The effects of Aβ1-42 binding to the SARS-CoV-2 spike protein S1 subunit and angiotensin-converting enzyme 2

John Tsu An Hsu, Chih Feng Tien, Guann Yi Yu, Santai Shen, Yi Hsuan Lee, Pei Chien Hsu, Yun Wang, Po Kuan Chao, Huey Jen Tsay, Feng Shiun Shie*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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 demon-strate 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 ex-amine whether reducing the level of Aβ1-42 in the blood is beneficial to the fight against COVID-19 and AD.

Original languageEnglish
Article number8226
JournalInternational Journal Of Molecular Sciences
Issue number15
StatePublished - 1 Aug 2021


  • ACE2
  • Alzheimer’s disease
  • COVID-19
  • SARS-CoV-2 spike protein


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