國家衛生研究院 NHRI:Item 3990099045/13543
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    題名: The effects of Abeta1-42 binding to the SARS-CoV-2 spike protein S1 subunit and angiotensin-converting enzyme 2
    其他題名: The effects of Aβ1-42 binding to the SARS-CoV-2 spike protein S1 subunit and angiotensin-converting enzyme 2
    作者: Hsu, JTA;Tien, CF;Yu, GY;Shen, S;Lee, YH;Hsu, PC;Wang, Y;Chao, PK;Tsay, HJ;Shie, FS
    貢獻者: Institute of Biotechnology and Pharmaceutical Research;National Institute of Infectious Diseases and Vaccinology;Center for Neuropsychiatric Research
    摘要: 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.
    日期: 2021-07-30
    關聯: 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
    顯示於類別:[徐祖安] 期刊論文
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    [王昀] 期刊論文

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