# Structural Dynamics of Viral Proteins: Computational Investigation of Capsids, Lytic Peptides and Nucleoproteins Under Varying Conditions

> **NIH NIH R35** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $385,900

## Abstract

This project presents a multiscale computational investigation into stages of the infection process for two
classes of viruses. We will study non-enveloped viruses to understand the mechanisms of membrane
disruption by this class of virus. The ability of viruses to transport across membranes is essential for infection,
yet for non-enveloped viruses the membrane disruption/transport mechanisms are poorly characterized. Non-
enveloped viruses include many public health threats such as hepatitis A, hepatitis E, rotavirus, coxsackie B
and rhinoviruses, which infect millions of people annually. The studies in the proposal will focus on two model
system viruses, which infect insects, but the knowledge gained in these studies should be transferrable to
human infecting non-enveloped viruses. Specifically, this proposal is concerned with understanding how lytic
peptides are externalized from the interior of non-enveloped virus capsids and how the process is regulated by
pH. Additionally, this study will focus on the interactions of the lytic peptides once they have been externalized
from the capsid. These interactions include membrane binding, membrane insertion, peptide oligomerization
and modulation of membrane mechanical properties. Significant findings from these studies will include
detailed structural and energetic information regarding these infection related processes, which will be valuable
in the development of anti-viral therapies against non-enveloped viruses. The second class of virus under
study in this proposal are Arenaviruses, and specifically Lassa virus. Lassa virus causes hemorrhagic fevers in
infected individuals and has high mortality rates. NIH classifies Lassa as a Category A Priority Pathogen
because of the high risk it poses to public health and national security. This proposal is concerned with
understanding the mechanisms of recognition of viral RNA by the Lassa nucleoprotein and the formation of the
ribonucleoprotein complex, which is essential for viral replication and transcription. Characterizing the strength
and nature of these interactions will provide the mechanistic basis for development of novel antiviral strategies
targeted against Lassa. In all aspects of this proposal we will employ multiscale modeling methods and novel
experimental data will be integrated with the computational studies through multiple experimental
collaborations.

## Key facts

- **NIH application ID:** 9932378
- **Project number:** 5R35GM119762-05
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Eric Robert May
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,900
- **Award type:** 5
- **Project period:** 2016-07-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932378

## Citation

> US National Institutes of Health, RePORTER application 9932378, Structural Dynamics of Viral Proteins: Computational Investigation of Capsids, Lytic Peptides and Nucleoproteins Under Varying Conditions (5R35GM119762-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932378. Licensed CC0.

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