Development of a Novel Drug Candidate, CSP7, for the Treatment of COVID-19
Abstract
FY20 PRMRP Topic Areas: Emerging Viral Diseases and Respiratory Health. In the late 2019, several unidentified pneumonia cases were found in Wuhan, China, which rapidly spread to all around the world due to a newly identified coronavirus, SARS-CoV-2 (CoV2). Corona virus disease 2019 (COVID-19) is highly infectious and lethal, in part because of induction of a systemic inflammatory cytokine storm that may induce acute lung injury (ALI) and its more severe clinical form called acute respiratory distress syndrome (ARDS). Patients with ALI or ARDS often die due to acute lung inflammation, accelerated pulmonary organization with diffuse alveolar damage (DAD), and multiple organ failure. Currently, there is no cure for CoV2-induced ALI, which afflicts millions of patients in the US and worldwide. Elevated levels of airway and type II alveolar epithelial cell (AEC) death with increased lung inflammation were found in mice models of ALI such as ALI due to sepsis or and/or influenza A virus (A) infection with or without cigarette smoke exposure, or ALI with accelerated fibrosis due to bleomycin and transforming growth factor beta. In addition, increased expression of Caveolin-1 (Cav1)-mediated tumor suppressor protein, p53, in these models was found to induce AEC apoptosis and pulmonary inflammation. Further, mice deficient in Cav1 or p53 expression resisted AEC apoptosis and lung injury. These studies collectively highlight the central role of Cav1 in the pathogenesis of ALI and support the potential of targeting increased Cav1 in AECs to mitigate lung dysfunction associated with CoV2 infection. We will test a novel therapeutic candidate; CSP7 (a 7- mer fragment of Cav1 scaffolding domain peptide) to protect against severe ALI and mortality associated with COVID-19.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110095
Entities
People
- Sreerama Shetty
Organizations
- United States Army
- University of Texas Health Science Center at Tyler