# A PTP4A3 inhibitor for SARS-CoV-2-mediated acute lung injury

> **NIH NIH R43** · KEVIRX INC. · 2022 · $6,500

## Abstract

The Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) is responsible for the current COVID-19
pandemic. SAR-CoV-2, like other coronaviruses, infects human airways and enters cells via its S (Spike) protein,
which binds to the human angiotensin-converting enzyme 2 (ACE2) and is primed by the host serine protease
TMPRSS2. Both ACE2 and TMPRSS2 have been observed on pulmonary microvascular epithelium and
endothelium. A subset of COVID-19 patients develop acute respiratory distress syndrome (ARDS) and
subsequently septic shock and multi-organ failure; about half will die. The clinical worsening in the later phases
of COVID-19 are thought to result from Spike protein binding to the pulmonary microvascular endothelium and
epithelium, which leads to a damaged respiratory tract and ultimately a systemic inflammatory response or
cytokine storm. There are currently no FDA-approved drugs/therapeutics that treat the pulmonary damage and
ARDS associated with COVID-19. KeViRx is proposing to develop an entirely new therapeutic strategy that
prevents or mitigates the initial pulmonary damage and halts the lethal cytokine storm.
 Our lead compound, KVX-053, is a reversible, selective, allosteric inhibitor of PTP4A3 phosphatase with
excellent in vivo pharmacokinetic properties and drug-like properties. Moreover, mice tolerated multiple
exposures to KVX-053 In culture KVX-053 was not cytotoxic to human ovarian epithelial cells or fibroblasts at
concentrations up to 25 µM. Surprisingly, we found that KVX-053 markedly enhanced the pulmonary
microvascular barrier function before and after injury caused by bacterial lipopolysaccharide and vascular
endothelial growth factor. PTP4A3 phosphatase is known to be induced in lung cells 12 h after SARS-CoV
infection and to control cytokine release. The overall hypothesis of this Phase I SBIR application is that the
PTP4A phosphatase family has a sentinel role in the acute lung injury of ARDS and the systemic inflammatory
response in COVID-19.The goal of the project is to repurpose KVX-053 for use in individuals with COVID-19 and
for future pandemics involving acute lung injury. This Phase I SBIR application has three proof-of-concept
Specific Tasks. Specific Task 1 will determine the ability of a novel, potent, allosteric, small molecule PTP4A3
inhibitor, KVX-053, to block SARS-CoV-2 Spike 1 protein-mediated loss of pulmonary endothelial barrier function
and cytokine release in vitro. Specific Task 2 will determine the ability of KVX-053 to block SARS-CoV-2 Spike
1 protein-mediated pulmonary alveolar epithelial barrier function and cytokine release in vitro. Specific Task 3
will determine the ability of KVX-053 to inhibit acute lung injruy in mice caused by the SARS-CoV-2 Spike 1
protein.

## Key facts

- **NIH application ID:** 10632154
- **Project number:** 3R43HL158409-01A1S2
- **Recipient organization:** KEVIRX INC.
- **Principal Investigator:** JOHN S. LAZO
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $6,500
- **Award type:** 3
- **Project period:** 2022-07-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10632154

## Citation

> US National Institutes of Health, RePORTER application 10632154, A PTP4A3 inhibitor for SARS-CoV-2-mediated acute lung injury (3R43HL158409-01A1S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10632154. Licensed CC0.

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