Specifically, the energy contribution of K493 in RBDOmicron decreased about 1.90 kcal/mol to Q493 in RBDWT, and the energy contribution of R498 in RBDOmicron decreased about 4.15 kcal/mol to Q498 in RBDWT. As shown in Figure , Q493 in RBDWT could form tight interactions with K31 and E35 in ACE2. By calculating distances of K31ACE2-Q493RBD and K31ACE2-K493RBD (Figure ), we found that K31ACE2 moves away from K493RBD, which may be due to the repulsion of lysine with the same electrical properties. As shown in Figure , K353ACE2 also moves away from R498RBD. Hence, we speculate that the repulsion between positively charged residues is the main cause of the decreased binding free energy in ACE2-RBDOmicron. Differently, K493RBD forms a tighter interaction with E35ACE2 (Figure ), which partly compensates for the effect of positively charge repulsion. While the lack of compensation effect in R493RBD (Figure &5B) leads to its severe decreased interations with ACE2.