SARS-CoV-2 B.1.617.2 Delta variant emergence and vaccine breakthrough

Abstract

The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and has spread throughout India, displacing the B.1.1.7 (Alpha) variant and other pre-existing lineages. Mathematical modelling indicates that the growth advantage is most likely explained by a combination of increased transmissibility and immune evasion. Indeed in vitro, the delta variant is less sensitive to neutralising antibodies in sera from recovered individuals, with higher replication efficiency as compared to the Alpha variant. In an analysis of vaccine breakthrough in over 100 healthcare workers across three centres in India, the Delta variant not only dominates vaccine-breakthrough infections with higher respiratory viral loads compared to non-delta infections (Ct value of 16.5 versus 19), but also generates greater transmission between HCW as compared to B.1.1.7 or B.1.617.1 (p=0.02). In vitro, the Delta variant shows 8 fold approximately reduced sensitivity to vaccine-elicited antibodies compared to wild type Wuhan-1 bearing D614G. Serum neutralising titres against the SARS-CoV-2 Delta variant were significantly lower in participants vaccinated with ChadOx-1 as compared to BNT162b2 (GMT 3372 versus 654, p<0001). These combined epidemiological and in vitro data indicate that the dominance of the Delta variant in India has been most likely driven by a combination of evasion of neutralising antibodies in previously infected individuals and increased virus infectivity. Whilst severe disease in fully vaccinated HCW was rare, breakthrough transmission clusters in hospitals associated with the Delta variant are concerning and indicate that infection control measures need continue in the post-vaccination era.

Modelling conformational state dynamics and its role on infection for SARS-CoV-2 Spike protein variants

“…Therefore, it is possible that combinations of substitutions that constitute each new variant bring about advantages due to a number of factors that are hard to decouple or are yet to be determined. For example, the Indian variant B.1.617.2 (also known as Delta) [59], contains a core number of mutations in Spike (G142D, E154K, L452R, E484Q, D614G, P681R, Q1071H) but also additional sub-strain variations (T95I, H1101D or V382L) [60]. The B.1.617.2 strain and its variations above have predicted open state occupancies comparable or lesser than that of the wild type in our calculations.…”

Analysis of the ARTIC version 3 and version 4 SARS-CoV-2 primers and their impact on the detection of the G142D amino acid substitution in the spike protein

“…These databases have been indispensable for epidemiological analyses, early identification of variants of concern, and downstream translational research activities such as vaccine formulation. From June 2021 through August 2021, the rapid increase in the G142D amino acid substitution present in Delta variants in public repositories appeared to indicate a rapid evolutionary sweep (Fig 1D, Table S1) bearing resemblance to previous evolutionary sweeps, including the D614G substitution in 2020(13), B.1.1.7 (Alpha) last fall and winter (2, 5), and Delta this spring and summer (3, 4). However, our data lead us to conclude that the sharp uptick in spike protein G142D was caused by community adoption of the V4 primers.…”

Flavonols and dihydroflavonols inhibit the main protease activity of SARS-CoV-2 and the replication of human coronavirus 229E

“…It binds to the human angiotensin converting enzyme 2 to help the virus enter the human cells (Hoffmann et al 2020; Yan et al 2020). Since May 2020, the mutations of amino acids of the S protein has created a large number of variants, of which the emergence of alpha, beta, gamma, and delta variants has shown more pathogenic and transmissible, thus caused potential challenges to use vaccines to completely control the pandemic (Abdool Karim and de Oliveira 2021; Walensky et al 2021; Fontanet et al 2021; Altmann et al 2021; Petra et al 2021).…”