SARS-CoV-2 receptor binding domain radio-probe: a non-invasive approach for angiotensin-converting enzyme 2 mapping in mice.
|
| Abstract |
The spike protein of SARS-CoV-2 interacts with angiotensin-converting enzyme 2 (ACE2) of human respiratory epithelial cells, which leads to infection. Furthermore, low-dose radiation has been found to reduce inflammation and aid the curing of COVID-19. The receptor binding domain (RBD), a recombinant spike protein with a His tag at the C-terminus, binds to ACE2 in human body. We thus constructed a radioiodinated RBD as a molecule-targeted probe to non-invasively explore ACE2 expression in vivo, and to investigate radiotherapy pathway for inhibiting ACE2. RBD was labeled with [124I]NaI using an N-bromosuccinimide (NBS)-mediated method, and 124I-RBD was obtained after purification with a specific activity of 28.9 GBq/nmol. Its radiochemical purity was (RCP) over 90% in saline for 5 days. The dissociation constant of 124I-RBD binding to hACE2 was 75.7 nM. The uptake of 124I-RBD by HeLaACE+ cells at 2 h was 2.96% ± 0.35%, which could be substantially blocked by an excessive amount of RBD, and drop to 1.71% ± 0.23%. In BALB/c mice, the biodistribution of 124I-RBD after intravenous injection showed a moderate metabolism rate, and its 24 h-post injection (p.i.) organ distribution was similar to the expression profile in body. Micro-PET imaging of mice after intrapulmonary injection showed high uptake of lung at 1, 4, 24 h p.i.. In conclusion, the experimental results demonstrate the potential of 124I-RBD as a novel targeted molecular probe for COVID-19. This probe may be used for non-invasive ACE2 mapping in mammals.
|
|---|---|
| Authors | Dan Li, Jin Ding, Te-Li Liu, Feng Wang, Xiang-Xi Meng, Song Liu, Zhi Yang, Hua Zhu |
| Journal | Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 43 Issue 7 Pg. 1749-1757 (Jul 2022) ISSN: 1745-7254 [Electronic] United States |
| PMID | 34815544 (Publication Type: Journal Article) |
| