The Effects of Aβ1-42 Binding to the SARS-CoV-2 Spike Protein S1 Subunit and Angiotensin-Converting Enzyme 2

• Published in: International journal of molecular sciences Vol. 22; no. 15; p. 8226
• Main Authors: Hsu, John Tsu-An, Tien, Chih-Feng, Yu, Guann-Yi, Shen, Santai, Lee, Yi-Hsuan, Hsu, Pei-Chien, Wang, Yun, Chao, Po-Kuan, Tsay, Huey-Jen, Shie, Feng-Shiun
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 30.07.2021; MDPI
• Subjects: ACE2; Alzheimer's disease; Angiotensin; Angiotensin-converting enzyme 2; Binding; Blood; Conversion; Coronaviruses; COVID-19; Dementia disorders; Inoculation; Interleukin 6; Intravenous administration; Middle East respiratory syndrome; Mutation; Older people; Peptidyl-dipeptidase A; Proteins; Respiratory diseases; SARS-CoV-2 spike protein; Severe acute respiratory syndrome coronavirus 2; Spike protein; Viral diseases; Viral infections; β-Amyloid
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22158226

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 Aβ1-42, but not Aβ1-40, 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 Aβ1-42. Furthermore, Aβ1-42 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 Aβ1-42 show that the clearance of Aβ1-42 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-Aβ antibody. In conclusion, these findings suggest that the binding of Aβ1-42 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 Aβ1-42 in the blood is beneficial to the fight against COVID-19 and AD.