# Targeting Influenza A Virus by a Carbohydrate-inspired Strategy

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $483,750

## Abstract

PROJECT SUMMARY/ABSTRACT
 Protein glycosylation and carbohydrate-mediated recognition events play a major role during
intercellular communications, which can engage components of the immune system and help maintain a
healthy state of the organism. Unfortunately, many viruses can take advantage of protein glycosylation. In the
case of influenza virus, the coat protein hemagglutinin (HA) mediates virus binding to sialoside receptors of the
host cell and facilitates the fusion of viral and host membranes. Since complex-type N-glycosylation of proteins
was shown to be crucial for the influenza virus infectivity, the putative influenza receptor is believed to be a
glycoprotein. Unfortunately, N-glycan samples occupy only a small percentage of the established glycan
collections that are used in the study of influenza virus. The availability of asymmetrically branched N-glycan
samples is instrumental to the development of the next generation diagnostic tools and glycan sequencing
methods. Using the modular method developed by our lab, we will expand the current collections of N-glycan
structures. In order to improve diagnostic capabilities of glycan arrays for the profiling of influenza strains, we
will create N-glycan arrays on the aluminium oxide coated glass (ACG) slides as this technology enables better
control over the glycan density and distribution than conventional N-hydroxysuccinimide activated slides; and
allows detection of even weak carbohydrate-based interactions.
 Synthetic samples of N-glycans will be used to optimize the anti-influenza broadly neutralizing antibody
FI6, thus assisting clinical development of FI6 as universal and highly potent therapeutics of flu infection. The
fragment crystallizable (Fc) region of FI6 contains a single N-glycan at N297, which engage FcγIIIa receptor,
thus activating the antibody-depended cell-mediated cytotoxicity (ADCC) mechanism for neutralization and
clearance of the infected cells.
 The current glycan structure-activity relationship (gSAR) is mostly established for the glycoforms with
bi-antennary glycans, whereas protein glycoforms containing tetra-antennary complex-type N-glycans have not
been accessed yet, even though, increasing the degree of sialylation is expected to improve ADCC and
prolong in vivo half-life of glycoprotein therapeutics. We intend to complete the gSAR of FI6 by preparing
glycoforms with tri- and tetra-antennary complex-type N-glycans, as well as neuraminidase-resistant N-glycan
derivatives. New methods generated by this research and the expanded antibody gSAR will guide the general
design of other therapeutic antibodies targeting cancer, HIV-1 and other pathological conditions, and will have
a direct impact on public health.

## Key facts

- **NIH application ID:** 10239014
- **Project number:** 5R01AI130227-03
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** CHI-HUEY WONG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $483,750
- **Award type:** 5
- **Project period:** 2019-09-18 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239014

## Citation

> US National Institutes of Health, RePORTER application 10239014, Targeting Influenza A Virus by a Carbohydrate-inspired Strategy (5R01AI130227-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10239014. Licensed CC0.

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