# Structure and Regulation of The Respiratory Syncytial Virus Polymerase

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $69,438

## Abstract

PROJECT ABSTRACT
Non-segmented negative-sense (NNS) RNA viruses include many of our most pathogenic and sometimes deadly
viruses, such as measles, rabies, Ebola, and respiratory syncytial virus (RSV). Unfortunately, no effective
vaccine or antiviral therapy is available to prevent or treat infection by RSV and many other NNS RNA viruses.
Therefore, there is a critical need to define the structural and molecular basis of RNA synthesis of NNS RNA
viruses and any differences between them. Our long-term goal is to understand the RNA synthesis machinery
of NNS RNA viruses and facilitate the development of antiviral drugs. Our overall objectives in this application
are to elucidate the molecular mechanisms of the RSV polymerase and provide functional and structural insights
into RSV RNA synthesis. Our underlying hypothesis is that the catalytic activities of RNA polymerization, cap
addition, and cap methylation reside within the RSV L protein, and L requires a dynamic assembly with its
cofactors P and M2-1 to coordinate these activities during RNA synthesis. The rationale for this project is that
understanding the mechanism of the RSV RNA synthesis is likely to offer robust scientific frameworks whereby
new strategies to investigate related NNS RNA viruses can be developed. To test the central hypothesis, we will
define the functional organization of the RSV L protein and determine the structure of the RSV polymerase using
cryo-EM. We will also define the regulatory mechanisms of the RSV transcription by M2-1. These results are
expected to have a broader impact beyond RSV because the shared strategies of RNA synthesis machines
among NNS RNA viruses imply that our findings will be relevant to all members of this order. This proposed
research program is innovative, in the applicant’s opinion, because the proposed research will lay solid
foundations for in-depth mechanistic studies of the novel enzymatic activities of NNS RNA viruses, and define
novel structural and biochemical features of the RSV L protein as well as provide novel insights on the regulation
of RSV RNA synthesis. The proposed research is significant because it leverages the power of interdisciplinary
approaches that include single-particle cryo-EM to open new horizons for visualizing key stages of RSV RNA
synthesis effectively. Ultimately, such knowledge has the potential of offering new opportunities for the rational
design of novel antiviral drugs to treat the devastating diseases that RSV and related NNS RNA viruses cause.

## Key facts

- **NIH application ID:** 10135451
- **Project number:** 3R01GM130950-02S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Bo Liang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $69,438
- **Award type:** 3
- **Project period:** 2019-09-20 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135451

## Citation

> US National Institutes of Health, RePORTER application 10135451, Structure and Regulation of The Respiratory Syncytial Virus Polymerase (3R01GM130950-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135451. Licensed CC0.

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