Evolution, Mode of Transmission, and Mutational Landscape of Newly Emerging SARS-CoV-2 Variants

Abstract

The recent emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a significant concern for public health worldwide. New variants have been classified either as variants of concern (VOCs) or variants of interest (VOIs) by the CDC (USA) and WHO. The VOCs include lineages such as B.1.1.7 (20I/501Y.V1 variant), P.1 (20J/501Y.V3 variant), B.1.351 (20H/501Y.V2 variant), and B.1.617.2. In contrast, the VOI category includes B.1.525, B.1.526, P.2, and B.1.427/B.1.429. The WHO provided the alert for last two variants (P.2 and B.1.427/B.1.429) and labeled them for further monitoring. As per the WHO, these variants can be reclassified due to their status at a particular time. At the same time, the CDC (USA) has marked these two variants as VOIs up through today. This article analyzes the evolutionary patterns of all these emerging variants, as well as their geographical distributions and transmission patterns, including the circulating frequency, entropy diversity, and mutational event diversity throughout the genomes of all SARS-CoV-2 lineages. The transmission pattern was observed highest in the B.1.1.7 lineage. Our frequency evaluation found that this lineage achieved 100% frequency in early October 2020. We also critically evaluated the above emerging variants mutational landscape and significant spike protein mutations (E484K, K417T/N, N501Y, and D614G) impacting public health. Finally, the effectiveness of vaccines against newly SARS-CoV-2 variants was also analyzed. IMPORTANCE Irrespective of the aggressive vaccination drive, the newly emerging multiple SARS-CoV-2 variants are causing havoc in several countries. As per the CDC (USA) and WHO, the VOCs include the B.1.1.7, P.1, B.1.351, and B.1.617.2 lineages, while the VOIs include the B.1.525, B.1.526, P.2, and B.1.427/B.1.429 lineages. This study analyzed the evolutionary patterns, geographical distributions and transmission patterns, circulating frequency, entropy diversity, and mutational event diversity throughout the genome of significant SARS-CoV-2 lineages. A higher transmission pattern was observed for the B.1.1.7 variant. The study also evaluated the mutational landscape and important spike protein mutations (E484K, K417T/N, N501Y, and D614G) of all of the above variants. Finally, a survey was performed on the efficacy of vaccines against these variants from the previously published literature. The results presented in this article will help design future countrywide pandemic planning strategies for the emerging variants, next-generation vaccine development using alternative wild-type antigens and significant viral antigens, and immediate planning for ongoing vaccination programs worldwide.

Keywords: effect on vaccines; emerging variants; mutational landscape; transmission pattern.

FIG 1

Flowchart showing the methodology of our study.

FIG 2

Phylogenetic tree of all circulating lineages of newly SARS-CoV-2 variants between December 2019 and June 2021. The phylogenetic tree of all circulating lineages was developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 3

Phylogenetic trees of significant VOCs between December 2019 and June 2021. (A) Phylogenetic tree highlighting lineage B.1.1.7 (Alpha) and showing the relationship with other circulating lineages. (B) Phylogenetic tree highlighting lineage P.1 (Gamma) and showing the relationship with different circulating lineages. (C) Phylogenetic tree highlighting lineage B.1.351 (Beta) and showing the relationship with other circulating lineages. (D) Phylogenetic tree showing lineage B.1.617.2 (Delta) and showing the relationship with different circulating lineages. The phylogenetic trees of significant VOCs were developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 4

Phylogenetic trees of significant VOIs between December 2019 and June 2021. (A) Phylogenetic tree highlighting lineage B.1.525 (Eta) and showing the relationship with other circulating lineages. (B) Phylogenetic tree highlighting lineage B.1.526 (Iota) and showing the relationship with different circulating lineages. (C) Phylogenetic tree highlighting lineage P.2 (Zeta) and showing the relationship with other circulating lineages. (D) Phylogenetic tree highlighting lineage B.1.427/B.1.429 (Epsilon) and showing the relationship with other circulating lineages. The phylogenetic trees of significant VOIs were developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 5

