Annexin A5 as a treatment for COVID-19

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a novel coronavirus, SARS-CoV-2. The virus enters the host airway epithelial cells through its spike protein interaction with the host cell receptor angiotensin converting enzyme 2 (ACE2). In severe cases, the disease is complicated by acute respiratory distress syndrome (ARDS), sepsis, septic shock, and multi-organ failure, including the lungs, heart, and kidneys. While vaccines have been shown to be effective in reducing the number of cases with COVID-19, the disease is not likely to be eliminated due to the emergence of SARS-CoV-2 variants that may evade immunity to the vaccines or previous infection. It is therefore vital to develop new and effective therapies. Annexin A5 (Anx5) is a human endogenous protein with potent anti-inflammatory, anti-apoptotic and anti-coagulant properties. Our preliminary data show that Anx5 inhibits SARS-CoV-2 spike protein interactions with ACE2 and reduces cellular infection. The proposed research will examine the effects of recombinant human Anx5 on viral infection, inflammation, pulmonary and cardiovascular injuries induced by wildtype (WT) and variant SARS-CoV-2 in hamsters with and without hypertension, and tease out the precise structural basis for Anx5-mediated inhibition of Spike protein binding to ACE2. The proposed research will develop a novel clinically relevant hamster model and life-saving treatment for COVID-19.