# An antioxidant enzyme to suppress hyperinflammation induced by SARS-CoV-2

> **NIH NIH R56** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $380,317

## Abstract

PROJECT SUMMARY
The COVID-19 pandemic has taken a significant toll on people worldwide, and current treatment is mainly
supportive. While the pathogenesis of COVID-19 remains elusive, accumulating evidence suggests that a
subgroup of patients with severe COVID-19 might have virally driven hyperinflammation and immune
dysregulation. We propose herein reactive oxygen species contribute to hyperinflammation and immune
dysregulation in severe COVID-19 patients, which can be treated by an antioxidant enzyme—catalase that
regulates cytokine production, protects against oxidative injury, and represses replication of SARS-CoV-2. This
therapeutic based on catalase, the most abundant antioxidant enzyme ubiquitously present in the liver,
erythrocytes and alveolar epithelial cells, is the most effective catalyst to breakdown hydrogen peroxide and
minimize the downstream reactive oxygen species. The potential of catalase as a therapeutic agent has been
explored for different diseases in vitro and in mouse models, including influenza-associated pneumonia,
respiratory infections caused by respiratory syncytial virus (RSV), and inflammatory disease associated with
oxidative stress. However, the efficacy of catalase has been hampered by its poor stability and short plasma
half-life. Particularly, in the context of COVID-19 patients, death of the alveolar cells and inflammation could
result in high local concentrations of proteases, further deteriorating the stability of catalase. We recently
published an effective delivery system of catalase using the nanocapsule technology. Catalase delivered by
nanocapsules assists to regulate production of cytokines and protect oxidative injury, as demonstrated in
human leukocytes and alveolar epithelial cells, and repress replication of SARS-CoV-2 in rhesus macaques,
without noticeable toxicity. In this proposal, we will further investigate the immunoregulatory effect of catalase
nanocapsules on hyperinflammation induced by SARS-CoV-2 ex vivo, further optimize their biodistribution,
pharmacokinetics, and delivery efficiency to SARS-CoV-2 infected organs, and test their therapeutic efficacy in
the SARS-CoV-2 infection mice developing respiratory disease resembling severe COVID-19. Success of this
project may provide an effective therapeutic solution for the pandemic, as well as treatment of
hyperinflammation induced by virus infection in general.

## Key facts

- **NIH application ID:** 10665424
- **Project number:** 1R56AI163386-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jing Wen
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $380,317
- **Award type:** 1
- **Project period:** 2022-08-19 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10665424

## Citation

> US National Institutes of Health, RePORTER application 10665424, An antioxidant enzyme to suppress hyperinflammation induced by SARS-CoV-2 (1R56AI163386-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10665424. Licensed CC0.

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