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D614G mutation not associated with higher mortality, but is associated with a higher viral load and affecting younger patients https://doi.org/10.1016/j.cell.2020.11.020 . D614G mutation proposed to allow increased epitope exposure and greater neutralisation, thus should not affect vaccine efficacy https://doi.org/10.1016/j.chom.2020.11.012

Additionally a N501Y mutation in the S1 has been reported. This mutation is already present in the UK SARS-CoV-2 variant (20B/501Y.V1, B1.1.7 lineage), and is associated with high higher rates of transmission through increased receptor binding https://doi.org/10.1101/2021.01.04.425316 and potentially higher viral loads https://doi.org/10.1101/2021.01.12.20249080 . However, post vaccination sera can neutralise this variant and thus current vaccines in circulation should protect against this strain https://doi.org/10.1101/2021.01.19.21249592 .

Interestingly, examination of the global effects of the N501Y mutation revealed that MHCII presentation was poorer than wild type controls. This implicates the N501Y mutation in hindering immune cell cooperation, resulting in immune escape https://doi.org/10.1101/2021.02.02.429431

and also possibly by enhancing the lysosomal trafficking of the SARS-CoV-2 spike protein https://doi.org/10.1101/2020.12.08.417022

Another mutation in the receptor binding domain of the S protein, E484K, has been found in the South African and Brazilian variants of the virus. The glutamate to lysine substitution switches the charge on the flexible loop region of the RBD resulting in the formation of novel favourable contacts https://doi.org/10.1101/2021.01.13.426558 . Early studies indicate that higher antibody titres will be required post vaccination to neutralise the variant https://doi.org/10.1101/2021.01.26.21250543

Indeed, a recent study indicates that diversity of ACE2 expression amongst those of different ethnicities impacts selection pressures for mutations in SARS-CoV-2, for example, the D614G mutation has become dominant in North America, Europe and Africa where ACE2 expression amongst the population is low in comparison with those from China, where D614G is not the dominant form https://doi.org/10.3390/genes12010016

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