Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents significant social, economic and political challenges worldwide. SARS-CoV-2 has caused over 3.5 million deaths since late 2019. Mutations in the spike (S) glycoprotein are of particular concern because it harbours the domain which recognises the angiotensin-converting enzyme 2 (ACE2) receptor and is the target for neutralising antibodies. Mutations in the S protein may induce alterations in the surface spike structures, changing the conformational B-cell epitopes and leading to a potential reduction in vaccine efficacy. Here, we summarise how the more important variants of SARS-CoV-2, which include cluster 5, lineages B.1.1.7 (Alpha variant), B.1.351 (Beta), P.1 (B.1.1.28/Gamma), B.1.427/B.1.429 (Epsilon), B.1.526 (Iota) and B.1.617.2 (Delta) confer mutations in their respective spike proteins which enhance viral fitness by improving binding affinity to the ACE2 receptor and lead to an increase in infectivity and transmission. We further discuss how these spike protein mutations provide resistance against immune responses, either acquired naturally or induced by vaccination. This information will be valuable in guiding the development of vaccines and other therapeutics for protection against the ongoing coronavirus disease 2019 (COVID-19) pandemic.
Highlights
More than 168 million people have been infected worldwide with coronavirus disease2019 (COVID-19), resulting in over 3.5 million deaths
COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel positive-strand single-stranded RNA virus which is categorised in the subfamily Coronavirinae of the family Coronaviridae and the order
Upon the binding to angiotensin-converting enzyme 2 (ACE2), the receptor-binding domain (RBD) of the trimeric S glycoprotein adopts a protruding ‘up’ conformation which promotes the release of the S1 subunit and triggers a substantial structural rearrangement to fuse the viral membrane with the host cell membrane [37]
Summary
More than 168 million people have been infected worldwide with coronavirus disease. 2019 (COVID-19), resulting in over 3.5 million deaths (as of May 2021). COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel positive-strand single-stranded RNA virus which is categorised in the subfamily Coronavirinae of the family Coronaviridae and the order. Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two pathogenic, highly transmissible viruses that belong to the same family. They all have zoonotic origins and are likely to have originated in bats [3]. There is much debate on how SARS-CoV-2 came into contact with humans, whether directly from bats or indirectly via an intermediate animal host, such as Malayan pangolins [5]. There is evidence that SARS-CoV-2 is similar to a coronavirus found in horseshoe bats (Rhinolophus), with a sequence similarity of 98.7% to the partial RNA-dependent RNA polymerase (RdRp) gene of the bat coronavirus strain BtCoV/4991 and 87.9% similarity to bat coronavirus strains bat-SL-CoVZC45 and bat-SL-CoVZXC21 [6]
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