Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: implications for the vaccine

Kanduc, Darja; Shoenfeld, Yehuda

doi:10.1007/s12026-020-09152-6

Cited by 220 publications

(205 citation statements)

References 30 publications

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“…For example, the SARS-CoV-2 S1/S2 cleavage site mimics an identical furin-cleavable peptide on the human epithelial sodium channel α-subunit [ 54 ]. Several peptides encoded by SARS-CoV-2 and SARS-CoV, including at the S2 domain, were also found to have high sequence homology with human proteins [ 55 , 56 ]. Moreover, these similarities have been found in human peptides known to bind MHC class-I molecules, identifying peptide mimicry as a mode of immune evasion by SARS-CoV-2 [ 57 ].…”

Section: Viral Defense Mechanisms For Antibody Evasionmentioning

confidence: 99%

Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies

Finkelstein

Mermelstein

Miller

et al. 2021

Viruses

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Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike’s receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure and clinical applications. We also place mAbs against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses in the context of the SARS-CoV-2 spike to suggest features that may be desirable to design mAbs or vaccines capable of conferring broad protection.

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Section: Viral Defense Mechanisms For Antibody Evasionmentioning

confidence: 99%

Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies

Finkelstein

Mermelstein

Miller

et al. 2021

Viruses

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“…They suggested that because the SARS-CoV-2 and lung surfactant proteins shared 13 out of 24 pentapeptides, the immune response following infection with SARS-CoV-2 may lead to cross-reactions with pulmonary surfactant proteins, followed by SARS-CoV-2–associated lung disease ( 9 ). Furthermore, very recently they presented indisputable proof of molecular mimicry as a potential mechanism for contributing to SARS-CoV-2 associated diseases ( 10 ). Based on their findings, they warned against the use of the entire SARS-CoV-2 antigens in the vaccines and cautioned that perhaps the use of only unique peptides would be the most effective way to fight the SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases

Vojdani²,

2021

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We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases. Very recently, human monoclonal antibodies were approved for use on patients with COVID-19. The human monoclonal antibodies used in this study are almost identical with these approved antibodies. Thus, our results can establish the potential risk for autoimmunity and multi-system disorders with COVID-19 that may come from cross-reactivity between our own human tissues and this dreaded virus, and thus ensure that the badly-needed vaccines and treatments being developed for it are truly safe to use against this disease.

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“…This risk of cross-reactivity further increases when considering that it cannot be estimated with the current vaccine pre-clinical tests [ 153 , 154 ]. Indeed, the level of peptide sharing is highest between pathogens and human, murine, and rat proteomes, and is lowest (or absent) with proteomes from nonhuman primates such as gorilla, chimpanzee, and rhesus macaque.…”

Section: Resultsmentioning

confidence: 99%

Vaccine- and natural infection-induced mechanisms that could modulate vaccine safety

et al. 2020

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Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: implications for the vaccine

Cited by 220 publications

References 30 publications

Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies

Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies

Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases

Vaccine- and natural infection-induced mechanisms that could modulate vaccine safety

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