During infection, the virus first binds to a cellular receptor on host cells via the RBD region of the S1 subunit to form an RBD/receptor complex, which then triggers a conformational change in the S protein; thus involves a change from a pre-fusion state to an intermediate state, as well as formation of six-helix bundle (6-HB) structures, resulting in fusion between the viral and cell membranes, mediating the virus to enter host cells (Figs. 2 and 3B) [49, 52]. The gene discussed is PROS1; the disease is infection.