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1.
Int J Mol Sci ; 22(15)2021 Jul 30.
Article in English | MEDLINE | ID: covidwho-1350316

ABSTRACT

Increasing evidence suggests that elderly people with dementia are vulnerable to the development of severe coronavirus disease 2019 (COVID-19). In Alzheimer's disease (AD), the major form of dementia, ß-amyloid (Aß) levels in the blood are increased; however, the impact of elevated Aß levels on the progression of COVID-19 remains largely unknown. Here, our findings demonstrate that Aß1-42, but not Aß1-40, bound to various viral proteins with a preferentially high affinity for the spike protein S1 subunit (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the viral receptor, angiotensin-converting enzyme 2 (ACE2). These bindings were mainly through the C-terminal residues of Aß1-42. Furthermore, Aß1-42 strengthened the binding of the S1 of SARS-CoV-2 to ACE2 and increased the viral entry and production of IL-6 in a SARS-CoV-2 pseudovirus infection model. Intriguingly, data from a surrogate mouse model with intravenous inoculation of Aß1-42 show that the clearance of Aß1-42 in the blood was dampened in the presence of the extracellular domain of the spike protein trimers of SARS-CoV-2, whose effects can be prevented by a novel anti-Aß antibody. In conclusion, these findings suggest that the binding of Aß1-42 to the S1 of SARS-CoV-2 and ACE2 may have a negative impact on the course and severity of SARS-CoV-2 infection. Further investigations are warranted to elucidate the underlying mechanisms and examine whether reducing the level of Aß1-42 in the blood is beneficial to the fight against COVID-19 and AD.


Subject(s)
Amyloid beta-Peptides/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Peptide Fragments/metabolism , SARS-CoV-2/enzymology , Spike Glycoprotein, Coronavirus/metabolism , A549 Cells , Alzheimer Disease/complications , Alzheimer Disease/metabolism , Amyloid beta-Peptides/chemistry , Animals , COVID-19/complications , COVID-19/metabolism , Chlorocebus aethiops , Humans , Interleukin-6/metabolism , Mice, Inbred C57BL , Mice, Transgenic , Peptide Fragments/chemistry , Protein Subunits/chemistry , Protein Subunits/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Vero Cells , Virus Internalization
2.
Int J Mol Sci ; 22(15)2021 Jul 30.
Article in English | MEDLINE | ID: covidwho-1335101

ABSTRACT

Increasing evidence suggests that elderly people with dementia are vulnerable to the development of severe coronavirus disease 2019 (COVID-19). In Alzheimer's disease (AD), the major form of dementia, ß-amyloid (Aß) levels in the blood are increased; however, the impact of elevated Aß levels on the progression of COVID-19 remains largely unknown. Here, our findings demonstrate that Aß1-42, but not Aß1-40, bound to various viral proteins with a preferentially high affinity for the spike protein S1 subunit (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the viral receptor, angiotensin-converting enzyme 2 (ACE2). These bindings were mainly through the C-terminal residues of Aß1-42. Furthermore, Aß1-42 strengthened the binding of the S1 of SARS-CoV-2 to ACE2 and increased the viral entry and production of IL-6 in a SARS-CoV-2 pseudovirus infection model. Intriguingly, data from a surrogate mouse model with intravenous inoculation of Aß1-42 show that the clearance of Aß1-42 in the blood was dampened in the presence of the extracellular domain of the spike protein trimers of SARS-CoV-2, whose effects can be prevented by a novel anti-Aß antibody. In conclusion, these findings suggest that the binding of Aß1-42 to the S1 of SARS-CoV-2 and ACE2 may have a negative impact on the course and severity of SARS-CoV-2 infection. Further investigations are warranted to elucidate the underlying mechanisms and examine whether reducing the level of Aß1-42 in the blood is beneficial to the fight against COVID-19 and AD.


Subject(s)
Amyloid beta-Peptides/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Peptide Fragments/metabolism , SARS-CoV-2/enzymology , Spike Glycoprotein, Coronavirus/metabolism , A549 Cells , Alzheimer Disease/complications , Alzheimer Disease/metabolism , Amyloid beta-Peptides/chemistry , Animals , COVID-19/complications , COVID-19/metabolism , Chlorocebus aethiops , Humans , Interleukin-6/metabolism , Mice, Inbred C57BL , Mice, Transgenic , Peptide Fragments/chemistry , Protein Subunits/chemistry , Protein Subunits/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Vero Cells , Virus Internalization
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