Spike conformation transition in SARS-CoV-2 infection

Luo, Liaofu; Zuo, Yongchun

A theory on the conformation transition for SARS-CoV-2 spike protein (S) is established. The conformation equilibrium between open (up) and closed (down) conformations of receptor binding domain (RBD) is studied from the first-principle. The free energy change in conformation transition of S protein is introduced and we demonstrated that it includes two parts, one from the difference of conformation potential and another from the variation of structural elasticity. The latter is dependent of amino acid mutation. When the amino acid mutation of S protein causes a substantial reduction of elastic energy the equilibrium is biased to the open conformation. Only then can the virus infection process continue. That both the D614G mutation and the K986P mutation increase the COVID-19 infectivity and why a large number of mutations, including those at interface residues, have not been selected in current SARS-CoV-2 pandemic are interpreted from the presented theory. The evolution of coronavirus dependent on the alteration of conformation equilibrium is indicated. Finally, introduction of electric field to change the conformation potential barrier and how the conformation equilibrium depends on temperature and humidity are briefly discussed.