tetano
Editor, Senior Moderator
Int J Mol Sci
. 2021 Jul 30;22(15):8226.
doi: 10.3390/ijms22158226.
The Effects of Aβ [SUB]1-42[/SUB] Binding to the SARS-CoV-2 Spike Protein S1 Subunit and Angiotensin-Converting Enzyme 2
John Tsu-An Hsu[SUP] 1 [/SUP], Chih-Feng Tien[SUP] 2 [/SUP], Guann-Yi Yu[SUP] 2 [/SUP], Santai Shen[SUP] 3 [/SUP], Yi-Hsuan Lee[SUP] 4 5 [/SUP], Pei-Chien Hsu[SUP] 4 5 [/SUP], Yun Wang[SUP] 6 [/SUP], Po-Kuan Chao[SUP] 6 [/SUP], Huey-Jen Tsay[SUP] 7 [/SUP], Feng-Shiun Shie[SUP] 6 [/SUP]
Affiliations
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, β-amyloid (Aβ) levels in the blood are increased; however, the impact of elevated Aβ levels on the progression of COVID-19 remains largely unknown. Here, our findings demonstrate that Aβ[SUB]1-42[/SUB], but not Aβ[SUB]1-40[/SUB], 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 Aβ[SUB]1-42[/SUB]. Furthermore, Aβ[SUB]1-42[/SUB] 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 Aβ[SUB]1-42[/SUB] show that the clearance of Aβ[SUB]1-42[/SUB] 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-Aβ antibody. In conclusion, these findings suggest that the binding of Aβ[SUB]1-42[/SUB] 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 Aβ[SUB]1-42[/SUB] in the blood is beneficial to the fight against COVID-19 and AD.
Keywords: ACE2; Alzheimer’s disease; Aβ; COVID-19; SARS-CoV-2 spike protein.
. 2021 Jul 30;22(15):8226.
doi: 10.3390/ijms22158226.
The Effects of Aβ [SUB]1-42[/SUB] Binding to the SARS-CoV-2 Spike Protein S1 Subunit and Angiotensin-Converting Enzyme 2
John Tsu-An Hsu[SUP] 1 [/SUP], Chih-Feng Tien[SUP] 2 [/SUP], Guann-Yi Yu[SUP] 2 [/SUP], Santai Shen[SUP] 3 [/SUP], Yi-Hsuan Lee[SUP] 4 5 [/SUP], Pei-Chien Hsu[SUP] 4 5 [/SUP], Yun Wang[SUP] 6 [/SUP], Po-Kuan Chao[SUP] 6 [/SUP], Huey-Jen Tsay[SUP] 7 [/SUP], Feng-Shiun Shie[SUP] 6 [/SUP]
Affiliations
- PMID: 34360989
- DOI: 10.3390/ijms22158226
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, β-amyloid (Aβ) levels in the blood are increased; however, the impact of elevated Aβ levels on the progression of COVID-19 remains largely unknown. Here, our findings demonstrate that Aβ[SUB]1-42[/SUB], but not Aβ[SUB]1-40[/SUB], 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 Aβ[SUB]1-42[/SUB]. Furthermore, Aβ[SUB]1-42[/SUB] 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 Aβ[SUB]1-42[/SUB] show that the clearance of Aβ[SUB]1-42[/SUB] 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-Aβ antibody. In conclusion, these findings suggest that the binding of Aβ[SUB]1-42[/SUB] 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 Aβ[SUB]1-42[/SUB] in the blood is beneficial to the fight against COVID-19 and AD.
Keywords: ACE2; Alzheimer’s disease; Aβ; COVID-19; SARS-CoV-2 spike protein.