Structural Evaluation of the Spike Glycoprotein Variants on SARS-CoV-2 Transmission and Immune Evasion

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.

Identification of potent small molecule inhibitors of SARS-CoV-2 entry

“…Delta, or B.1.617.2, is now circulating in 98% of the countries worldwide and is considerably more transmissible (∼2 fold) than the first Wuhan strain. It has ∼10 mutations in the S glycoprotein, with the four of them associated to higher virulence (L452R, T478K, D614G and P681R [41] ). These may support the increase in vaccine breakthrough recently observed with this variant.…”

Identification of Potent Small Molecule Inhibitors of SARS-CoV-2 Entry

“…Delta, or B.1.617.2, is now circulating in 98% of the countries world wide and is considerably more transmissible (~2 fold) than the first Wuhan strain. It has ~10 mutations in the S glycoprotein, with the four of them associated to higher virulence (L452R, T478K, D614G and P681R 55 ). These may support the increase in vaccine breakthrough recently observed with this variant.…”

SARS-CoV-2 variants and effectiveness of vaccines: a review of current evidence

“…The p.S13I and p.W152C completely diminish the activity of monoclonal NTD-specific antibodies. 56 Although the two Delta mutations were associated with high virus levels and transmissibility, strong binding to human receptors and severe clinical manifestations, 57,58 they were not enough to categorize the Epsilon variant as VOC.…”