Scatterplot showing the genome diversity cluster of all circulating lineages between December 2019 and June 2021. The scatterplot of all circulating lineages was developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 6

Scatterplots showing the genome diversity clusters of significant VOCs between December 2019 and June 2021. (A) Scatterplot showing the genome samples of lineage B.1.1.7 (Alpha) with a linear regression line. (B) Scatterplot showing the genome samples of lineage P.1 (Gamma) with a linear regression line. (C) Scatterplot showing the genome samples of lineage B.1.351 (Beta) with a linear regression line (D) Scatterplot showing the genome samples of lineage B.1.617.2 (Delta) with a linear regression line. The scatterplots of significant VOCs were developed before 27 June 2021 through the Nextstrain server, which is using GISAID data.

FIG 7

Scatterplots showing the genome diversity cluster of significant VOIs between December 2019 and June 2021. (A) Scatterplot showing the genome samples of the lineage B.1.525 (Eta) with a linear regression line. (B) Scatterplot showing the genome samples of the lineage B.1.526 (Iota) with a linear regression line. (C) Scatterplot showing the genome samples of the lineage P.2 (Zeta) with a linear regression line. (D) Scatterplot showing the genome samples of the lineage B.1.427/B.1.429 (Epsilon) with a linear regression line. The scatterplots of significant VOIs were developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 8

Geographical distribution and transmission pattern from the source to other countries of all circulating lineages between December 2019 and June 2021. The geographical distribution and transmission pattern of all circulating lineages were developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 9

Geographical distributions and transmission patterns from the source to other countries of significant VOCs between December 2019 and June 2021. (A) Geographical distribution and transmission pattern of the B.1.1.7 (Alpha) lineage. (B) Geographical distribution and transmission pattern of the P.1 (Gamma) lineage. (C) Geographical distribution and transmission pattern of the B.1.351 (Beta) lineage. (D) Geographical distribution and transmission pattern of the B.1.617.2 (Delta) lineage. The geographical distributions and transmission patterns of all circulating lineages were developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 10

Geographical distributions and transmission patterns from the source to other countries of significant VOIs between December 2019 and June 2021. (A) Geographical distribution and transmission pattern of the B.1.525 (Eta) lineage. (B) Geographical distribution and transmission pattern of the B.1.526 (Iota) lineage. (C) Geographical distribution and transmission pattern of the P.2 (Zeta) lineage. (D) Geographical distribution and transmission pattern of the B.1.427/B.1.429 (Epsilon) lineage. The geographical distributions and transmission patterns of all circulating lineages were developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 11

Frequency pattern of all circulating lineages between December 2019 and June 2021. The frequency pattern of all circulating lineages was developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 12

Frequency patterns of significant VOCs between December 2019 and June 2021. (A) Frequency pattern of the B.1.1.7 (Alpha) lineage. (B) Frequency pattern of the P.1 (Gamma) lineage. (C) Frequency pattern of the B.1.351 (Beta) lineage. (D) Frequency pattern of the B.1.617.2 (Delta) lineage. The frequency patterns of significant VOCs were developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 13

Frequency patterns of significant VOIs between December 2019 and June 2021. (A) Frequency pattern of the B.1.525 (Eta) lineage. (B) Frequency pattern of the B.1.526 (Iota) lineage. (C) Frequency pattern of the P.2 (Zeta) lineage. (D) Frequency pattern of the B.1.427/B.1.429 (Epsilon) lineage. The frequency patterns of significant VOIs were developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 14

Entropy diversity and event diversity of all circulating lineages between December 2019 and June 2021. The entropy diversity and event diversity of all circulating lineages were developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 15

