# Inhibition of SARS-CoV-2 infection with a pan-coronavirus anti-viral peptide

> **NIH NIH R43** · SAPIENCE THERAPEUTICS, INC. · 2022 · $288,178

## Abstract

ABSTRACT
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is a serious threat to global public health,
necessitating the rapid development of safe and effective medical countermeasures. SARS-CoV-2 pathogenicity
requires a series of protein-protein interactions (PPI) involving the virus’ S protein that leads to virus attachment
and fusion. Initially, the receptor binding domain (RBD) on the S protein S1 subunit binds to ACE2 receptors on
the host cell. This triggers a conformational change in the S protein S2 subunit, driving the viral heptad repeat 1
(HR1) and heptad repeat 2 (HR2) domains of S2 to form a six-helical bundle (6-HB), enabling the viral envelope
to be brought in close proximity to the host membrane, thus promoting viral fusion. Peptides have emerged
recently as a therapeutic class capable of targeting and disrupting PPI with high affinity and specificity. We
hypothesize antagonism of the virus S protein with a peptide therapeutic will provide an effective anti-viral
strategy for SARS-CoV-2 infection, and potentially a pan-coronavirus intervention. We propose a plan to select
a lead candidate peptide antagonist based upon target binding and viral neutralization in vitro, with consideration
of escape mutants, and attenuation of virus load and shedding in a ferret challenge model in vivo. Successful
completion of this program will support advancement of the lead candidate peptide to IND-enabling studies, and
provide the rationale for submission of a Phase II SBIR proposal to evaluate inhalation delivery for severe
respiratory disease.

## Key facts

- **NIH application ID:** 10401492
- **Project number:** 5R43AI157521-02
- **Recipient organization:** SAPIENCE THERAPEUTICS, INC.
- **Principal Investigator:** Jim Rotolo
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $288,178
- **Award type:** 5
- **Project period:** 2021-05-04 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401492

## Citation

> US National Institutes of Health, RePORTER application 10401492, Inhibition of SARS-CoV-2 infection with a pan-coronavirus anti-viral peptide (5R43AI157521-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10401492. Licensed CC0.

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