Emerging anti-spike monoclonal antibodies against SARS-CoV-2

Ordaya, Eloy E.; Razonable, Raymund R.

doi:10.1080/14712598.2024.2326647

Cited by 1 publication

(1 citation statement)

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“…Beside chemical TLR4 antagonists, antibody-based therapies targeting TLR4/MD-2 binding and/or dimerization may be highly interesting considering the high binding affinity and specificity, and the good safety profile shown for humanized monoclonal antibodies [110], or recent further developments, such as nanobodies [111]. Still, antibodybased therapies will face similar challenges encountered by previous agents, such as a continued evolution of SARS-CoV-2 and emergence of new escape mutations, in particular for the ACE2 binding RBD of the spike protein, as a major force for generation of new virus variants.…”

Section: Discussionmentioning

confidence: 99%

In Silico Analyses Indicate a Lower Potency for Dimerization of TLR4/MD-2 as the Reason for the Lower Pathogenicity of Omicron Compared to Wild-Type Virus and Earlier SARS-CoV-2 Variants

Kircheis

2024

IJMS

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The SARS-CoV-2 Omicron variants have replaced all earlier variants, due to increased infectivity and effective evasion from infection- and vaccination-induced neutralizing antibodies. Compared to earlier variants of concern (VoCs), the Omicron variants show high TMPRSS2-independent replication in the upper airway organs, but lower replication in the lungs and lower mortality rates. The shift in cellular tropism and towards lower pathogenicity of Omicron was hypothesized to correlate with a lower toll-like receptor (TLR) activation, although the underlying molecular mechanisms remained undefined. In silico analyses presented here indicate that the Omicron spike protein has a lower potency to induce dimerization of TLR4/MD-2 compared to wild type virus despite a comparable binding activity to TLR4. A model illustrating the molecular consequences of the different potencies of the Omicron spike protein vs. wild-type spike protein for TLR4 activation is presented. Further analyses indicate a clear tendency for decreasing TLR4 dimerization potential during SARS-CoV-2 evolution via Alpha to Gamma to Delta to Omicron variants.

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Section: Discussionmentioning

confidence: 99%

In Silico Analyses Indicate a Lower Potency for Dimerization of TLR4/MD-2 as the Reason for the Lower Pathogenicity of Omicron Compared to Wild-Type Virus and Earlier SARS-CoV-2 Variants

Kircheis

2024

IJMS

View full text Add to dashboard Cite

show abstract

Emerging anti-spike monoclonal antibodies against SARS-CoV-2

Cited by 1 publication

References 50 publications

In Silico Analyses Indicate a Lower Potency for Dimerization of TLR4/MD-2 as the Reason for the Lower Pathogenicity of Omicron Compared to Wild-Type Virus and Earlier SARS-CoV-2 Variants

In Silico Analyses Indicate a Lower Potency for Dimerization of TLR4/MD-2 as the Reason for the Lower Pathogenicity of Omicron Compared to Wild-Type Virus and Earlier SARS-CoV-2 Variants

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