Introduction: Similarly, the E484K and K417N/T mutations in the RBD that were first described in the B.1.351 and P.1 lineages likely due to immune evasion from vaccine or natural infection-elicited antibodies, are now present in several other lineages.

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Result: Although both K417N and K417T presented a modest increase in the on-rate kinetic by ~1.56 and ~1.11 folds, the accelerated off-rate kinetics dictated the overall decrease affinity of these mutants.

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Result: Interestingly, three mutations/deletion in this VOC decreased the interaction with ACE2-Fc, namely R246I and Delta242-244 in the NTD, as well as K417N in the RBD.

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Result: In addition to the 29 convergent mutations that displayed frequency increases between March 15 and June 1, 2021, the meta-signature includes deletion mutations at ORF1a/3675-3677, S/69-70, S/144, and S/241-243 (which, while displaying convergence between the different 501Y lineages, were not amenable to selection analyses) and the convergent signature substitutions L18F, K417N/K, and N501Y (which were already at high frequencies in multiple 501Y lineages by March 15, 2021).

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Result: In this regard, while mutations at S/20, S/80, S/138, S/215, and S/570 in different lineages do not predominantly converge on the same encoded amino acid states, they could nevertheless still be convergent on similar fitness objectives (immune escape or compensation for the fitness costs of other mutations): such as is likely the case with the also not strictly

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