J Korean Med Sci.  2021 May;36(18):e124. 10.3346/jkms.2021.36.e124.

Will Mutations in the Spike Protein of SARS-CoV-2 Lead to the Failure of COVID-19 Vaccines?

• Jia Z
• Gong W

• KMID: 2515857
• DOI: http://doi.org/10.3346/jkms.2021.36.e124

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has spread worldwide since it was first identified in Wuhan, China, at the end of 2019. With the global transmission of the virus, a large number of SARS-CoV-2 variants have also appeared, especially, emerging strains that have recently been discovered in the United Kingdom (variant 20I/501Y.V1, lineage B.1.1.7), South Africa (variant 20H/501Y.V2, lineage B.1.351), and Brazil (variant 20 J/501Y.V3, and lineage P.1). The common feature of these variants is that they share the N501Y mutation involving the SARS-CoV-2 spike (S) protein, which is precisely the target of most COVID-19 vaccines. Furthermore, mutations such as N501Y, E484K, and K417N in the S protein may affect viral fitness and transmissibility. However, current research on the impact of these variants on COVID-19 vaccines is still lacking. Herein, we briefly explain why most COVID-19 vaccines target the S protein, update the progress of research regarding S protein-related COVID-19 vaccines, review the latest studies concerning the effects of S protein variants on COVID-19 vaccines, and finally, propose certain strategies to deal with SARS-CoV-2 variants.

Keyword

SARS-CoV-2; COVID-19; Spike Protein; Mutation; Variant; Vaccine

Figure

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  Fig. 1 The distribution of genome-wide mutations on SARS-CoV-2 and the key mutations in S protein. The data of mutations in hCoV-19 genomes was obtained from GISAID database from January 1, 2020, to December 26, 2020. The Y-axis represents the natural logarithm frequency of each mutation in the whole genome of SARS-CoV-2. The X-axis represents the name of the marker gene or protein, and the relative positions of other unlabeled genes or proteins can be found in the GISAID database. Each mutation was shown as a solid dot colored by Open Reading Frame of hCoV-19 genome. The S protein structure was presented following a previous study9 (Wrapp et al. Science 2020;367:1260-3). The Arabic numerals below the S protein structure represent the amino acid site in the full-length amino acid sequence.SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2, S = spike, hCoV-19 = human coronavirus 2019.

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  Fig. 2 The phylogeny and mutations of SARS-CoV-2 viruses. This phylogeny shows evolutionary relationships of SARS-CoV-2 viruses from the ongoing COVID-19 pandemic (A). Although the genetic relationships among sampled viruses are quite clear, there is considerable uncertainty surrounding estimates of specific transmission dates and in the reconstruction of geographic spread. The number of mutations in hCoV-19 genomes was obtained from Nextstrain database and showed by solid dot (B). Compiled Nextstrain SARS-CoV-2 resources are available at https://nextstrain.org/sars-cov-2/. All of data was obtained on January 26, 2021.SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2, COVID-19 = coronavirus disease 2019, hCoV-19 = human coronavirus 2019.

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