國家衛生研究院 NHRI:Item 3990099045/13543

NHRI > Institute of Biotechnology and Pharmaceutical Research > John Tsu-An Hsu > Periodical Articles > Item 3990099045/13543

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/13543

Title:	The effects of Abeta1-42 binding to the SARS-CoV-2 spike protein S1 subunit and angiotensin-converting enzyme 2
Other Titles:	The effects of Aβ1-42 binding to the SARS-CoV-2 spike protein S1 subunit and angiotensin-converting enzyme 2
Authors:	Hsu, JTA;Tien, CF;Yu, GY;Shen, S;Lee, YH;Hsu, PC;Wang, Y;Chao, PK;Tsay, HJ;Shie, FS
Contributors:	Institute of Biotechnology and Pharmaceutical Research;National Institute of Infectious Diseases and Vaccinology;Center for Neuropsychiatric Research
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 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.
Date:	2021-07-30
Relation:	International Journal of Molecular Sciences. 2021 Jul 30;22(15):Article number 8226.
Link to:	https://doi.org/10.3390/ijms22158226
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000681862700001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85111404142
Appears in Collections:	[John Tsu-An Hsu] Periodical Articles [Guann-Yi Yu] Periodical Articles [Feng-Shiun Shie] Periodical Articles [Yun Wang ] Periodical Articles

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