Entropy diversities and event diversities of significant VOCs between December 2019 and June 2021. (A) Entropy diversity and event diversity of the B.1.1.7 (Alpha) lineage. (B) Entropy diversity and event diversity of the P.1 (Gamma) lineage. (C) Entropy diversity and event diversity of the B.1.351 (Beta) lineage. (D) Entropy diversity and event diversity of the B.1.617.2 (Delta) lineage. Entropy diversity and event diversity of significant VOCs were developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 16

Entropy diversity and event diversity of significant VOIs between December 2019 and June 2021. (A) Entropy diversity and event diversity of the B.1.525 (Eta) lineage. (B) Entropy diversity and event diversity of the B.1.526 (Iota) lineage. (C) Frequency pattern of the P.2 (Zeta) lineage. (D) Entropy diversity and event diversity of the B.1.427/B.1.429 (Epsilon) lineage. The entropy diversities and event diversities of significant VOIs were developed before 27 June 2021 through the Nextstrain server, using GISAID data.

FIG 17

Mutational landscapes throughout the genomes of significant VOCs between December 2019 and June 2021. (A) Significant mutational landscape throughout the genome of the B.1.1.7 (Alpha) lineage. (B) Significant mutational landscape throughout the genome of the P.1 (Gamma) lineage. (C) Significant mutational landscape throughout the genome of the B.1.351 (Beta) lineage. (D) Significant mutational landscape throughout the genome of the B.1.617.2 (Delta) lineage.

FIG 18

Mutational landscapes throughout the genomes of significant VOIs between December 2019 and June 2021. (A) Significant mutational landscape throughout the genome of the B.1.525 (Eta) lineage. (B) Significant mutational landscape throughout the genome of the B.1.526 (Iota) lineage. (C) Significant mutational landscape throughout the genome of the P.2 (Zeta) lineage. (D) Significant mutational landscape throughout the genome of the B.1.427/B.1.429 (Epsilon) lineage.

FIG 19

Significant mutational landscapes in spike protein of significant VOCs between December 2019 and June 2021. (A) Mutational landscape in the spike protein of the B.1.1.7 (Alpha) lineage (closed form). (B) Mutational landscape in the spike protein of the B.1.1.7 (Alpha) lineage (closed form with 90° rotation) (C) Mutational landscape in the spike protein of the P.1 (Gamma) lineage. (D) Mutational landscape in the spike protein of the B.1.351 (Beta) lineage. (E) Mutational landscape in the spike protein of the B.1.617.2 (Delta) lineage.

FIG 20

Significant mutational landscapes in spike protein of significant VOIs between December 2019 and June 2021. (A) Mutational landscape in the spike protein of the B.1.525 (Eta) lineage. (B) Mutational landscape in the spike protein of the B.1.526 (Iota) lineage. (C) Mutational landscape in spike protein of the P.2 (Zeta) lineage. (D) Mutational landscape in the spike protein of the B.1.427/B.1.429 (Epsilon) lineage.

FIG 21

Structural landscape of the E484K mutation. (A) Contacts of the wild type (Glu). (B) Interactions of the mutant type (Lys). (C) Interactions of the wild type (Glu) with the mutant (Lys).

FIG 22

Structural landscape of the K417T mutation. (A) Contacts of the wild type (Lys). (B) Interactions of the mutant type (Thr). (C) Interactions of the wild type (Lys) with the mutant (Thr).

FIG 23

Structural landscape of the K417N mutation. (A) Contacts of the wild type (Lys). (B) Interactions of the mutant (Asn). (C) Interactions of the wild type (Lys) with the mutant (Asn).

FIG 24

Structural landscape of the N501Y mutation. (A) Contacts of the wild type (Asn). (B) Interactions of the mutant (Tyr). (C) Interactions of the wild type (Asn) with the mutant (Tyr).

FIG 25

Structural landscape of the D614G mutation. (A) Contacts of the wild type (Asp). (B) Interactions of the mutant (Gly). (C) Interactions of the wild type (Asp) with the mutant (Gly).