Biophysical Fitness Landscape of the SARS-CoV-2 Delta Variant Receptor Binding Domain

Patrick, Casey; Upadhyay, Vaibhav; Lucas, Alexandra; Mallela, Krishna

doi:10.1016/j.jmb.2022.167622

Cited by 6 publications

(3 citation statements)

References 82 publications

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“…Our data suggest that mutations at residue 452 (L452R in BA.4/5 and L452Q in BA.2.12.1) may be one of the key drivers of this neutralization resistance phenotype. L452R is also a defining mutation of the Delta variant that has been previously established as granting neutralization resistance (Patrick et al, 2022;Zhang et al, 2022b). Not surprisingly, the new Omicron subvariants containing mutations at 452 are more effectively neutralized by Delta-wave ICU patients.…”

Section: Discussionmentioning

confidence: 99%

Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants

Faraone

Evans

et al. 2022

Preprint

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SummaryThe rising case numbers of the SARS-CoV-2 Omicron BA.4, BA.5, and BA.2.12.1 subvariants has generated serious concern about the course of the pandemic. Here we examine the neutralization resistance, infectivity, processing, and fusogenicity of spike from the BA.4/5 and BA.2.12.1 SARS-CoV-2 variants compared with other Omicron subvariants and Delta. Critically, we found that the new Omicron subvariants BA.4/5 and BA.2.12.1 were more resistant to neutralization by mRNA-vaccinated and boosted health care worker sera and Omicron-BA.1-wave patient sera than were the BA.1 and BA.2 variants. Interestingly, Delta-wave patient sera neutralized more efficiently against not only Delta but also BA.4/5 and BA.2.12.1 variants that also contain substitutions at position L452, similar to Delta. The BA.4/5 and BA.2.12.1 variants also exhibited higher fusogenicity, and increased spike processing, dependent on the L452 substitution. These results highlight the key role of the L452R and L452Q mutations in BA.4/5 and BA.2.12.1 subvariants.

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Section: Discussionmentioning

confidence: 99%

Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants

Faraone

Evans

et al. 2022

Preprint

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“…The therapeutic antibody LY-CoV555 (bamlanivimab) exhibits complete inhibition of binding due to the E484K mutation [ 74 ]. Furthermore, this mutation also decreases the binding affinity of P2B-2F6 to the S protein, thereby restricting the neutralization capability of LY-CoV555 and P2B-2F6 to only the Alpha VOC [ 75 , 76 , 77 ]. In contrast, another antibody, MD65, showing a similar binding profile to LY-CoV555, is not impacted in its binding efficacy by the E484K mutation [ 78 ].…”

Section: Potent Bnabs Against Sars-cov-2mentioning

confidence: 99%

Comprehensive Overview of Broadly Neutralizing Antibodies against SARS-CoV-2 Variants

Cui,

Li,

Xue

et al. 2024

Viruses

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Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about the possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories of broadly neutralizing antibodies (bnAbs) that retain prominent effectiveness against emerging variants including Omicron sub-lineages. The molecular characteristics, epitope conservation, and resistance mechanisms of these antibodies are further detailed, aiming to offer suggestion or direction for the development of therapeutic antibodies, and facilitate the design of vaccines with broad-spectrum potential.

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“…The therapeutic antibody LY-CoV555 (bamlanivimab) experiences complete inhibition of binding due to the E484K mutation [62]. Furthermore, this mutation also decreases the binding affinity of P2B-2F6 to the S protein, thereby restricting the neutralization capability of LY-CoV555 and P2B-2F6 to only the Alpha VOC [63][64][65]. In contrast, another antibody MD65, showing a similar binding profile to LY-CoV555, is not impacted in its binding efficacy by the E484K mutation [66].…”

Section: Class 2 Antibodiesmentioning

confidence: 99%

Comprehensive Overview of Broadly Neutralizing Antibodies against SARS-COV-2 Variants

Cui,

Li,

Xue

et al. 2024

Preprint

View full text Add to dashboard Cite

Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories of broadly neutralizing antibodies (bnAbs) that retain prominent effectiveness against emerging variants including Omicron sub-lineages. The molecular characteristics, epitope conservation, and resistance mechanisms of these antibodies are further detailed, aiming to offer suggestion or direction for the development of therapeutic antibodies, and facilitate the vaccine design with broad-spectrum potential.

show abstract

Biophysical Fitness Landscape of the SARS-CoV-2 Delta Variant Receptor Binding Domain

Cited by 6 publications

References 82 publications

Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants

Differential Evasion of Delta and Omicron Immunity and Enhanced Fusogenicity of SARS-CoV-2 Omicron BA.4/5 and BA.2.12.1 Subvariants

Comprehensive Overview of Broadly Neutralizing Antibodies against SARS-CoV-2 Variants

Comprehensive Overview of Broadly Neutralizing Antibodies against SARS-COV-2 Variants

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