Facing the wrath of enigmatic mutations: a review on the emergence of severe acute respiratory syndrome coronavirus 2 variants amid coronavirus disease-19 pandemic

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging respiratory virus responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic. More than a year into this pandemic, the COVID-19 fatigue is still escalating and takes hold of the entire world population. Driven by the ongoing geographical expansion and upcoming mutations, the COVID-19 pandemic has taken a new shape in the form of emerging SARS-CoV-2 variants. These mutations in the viral spike (S) protein enhance the virulence of SARS-CoV-2 variants by improving viral infectivity, transmissibility and immune evasion abilities. Such variants have resulted in cluster outbreaks and fresh infection waves in various parts of the world with increased disease severity and poor clinical outcomes. Hence, the variants of SARS-CoV-2 pose a threat to human health and public safety. This review enlists the most recent updates regarding the presently characterized variants of SARS-CoV-2 recognized by the global regulatory health authorities (WHO, CDC). Based on the slender literature on SARS-CoV-2 variants, we collate information on the biological implications of these mutations on virus pathology. We also shed light on the efficacy of therapeutics and COVID-19 vaccines against the emerging SARS-CoV-2 variants.

Fig. 1

Timeline of key events unfolding the emergence of SARS‐CoV‐2 variants during the COVID‐19 pandemic. The first confirmed cases of SARS‐CoV‐2 were reported in December 2019 in Wuhan, China. Following confirmation of human‐to‐human transmission and its global dissemination, the WHO announced COVID‐19 as a pandemic. In the successive 12 months, hundreds of SARS‐CoV‐2 variants have emerged, out of which four have been designated as variant of concern (VOC) and seven as variant of interest (VOI) by the WHO. Five COVID‐19 vaccines have also been approved for emergency use authorization (EUA) by the WHO. Since then, more than 180 million cases of SARS‐CoV‐2 have been confirmed, with nearly 3.9 million deaths worldwide.

Fig. 2

World map depicting the geographical distribution of SARS‐CoV‐2 variants (VOI and VOC) till 29th May 2021. The epicentre of the COVID‐19 pandemic (Wuhan, China) has been shown in a red marking. The VOI and VOC have been listed alongside the countries they were first reported in with green and violet colours respectively. The pie charts depict the relative frequencies of SARS‐CoV‐2 VOC in different countries where the variants originated. The variants are colour‐coded as follows B.1.1.7 (), B.1.351 (), B.1.617 (), P.1 () and others (). Others represent VOI. Source: https://covariants.org/.

Fig. 3

A simplified phylogenetic tree illustrating the diversity of SARS‐CoV‐2 variants concerning the S protein. The variants diverge from their ancestral root (Wuhan), accumulating mutations in the S protein as they spread globally. The boxes represent various lineages of the SARS‐CoV‐2 variants, and the branches indicate the inferred month of emergence of different variants. VOC and VOI are shown in orange and blue boxes respectively.

Fig. 4

Mechanistic insight into the biological implications of the mutations reported in SARS‐CoV‐2 VOC and VOI. Individual or a combination of mutations in the spike (S) protein drives the virulence attributes of SARS‐CoV‐2 variants. Amino acid substitutions in the S protein have been shown to boost viral infectivity by enhancing binding to the hACE2 receptor. Mutations increase the immune evasion abilities of SARS‐CoV‐2 variants by evading antibodies and protective immune responses generated from previous viral infection and vaccination. SARS‐CoV‐2 variants also exhibit increased transmissibility leading to fresh cluster outbreaks and community transmission.