Your browser doesn't support javascript.
The Effects of Aß1-42 Binding to the SARS-CoV-2 Spike Protein S1 Subunit and Angiotensin-Converting Enzyme 2.
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.
  • Hsu JT; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan.
  • Tien CF; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County 35053, Taiwan.
  • Yu GY; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County 35053, Taiwan.
  • Shen S; Antaimmu BioMed Co., Ltd., Hsinchu 30078, Taiwan.
  • Lee YH; Department and Institute of Physiology, National Yang-Ming University, Taipei 11221, Taiwan.
  • Hsu PC; Department and Institute of Physiology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
  • Wang Y; Department and Institute of Physiology, National Yang-Ming University, Taipei 11221, Taiwan.
  • Chao PK; Department and Institute of Physiology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
  • Tsay HJ; Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County 35053, Taiwan.
  • Shie FS; Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County 35053, Taiwan.
Int J Mol Sci ; 22(15)2021 Jul 30.
Article in English | MEDLINE | ID: covidwho-1350316
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, ß-amyloid (Aß) levels in the blood are increased; however, the impact of elevated Aß levels on the progression of COVID-19 remains largely unknown. Here, our findings demonstrate that Aß1-42, but not Aß1-40, 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 Aß1-42. Furthermore, Aß1-42 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 Aß1-42 show that the clearance of Aß1-42 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-Aß antibody. In conclusion, these findings suggest that the binding of Aß1-42 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 Aß1-42 in the blood is beneficial to the fight against COVID-19 and AD.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Peptide Fragments / Amyloid beta-Peptides / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Subject: Peptide Fragments / Amyloid beta-Peptides / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Type of study: Prognostic study Language: English Clinical aspect: Prognosis Year: 2021

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Peptide Fragments / Amyloid beta-Peptides / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Subject: Peptide Fragments / Amyloid beta-Peptides / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Type of study: Prognostic study Language: English Clinical aspect: Prognosis Year: 2021
...