# A PTP4A3 inhibitor for SARS-CoV-2-mediated acute lung injury > **NIH NIH R43** · KEVIRX INC. · 2022 · $55,000 ## 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 overall goal of the project is to repurpose KVX-053 for use against SARS-CoV-2 infection and for future viral 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 PTP4A 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 injury in mice caused by the SARS-CoV-2 Spike 1 protein. ## Key facts - **NIH application ID:** 10540550 - **Project number:** 3R43HL158409-01A1S1 - **Recipient organization:** KEVIRX INC. - **Principal Investigator:** JOHN S. LAZO - **Activity code:** R43 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2022 - **Award amount:** $55,000 - **Award type:** 3 - **Project period:** 2021-09-20 → 2022-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10540550 ## Citation > US National Institutes of Health, RePORTER application 10540550, A PTP4A3 inhibitor for SARS-CoV-2-mediated acute lung injury (3R43HL158409-01A1S1). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10540550. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*