SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects
Boschi et al.,
SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and..,
bioRxiv, doi:10.1101/2022.11.24.517882 (Preprint) (In Vitro)
In Vitro study showing that ivermectin blocked hemagglutination (clumping of red blood cells) when added to red blood cells prior to SARS-CoV-2 spike protein, and reversed hemagglutination when added afterwards.
Spike protein from four lineages of SARS-CoV-2 induced hemagglutination in human red blood cells, with omicron inducing hemagglutination at a significantly lower concentration. Authors note that the results supports other indications that spike protein-induced red blood cell clumping, as well as viral attachments to other blood cells and endothelial cells, may be a significant factor in COVID-19 morbidities.
15 In Vitro studies support the efficacy of ivermectin
[Boschi, Caly, Croci, De Forni, Delandre, Jeffreys, Jitobaom, Jitobaom (B), Li, Liu, Mody, Mountain Valley MD, Segatori, Surnar, Yesilbag].
Boschi et al., 28 Nov 2022, France, preprint, 8 authors.
Contact:
dscheim@alum.mit.edu (corresponding author), bernard.la-scola@univamu.fr.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: bioRxiv preprint doi: https://doi.org/10.1101/2022.11.24.517882; this version posted November 28, 2022. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
available under aCC-BY-NC-ND 4.0 International license.
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SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19
Morbidities and Therapeutics and for Vaccine Adverse Effects
Celine Boschi1, David E. Scheim2*, Audrey Bancod1, Muriel Millitello1, Marion Le Bideau1,
Philippe Colson1, Jacques Fantini3, Bernard La Scola1*
1
MEPHI, Aix-Marseille Université, Institut de Recherche pour le Développement (IRD),
Assistance Publique - Hôpitaux de Marseille (AP-HM), IHU Méditerranée Infection, 13005
Marseille, France
2
US Public Health Service, Commissioned Officer, Inactive Reserve, Blacksburg, VA 24060,
USA
3
INSERM UMR S 1072, Aix-Marseille Université, 13015 Marseille, France
*Correspondence: dscheim@alum.mit.edu, Tel.: +1 540 3208013; bernard.la-scola@univamu.fr, Tel.: +33 413732401
Keywords:
SARS-CoV-2; COVID-19; spike protein; hemagglutination; sialic acid; CD147;
electrostatic charge; glycophorin A
bioRxiv preprint doi: https://doi.org/10.1101/2022.11.24.517882; this version posted November 28, 2022. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made
available under aCC-BY-NC-ND 4.0 International license.
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ABSTRACT
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Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses
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indicate that attachments from spike protein to glycoconjugates on the surfaces of red blood cells
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(RBCs), other blood cells and endothelial cells are key to the infectivity and morbidity of COVID-
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19. To provide further insight into these glycan attachments and their potential clinical relevance,
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the classic hemagglutination (HA) assay was applied using spike protein from the Wuhan, Alpha,
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Delta and Omicron B.1.1.529 lineages of SARS-CoV-2 mixed with human RBCs. The
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electrostatic potential of the central region of spike protein from these four lineages was studied
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through molecular modeling simulations. Inhibition of spike protein-induced HA was tested using
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the macrocyclic lactone ivermectin (IVM), which is indicated to bind strongly to SARS-CoV-2
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spike protein glycan sites. The results of these experiments were, first, that spike protein from
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these four lineages of SARS-CoV-2 induced HA. Omicron induced HA at a significantly lower
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threshold concentration of spike protein than for the three prior lineages and was much more
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electropositive on its central spike protein region. IVM blocked HA when added to RBCs prior to
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spike protein and reversed HA when added afterwards. These results validate and extend prior
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findings on the role of glycan bindings of viral spike protein in COVID-19. They furthermore
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suggest therapeutic options using competitive glycan-binding agents such as IVM and may help
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elucidate rare serious adverse effects (AEs) associated with COVID-19 mRNA vaccines which
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use spike protein as the generated antigen.
bioRxiv preprint doi: https://doi.org/10.1101/2022.11.24.517882; this version posted November 28, 2022. The copyright holder for this..
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