PMID- 36555121
OWN - NLM
STAT- MEDLINE
DCOM- 20230103
LR  - 20230103
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 24
DP  - 2022 Dec 7
TI  - SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 
      Morbidities and Therapeutics and for Vaccine Adverse Effects.
LID - 10.3390/ijms232415480 [doi]
LID - 15480
AB  - Experimental findings for SARS-CoV-2 related to the glycan biochemistry of 
      coronaviruses indicate that attachments from spike protein to glycoconjugates on 
      the surfaces of red blood cells (RBCs), other blood cells and endothelial cells 
      are key to the infectivity and morbidity of COVID-19. To provide further insight 
      into these glycan attachments and their potential clinical relevance, the classic 
      hemagglutination (HA) assay was applied using spike protein from the Wuhan, 
      Alpha, Delta and Omicron B.1.1.529 lineages of SARS-CoV-2 mixed with human RBCs. 
      The electrostatic potential of the central region of spike protein from these 
      four lineages was studied through molecular modeling simulations. Inhibition of 
      spike protein-induced HA was tested using the macrocyclic lactone ivermectin 
      (IVM), which is indicated to bind strongly to SARS-CoV-2 spike protein glycan 
      sites. The results of these experiments were, first, that spike protein from 
      these four lineages of SARS-CoV-2 induced HA. Omicron induced HA at a 
      significantly lower threshold concentration of spike protein than the three prior 
      lineages and was much more electropositive on its central spike protein region. 
      IVM blocked HA when added to RBCs prior to spike protein and reversed HA when 
      added afterward. These results validate and extend prior findings on the role of 
      glycan bindings of viral spike protein in COVID-19. They furthermore suggest 
      therapeutic options using competitive glycan-binding agents such as IVM and may 
      help elucidate rare serious adverse effects (AEs) associated with COVID-19 mRNA 
      vaccines, which use spike protein as the generated antigen.
FAU - Boschi, Celine
AU  - Boschi C
AD  - MEPHI, Aix-Marseille Universite, Institut de Recherche Pour le Developpement 
      (IRD), Assistance Publique-Hopitaux de Marseille (AP-HM), IHU Mediterranee 
      Infection, 13005 Marseille, France.
FAU - Scheim, David E
AU  - Scheim DE
AUID- ORCID: 0000-0001-6841-7054
AD  - US Public Health Service, Commissioned Officer, Inactive Reserve, Blacksburg, VA 
      24060, USA.
FAU - Bancod, Audrey
AU  - Bancod A
AD  - MEPHI, Aix-Marseille Universite, Institut de Recherche Pour le Developpement 
      (IRD), Assistance Publique-Hopitaux de Marseille (AP-HM), IHU Mediterranee 
      Infection, 13005 Marseille, France.
FAU - Militello, Muriel
AU  - Militello M
AD  - MEPHI, Aix-Marseille Universite, Institut de Recherche Pour le Developpement 
      (IRD), Assistance Publique-Hopitaux de Marseille (AP-HM), IHU Mediterranee 
      Infection, 13005 Marseille, France.
FAU - Bideau, Marion Le
AU  - Bideau ML
AD  - MEPHI, Aix-Marseille Universite, Institut de Recherche Pour le Developpement 
      (IRD), Assistance Publique-Hopitaux de Marseille (AP-HM), IHU Mediterranee 
      Infection, 13005 Marseille, France.
FAU - Colson, Philippe
AU  - Colson P
AUID- ORCID: 0000-0001-6285-0308
AD  - MEPHI, Aix-Marseille Universite, Institut de Recherche Pour le Developpement 
      (IRD), Assistance Publique-Hopitaux de Marseille (AP-HM), IHU Mediterranee 
      Infection, 13005 Marseille, France.
FAU - Fantini, Jacques
AU  - Fantini J
AUID- ORCID: 0000-0001-8653-5521
AD  - INSERM UMR S 1072, Aix-Marseille Universite, 13015 Marseille, France.
FAU - Scola, Bernard La
AU  - Scola B
AUID- ORCID: 0000-0001-8006-7704
AD  - MEPHI, Aix-Marseille Universite, Institut de Recherche Pour le Developpement 
      (IRD), Assistance Publique-Hopitaux de Marseille (AP-HM), IHU Mediterranee 
      Infection, 13005 Marseille, France.
LA  - eng
GR  - 10-IAHU-03/This work was supported by the French Government under the 
      "Investments for the Future" programme managed by the National Agency for 
      Research (ANR), Mediterranee-Infection 10-IAHU-03/
PT  - Journal Article
DEP - 20221207
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antibodies, Viral)
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - 0 (COVID-19 Vaccines)
SB  - IM
MH  - Humans
MH  - Antibodies, Viral
MH  - *COVID-19
MH  - Endothelial Cells
MH  - *Hemagglutination
MH  - SARS-CoV-2
MH  - *Spike Glycoprotein, Coronavirus
MH  - *COVID-19 Vaccines/adverse effects
PMC - PMC9779393
OTO - NOTNLM
OT  - CD147
OT  - COVID-19
OT  - SARS-CoV-2
OT  - electrostatic charge
OT  - glycophorin A
OT  - hemagglutination
OT  - sialic acid
OT  - spike protein
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/24 06:00
MHDA- 2022/12/27 06:00
PMCR- 2022/12/07
CRDT- 2022/12/23 01:32
PHST- 2022/11/25 00:00 [received]
PHST- 2022/12/02 00:00 [revised]
PHST- 2022/12/03 00:00 [accepted]
PHST- 2022/12/23 01:32 [entrez]
PHST- 2022/12/24 06:00 [pubmed]
PHST- 2022/12/27 06:00 [medline]
PHST- 2022/12/07 00:00 [pmc-release]
AID - ijms232415480 [pii]
AID - ijms-23-15480 [pii]
AID - 10.3390/ijms232415480 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Dec 7;23(24):15480. doi: 10.3390/ijms232415480.