Instead of focusing on targeting viral RBD sequences that are subject to continual mutation, an alternative approach like an ACE2-IgM trap could provide a durable therapeutic solution for addressing the challenge of Omicron virus evolution that has continued for over two years, and other CoVs dependent on ACE2 as a major receptor for infection, which include alpha CoV that could cause lethal infection in certain populations, and animal-origin sarbecoviruses with pandemic potential. The gene discussed is CD40LG; the disease is infection.