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Discovery of Antibody and Peptide Targeting Dengue Virus

As an undisrupted global leader in anti-virus antibody and peptide discovery, Creative Biolabs proudly introduces our innovative platform, Anti-Virus Biomolecular Discovery. Supported by our diverse technologies, we are able to provide the best professional services for the discovery and development of anti-dengue virus biomolecules.

Property of Dengue Virus

Discovery of Antibody and Peptide Targeting Dengue Virus

Dengue virus (DENV) is a relatively simple positive-sense single stranded RNA virus that is 50 nm in diameter and has three structural proteins capsid protein (C), precursor membrane protein (prM) and envelope protein (E), and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). There are four distinct serotypes (DENV 1-4) and several genotypes within each serotype. Since 1950s, there has been considerable expansion in the geographic spread of dengue and exponential rise in disease incidence. It is estimated that the annual global incidence is 390 million cases, of which 96 million are clinically apparent. There are several factors that drive this pandemic, including globalization, the spread of the Aedes mosquito vector, inadequately planned urbanization, and the absence of a licensed vaccine or anti-dengue therapeutics.

Clinical Importance for Discovery of DENV-targeting Antibody/Peptide

Beyond vaccine development, other strategies have been pursued to control DENV infections. A renewed effort has been made in evaluating inhibitors of specific steps in DENV lifecycle. High-throughput antiviral biomolecular discovery screens have been performed to identify inhibitors of the fusogenic viral protein E, the protease and helicase proteins (NS3), integral membrane proteins required for replication (NS2A and NS4B), and the RNA-dependent RNA polymerase and methyltransferase (NS5), with further pre-clinical development ongoing. Nonetheless, because biomolecules against viral proteins could be selected for resistant variants, the concept of targeting host molecules required for DENV infectivity has emerged as an alternative strategy.

DEVN Targets for Antibody and Peptide Discovery

  • E Protein Domain III

    There are three principal domains that make up the immunodominant E glycoprotein monomer, designated E domain I (EDI), EDII, and EDIII. Extensive mapping studies of epitopes recognized by potently neutralizing mouse mAbs have identified several hot spots on all three domains of the E protein. The most potent type-specific murine neutralizing Abs have been shown to bind a region on the lateral surface of the recombinant E protein DIII. As a result of these studies, considerable previous efforts focused on EDIII for possible use as a target for therapeutic antibody/peptide and vaccine discovery and development.

  • prM protein

    prM protein is cleaved by furin protease in the Golgi and falls away when mature virus particles are released from cells. However, prM cleavage is frequently incomplete with a range of partially mature virus forms produced with intermediate levels of prM. This produces a challenge for the host immune response as mature and immature virus particles present markedly different structural determinants at the virion surface. The human host will first be infected by virus injected following an insect bite which has a high prM content but then virus production will be driven from human cells with potentially a lower prM content. The ability to neutralize more mature, low-prM containing viruses, is not possessed by a number of anti-dengue antibodies such as those targeting the FLE or prM.

Discovery of Antibody and Peptide Targeting Dengue VirusFig.1 The protein E dimer epitope (EDE) recognized by the bNAbs (Rouvinski et al. 2015).

DENV Antibody/Peptide Discovery in Creative Biolabs

With years of experience in the field of antibody development, Creative Biolabs has successfully developed an advanced Anti-Virus Biomolecular Discovery, which is optimal for the development of first-in-class neutralizing antibody and peptide. Our in-house scientists can provide the best service to assist your anti-DENV projects. Please contact us for more information and a detailed quote.

Reference:

  1. Rouvinski A.; et al. Recognition determinants of broadly neutralizing human antibodies against dengue viruses. Nature. 2015, 520(7545):109-13.
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