We found that human SP-A can bind both SARS-CoV-2 S protein and hACE2 and inhibit viral entry in susceptible human lung epithelial cells in vitro; and human SP-A can attenuate lung injury and viral burden using a double humanized transgenic mouse model (expressing hACE2 and human SP-A) following SARS-CoV-2 (Delta) infection. This evidence concerns the gene SFTPA2 and infection.