The selective infection targeting CD4+ T helper cells and the high-affinity interaction between the viral spike RBD and the N-terminal domain of the CD4, assessed by molecular docking and dynamic simulations, and supported by co-immunoprecipitation and fluorescence anisotropy assays, identifies CD4 as a critical cofactor that facilitates viral attachment and promotes SARS-CoV-2 internalization in these cells (23). The gene discussed is CD4; the disease is infection.