# Targeting Influenza A Virus by a Carbohydrate-inspired Strategy

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2024 · $452,500

## Abstract

Project Summary:
There have been four influenza outbreaks that caused global pandemics causing major threats to public health.
Although influenza vaccines have been available for protection, current vaccines are strain-specific and require
annual renewal, whereas the development of antiviral drugs encountered the problem of drug resistance. In
addition to improving the prevention and treatment of flu, developing a rapid and precise method for detecting
specific influenza variants could assist prophylactic measures, and glycan arrays have been an effective tool to
meet this purpose. During influenza infection, the virus surface hemagglutinin first interacts with a sialoside
receptor on the respiratory tract followed by neuraminidase-mediated cleavage of sialic acid from the receptor
for viral entry. Determining the precise structure of the sialoside receptor and the detailed mechanism of infection
will facilitate the development of better diagnostic methods. Unfortunately, current N-glycan samples occupy only
a small percentage of the glycans required for the study of the influenza virus. The availability of asymmetrically
branched N-glycans is instrumental to the development of next-generation diagnostic tools and glycan
sequencing methods. The improved chemoenzymatic and modular strategies developed in this study will enable
the previously infeasible synthesis of complex glycans commonly found in the respiratory tract but absent in the
current arrays. These complex glycans will be used to create a comprehensive glycan array, thus advancing our
understanding of the precise binding specificity of HA subtypes and the rapid detection of influenza variants.
Monoclonal antibodies have been used for the treatment of life-threatening diseases, including viral infections.
While the Fab region defines antibody specificity against viral targets, the Fc region recruits immune cells to fight
infection. In particular, the function of a single N-glycan at N297 of Fc is to engage FcγRIIIA and FcγRIIA
receptors, activating the antibody-depended cell-mediated cytotoxicity (ADCC) and the long-lasting vaccinal
effect respectively for neutralization and clearance of infected cells. We have identified the α2,6-sialylated
complex type biantennary glycan without core fucose (SCT) as an optimal modification for the broadly
neutralizing anti-influenza antibody FI6 to exhibit the best ADCC and vaccinal effect. In this study, we will
evaluate the 7F-SCT glycoform of FI6, which is stable toward sialidase degradation and is expected to have
optimal effector functions yet can be synthesized enzymatically.
We anticipate that the strategies and methods developed in this study will further transform the field of influenza
research and glycoscience enabling access to multi-antennary N-glycans and precise arrays for the study of HA
binding specificity and evaluation of homogenous antibodies against influenza infection.

## Key facts

- **NIH application ID:** 10878261
- **Project number:** 2R01AI130227-05A1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** CHI-HUEY WONG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $452,500
- **Award type:** 2
- **Project period:** 2019-09-18 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878261

## Citation

> US National Institutes of Health, RePORTER application 10878261, Targeting Influenza A Virus by a Carbohydrate-inspired Strategy (2R01AI130227-05A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10878261. Licensed CC0.

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