctivitis, and joint pains. ZIKV has been shown to cause microcephaly in babies exposed in utero.

Urgent Need for ZIKV-Specific Diagnostics and Therapeutics

Infection by ZIKV can be difficult to distinguish from infection by other mosquito-borne Flaviviruses due to high sequence similarity, serum antibody cross-reactivity, and virus co-circulation in endemic areas. Indeed, existing serological methods are not able to consistently differentiate ZIKV from other Flaviviruses, which makes it extremely difficult to accurately calculate the incidence rate of Zika-associated Guillain-Barre in adults, microcephaly in newborns, or asymptomatic infections within a geographical area. Thus, there is an urgent need for a specific high-throughput diagnostic assay to discriminate ZIKV infections from other Flavivirus infections. Moreover, specific vaccines or antiviral drugs are urgently needed to prevent or treat ZIKV infection. The good news is that Zika-specific peptide as well as neutralizing antibody could be developed as useful serology reagents or anti-viral drugs.

Targets of ZIKV Neutralizing Antibody Development

The ZIKV genome encodes a single, large polyprotein, which is proteolytically processed to yield three structural proteins (envelope, E; membrane precursor, PrM; and capsid C) and seven non-structural (NS) proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b, and NS5). Neutralizing antibodies have important roles in the protection against infection by ZIKV. Targets of ZIKV neutralizing antibody include but are not limited to:

  • E protein

Sequence and location of Z2 in the stem region of ZIKV E protein Fig.1 Sequence and location of Z2 in the stem
region of ZIKV E protein (Yu, 2017).

E protein is divided into three domains: a central β-barrel domain [domain I (DI)], an extended dimerization domain (DII), and an immunoglobulin-like segment (DIII). The distal end of DII contains the fusion loop (FL), a hydrophobic sequence that inserts into the host cell endosomal membrane during pH-dependent conformational changes that drive fusion. The E protein is a primary antigenic target of neutralizing antibodies, which binds epitopes in all three structural domains, with many type-specific protective antibodies recognizing determinants in DIII.

  • NS proteins

NS proteins are thought to co-translationally assemble on the endoplasmic reticulum (ER) membranes forming the replication competent complex, which consists morphologically distinct, membrane-bound compartments that also differ with respect to both function and NS proteins composition. NS1 protein is involved in many steps of the flavivirus life cycle, including viral replication, immune evasion, and pathogenesis. As the only viral protein which can be secreted into the extracellular space, the nonstructural protein NS1 plays diverse roles in immune evasion via binding to complement proteins and modifying or antagonizing their functions. The NS3 and NS5 proteins are central to the viral RC, as together they harbor most, if not all, of the catalytic activities required to both caps and replicate the viral RNA. NS3 is a multidomain protein, with an N-terminal NS3Pro as discussed above, and a C-terminal portion containing the RNA triphosphatase (NS3RTPase) and RNA helicase (NS3Hel) activities involved in capping and viral RNA synthesis, respectively.

ZIKV Neutralizing Antibody and Specific Peptide Discovery Service in Creative Biolabs

Creative Biolabs has successfully developed an advanced AntInfect™ Platform, which is optimal for neutralizing antibody and function peptide discovery. Our seasoned scientists provide high-quality ZIKV NAbs discovery service for all our global customers. For functional peptide discovery, we have applied the cutting-edge high-density peptide microarrays and phage display technologies to identify ZIKV-specific peptides, which can be developed to serology reagents or anti-viral drugs.

We offer turn-key or ala carte services customized to our client’s needs. Please contact us for more information and a detailed quote.

References:

  1. Yu, Y.; et al. A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses. Nat Commun. 2017, 8:15672.
  2. Zhao, H.; et al. Structural basis of Zika virus-specific antibody protection. Cell. 2016, 166(4):1016-1027.
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