The COVID‐19 pandemic continues to have a threatening impact on a global scale, largely due to the emergence of newly SARS‐CoV‐2 variants. The Mu (PANGO lineage B.1.621), was first identified in Colombia in January 2021 and was classified as a variant of interest (VOI) in August 2021, due to a constellation of mutations that likely‐mediate an unexpectedly enhanced immune resistance to inactivated vaccineelicited antibodies. Despite recent studies suggesting that the Mu variant appears to have less infectivity than the Delta variant, here we examined the structural effect of the Mu spike protein mutations and predicted the potential impact on infectivity of the Mu variant compared with the Delta and Delta plus spike protein.