Endothelial Dysfunction in COVID

Since the development of vaccines, emerging SARS-CoV-2 variants with Spike mutations threaten vaccine effectiveness, emphasising the importance of alternative therapies. Few small molecules directly target the virus, making new treatments crucial. COVID-19 symptoms include cough, fever, and breathlessness, but severe cases can develop into ARDS through endothelial cell dysfunction, inflammation, and vascular damage. Comorbidities such as hypertension, diabetes, and obesity worsen outcomes due to endothelial impairment. We found SARS-CoV-2 enters lung endothelial cells lacking ACE2 via an RGD motif, using αvβ3 integrin and clathrin-mediated endocytosis. This entry remodels cell phenotype and promotes angiogenesis without viral replication. Blocking Spike/αvβ3 interaction prevents endothelial dysfunction, while vaccine-induced antibodies fail to inhibit this pathway. Our project aims to clarify these mechanisms and identify repurposed drugs to disrupt virus-host interactions, thereby improving patient outcomes and reducing costs. Additionally, it will advance endothelial dysfunction assessment tools for rapid clinical use.