“…In this regard, VOC Beta( Ravi et al, 2021 ) and Gamma ( Montagutelli et al, 2021 ) could establish infection in wild-type mice, but with a milder infection than in human ACE2 transgenic mice ( Tarres-Freixas et al, 2021 ). Omicron, because of its ability to infect mice ( Bentley et al, 2021 , Liu et al, 2022 , Rissmann et al, 2022 , Suryawanshi et al, 2022 ), was hypothesized to emerge from partially fit jump species( Wei et al, 2021 ), and reversions after widespread circulation in humans could support such hypothesis. The F486V mutation found in BA.4/5 facilitates escape from certain Class 1 and Class 2 antibodies to the RBD but compromises the Spike affinity for the cellular receptor ACE2, but the R493Q reversion mutation restores receptor affinity, and consequently, the fitness of BA.4/5 ( Wang et al, 2022a ).…”