Regulation of hyaluronic acid synthesis and breakdown can prevent significant damage of the lung epithelium in response to SARS-CoV-2 infection

• Published in: Physiology (Bethesda, Md.) Md.), 2023-05, Vol.38 (S1)
• Main Authors: Harriott, Noa, Calvert, Ben, Quiroz, Erik, Ryan, Amy
• Format: Article
• Language: English
• ISSN: 1548-9213; 1548-9221
• DOI: 10.1152/physiol.2023.38.S1.5732829

Abstract only COVID-19 remains an ongoing global pandemic causing significant respiratory distress and endothelial dysfunction in individuals susceptible to severe disease. Increased production of hyaluronic acid has been observed in patients with severe COVID-19, however its significance in COVID-19 pathogenesis is currently unknown. Hymecromone is a hyaluronic acid synthase inhibitor FDA approved for use in humans as a choleretic. We hypothesized that excessive production of hyaluronic acid by the airway epithelium, in response to SARS-CoV-2 infection, may increase hyaluronan fragments that augment epithelial dysfunction in COVID-19. We therefore evaluated a hyaluronic acid synthase inhibitor, hymecromone, for its potential to regulate the infection of respiratory epithelia by SARS-CoV-2. Using air-liquid interface models we evaluated the impact of SARS-CoV-2 infection on differentiated primary human airway epithelium in the BSL3 facility. At 100μg/ml hymecromone significantly inhibited the cytopathic effects of SARS-CoV-2 on airway epithelium (p