# RP5: Nanobody therapeutics against henipaviruses, arenaviruses, and structural characterization

> **NIH NIH U19** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2024 · $4,640,497

## Abstract

Abstract
The COVID-19 pandemic has emphasized the pressing need for rapid drug development and novel antiviral
therapies. Nanobodies, derived from camelid animals, show promise as small antigen-binding entities capable
of recognizing inaccessible epitopes. Their ability to penetrate tissues and cross the blood-brain barrier makes
them well-suited for treating viral infections that affect the Central Nervous System (CNS). This project focuses
on addressing Henipaviruses (HNV) and arenaviruses (ARV), which pose significant global health risks but
lack specific treatments. HNVs can cause severe respiratory and Central Nervous System (CNS) illnesses with
high mortality rates. On the other hand, ARV infections are responsible for fatal hemorrhagic fever. Specifically,
the study targets Nipah virus (NiV) and Hendra virus (HeV) as prototypes for HNV, as well as Lassa virus
(LASV) and Machupo virus (MACV) for ARV. The research aims to develop nanobody-based therapeutic
approaches by targeting the viral entry machinery, such as the glycoproteins G and F for HNV and the
glycoprotein complex (GPC) for ARV. The project utilizes three nanobody development platforms, including
camelid animals, nanomice and human nanobody libraries, to efficiently identify potential nanobody leads. By
employing a structure-based approach, the project aims to understand viral neutralization mechanisms,
improve nanobody engineering techniques, and design nanobodies capable of effectively penetrating the
blood-brain barrier. The specific objectives involve identifying cross-reactive nanobodies for HNVs, developing
nanobodies to overcome the glycan shield of ARVs, conducting structural characterization, enhancing
nanobody efficacy and CNS bioavailability, and expanding the research to include other viral targets within the
HNV and ARV groups in the second phase. Ultimately, the project aims to contribute to the development of
effective nanobody-based therapies for HNV and ARV infections, while establishing a generalizable strategy
for future emerging viruses with similar characteristics, thereby mitigating the global public health risks
associated with these pathogens.

## Key facts

- **NIH application ID:** 10862506
- **Project number:** 1U19AI181930-01
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Jianliang Xu
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $4,640,497
- **Award type:** 1
- **Project period:** 2024-07-30 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862506

## Citation

> US National Institutes of Health, RePORTER application 10862506, RP5: Nanobody therapeutics against henipaviruses, arenaviruses, and structural characterization (1U19AI181930-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10862506. Licensed CC0.

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