Predicted structural mimicry of spike receptor-binding motifs from highly pathogenic human coronaviruses

Beaudoin, Christopher; Jamasb, Arian R.; Alsulami, Ali; Copoiu, Liviu; Tonder, Andries J. van; Hala, Sharif; Bannerman, Bridget P.; Thomas, S.E.; Vedithi, Sundeep Chaitanya; Torres, Pedro H M; Blundell, Tom L.

doi:10.1101/2021.04.23.441187

Cited by 4 publications

(3 citation statements)

References 175 publications

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“…Furthermore, the extended comparisons on sequence, structural and chemical levels reveal more areas of relevance. For instance, these multi-level similarities could hint for linked expression patterns with host genes, sharing or hijacking 44,56,57,58,59 regulatory relationships like transcription factors, miRNAs and immune system evasion or regulatory mechanisms 52,60,61,62 .…”

Section: Discussionmentioning

confidence: 99%

Identifying and profiling structural similarities between Spike of SARS-CoV-2 and other viral or host proteins with Machaon

Kakoulidis

Vlachos

Thanos

et al. 2022

Preprint

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Using protein structure to predict function, interactions, and evolutionary history is still an open challenge, with existing approaches relying extensively on protein homology and families. Here, we present Machaon, a new data-driven method combining orientation invariant metrics on phi-psi angles, inter-residue contacts and surface complexity. It can be readily applied on whole structures or segments—such as domains and binding sites. Machaon was applied on SARS-CoV-2 Spike monomers of native, Delta and Omicron variants and identified correlations with a wide range of viral proteins from close to distant taxonomy ranks, as well as host receptors, such as ACE2. The associated whole structures have: 32.7% and 38.5% sequence identities on protein secondary structure and gene coding region, 86% chemical and 22.1% protein tertiary structure similarities (median values, native Spike). Machaon’s meta-analysis revealed Spike’s relationships with biological processes such as ubiquitination and angiogenesis and highlighted different patterns in virus attachment among the studied variants. Available at: https://github.com/anastasiadoulab/machaon .

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Section: Discussionmentioning

confidence: 99%

Identifying and profiling structural similarities between Spike of SARS-CoV-2 and other viral or host proteins with Machaon

Kakoulidis

Vlachos

Thanos

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Exposure to viral epitopes is an identified cause of autoimmunity, previously advanced in infectious diseases with other coronaviruses 2,3 . Molecular mimicry between SARS-CoV-2 protein and self-antigen has been proposed as an autoimmune trigger in patients genetically prone [4][5][6] . Cells infected with SARS-CoV-2 can escape type I interferon (IFN) response, leading to an uncontrolled viral replication 7 .…”

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confidence: 99%

“…4 Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France. 5 Aix-Marseille Univ, IRD, MEPHI, IHU-Méditerranée Infection, Marseille, France. 6 These authors contributed equally: Daniel Bertin and Alexandre Brodovitch.…”

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confidence: 99%

Anti-cardiolipin IgG autoantibodies associate with circulating extracellular DNA in severe COVID-19

Bertin

Brodovitch

López

et al. 2022

Sci Rep

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Whereas the detection of antiphospholipid autoantibodies (aPL) in COVID-19 is of increasing interest, their role is still unclear. We analyzed a large aPL panel in 157 patients with COVID-19 according to the disease severity. We also investigated a potential association between aPL and extracellular DNA (exDNA, n = 85) or circulating markers of neutrophil extracellular traps (NET) such as citrullinated histones H3 (CitH3, n = 49). A total of 157 sera of patients infected by SARS-CoV-2 were collected. A large aPL panel including lupus anticoagulant, anti-cardiolipin and anti-beta-2 glycoprotein I (IgG, IgM and IgA), anti-phosphatidylethanolamine IgA, anti-prothrombin (IgG and IgM) was retrospectively analyzed according to the disease severity. We found a total aPL prevalence of 54.8% with almost half of the cases having aCL IgG. Within an extended panel of aPL, only aCL IgG were associated with COVID-19 severity. Additionally, severe patients displayed higher CitH3 levels than mild patients. Interestingly, we highlighted a significant association between the levels of aCL IgG and exDNA only in aCL positive patients with severe disease. In conclusion, we showed a significant link between aPL, namely aCL IgG, and circulating exDNA in patients with severe form of COVID-19, that could exacerbate the thrombo-inflammatory state related to disease severity.

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The roles of Eph receptors, neuropilin-1, P2X7, and CD147 in COVID-19-associated neurodegenerative diseases: inflammasome and JaK inhibitors as potential promising therapies

et al. 2022

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The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and finding a safe therapeutic strategy and effective vaccine is critical to overcoming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, elucidation of pathogenesis mechanisms, especially entry routes of SARS-CoV-2 may help propose antiviral drugs and novel vaccines. Several receptors have been demonstrated for the interaction of spike (S) protein of SARS-CoV-2 with host cells, including angiotensin-converting enzyme (ACE2), ephrin ligands and Eph receptors, neuropilin 1 (NRP-1), P2X7, and CD147. The expression of these entry receptors in the central nervous system (CNS) may make the CNS prone to SARS-CoV-2 invasion, leading to neurodegenerative diseases. The present review provides potential pathological mechanisms of SARS-CoV-2 infection in the CNS, including entry receptors and cytokines involved in neuroinflammatory conditions. Moreover, it explains several neurodegenerative disorders associated with COVID-19. Finally, we suggest inflammasome and JaK inhibitors as potential therapeutic strategies for neurodegenerative diseases.

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Predicted structural mimicry of spike receptor-binding motifs from highly pathogenic human coronaviruses

Cited by 4 publications

References 175 publications

Identifying and profiling structural similarities between Spike of SARS-CoV-2 and other viral or host proteins with Machaon

Identifying and profiling structural similarities between Spike of SARS-CoV-2 and other viral or host proteins with Machaon

Anti-cardiolipin IgG autoantibodies associate with circulating extracellular DNA in severe COVID-19

The roles of Eph receptors, neuropilin-1, P2X7, and CD147 in COVID-19-associated neurodegenerative diseases: inflammasome and JaK inhibitors as potential promising therapies

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