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The SARS-CoV-2 virus has shown the ability to frequently mutate resulting in several notable variants. Several of these variants that appear to be more infectious have been classified as variants of concern. While these variants of concern contain multiple mutations across the SARS-CoV-2 RNA genome, structural mutations within the Spike protein are of great interest. These mutations may alter SARS-CoV-2 infectivity and transmissibility, and potentially affect vaccine and therapeutic efficacy. Highlighted here are the most important variants to date.

Image of SARS-CoV-2 Spike protein map with domains showing mutations specific to each coronavirus variant

Coronavirus Variants of Concern

Alpha Variant B.1.1.7 (UK)

Emerged in the United Kingdom in December 2020. This lineage has been found to be 50% more infectious and slightly more deadly than other SARS-CoV-2 strains. B.1.1.7 has now been detected in over 90 countries. In the United States, it has become the dominant lineage and has been detected in all 50 states.

Key Spike protein mutations
  • N501Y, results in increased binding to ACE-2
  • P681H, mutation occurs near the furin cleavage site needed for membrane fusion, potentially impact viral infectivity.
  • H69-V70 deletion, results in a conformational change of unknown significance
  • Other Spike protein mutations: Y144del, A570D, D614G, T716I, S982A, D1118H

Beta Variant B.1.351 (South Africa)

First identified in South Africa in December 2020, it has now reached at least 48 countries and was detected in the United States in January, and today has spread to at least 25 states. Vaccines against SARS-CoV-2 have shown reduced protection against B.1.351 than other variants.

Key Spike protein mutations
  • N501Y, results in increased binding to ACE-2
  • K417N, results in increased binding to ACE-2
  • E484K, decreases some antibodies’ ability to recognize the spike protein and may reduce vaccine efficacy. This mutation has also been found in some B.1.1.7 variants.
  • Other Spike protein mutations: L18F, D80A, D215G, D614G, A701V

Gamma Variant P.1 (Brazil)

First detected in Japan in four travelers from Brazil in December 2020. The lineage was traced back to Manaus, Brazil. It is now the predominant variant in Manaus and several other South American cities and has spread to over 42 countries. In the United States, 31 states have confirmed P.1 variant cases.

Key Spike protein mutations
  • N501Y, also found in B.1.1.7 and B.1.351, results in increased binding to ACE-2
  • K417T, same amino acid position as the K417N mutation in B.1.351, likely affects ACE-2 binding
  • E484K, also found in B.1.351, may reduce antibody binding
  • E484K, also found in B.1.351, may reduce antibody binding

Delta Variant B.1.617.2 (India)

First identified in Maharashtra, India in October 2020, this variant has spread globally and is partially responsible for the large rise in COVID-19 cases and deaths in India this year. The Delta variant is one of three sublineages of B.1.617, designated B.1.617.2. It contains two mutations in the receptor binding domain of the Spike protein, T478K and L452R. The other two sublineages, B.1.617.1 (Kappa) and .3 share the same L452R mutation as the Delta variant but have an E484Q mutation instead of T478K. Data from several sources report that vaccines against SARS-CoV-2 and convalescent sera offer reduced but sufficient protection against the B.1.617 variants.

Key Spike protein mutations

  • E484Q, this mutation is at the same position as the E484K mutation found in the South African and Brazilian variants and is thought to exhibit similar effects as the E484K.
  • L452R, disrupts a hydrophobic interaction on the Spike RBD surface potentially affecting antibody neutralization and ACE-2 binding.
  • T478K, present in the Delta variant, sublineage B.1.617.2
India Variant Map 525x315
Image of SARS-CoV-2 Spike protein map with domains showing mutations specific to each coronavirus variant

Spike Protein Mutations that may affect coronavirus transmission

The D614G mutation emerged early in the COVID-19 pandemic and quickly became the dominant strain in many parts of the world. The mutation which resides in the carboxy end of the S1 subunit of the spike protein is responsible for enhanced infectivity compared to the original strain leading to much higher viral transmission. However, it does not appear to affect severity of COVID-19 disease. The D614G mutation is so widespread globally and therefore found in other variants. For simplicity, it is not listed in other variants on this page.

The N501Y mutation occurred independently in multiple variants of concern including the U.K., South African, and Brazilian variants. The mutation resides within the receptor binding domain (RBD) of the Spike protein near the tip and increases binding affinity to human ACE-2. N501Y is currently being studied to determine its effect on disease transmission, antibody recognition, and vaccine efficacy.

The E484K mutation occurred independently in multiple variants of concern including the South African and Brazilian variants. And it has been found in several samples of the U.K. variant. The mutation resides within the receptor binding domain (RBD) of the Spike protein on the outside face of the protein slightly altering its conformation. This mutation has been shown to help the virus evade detection by antibodies and impact vaccine efficacy.

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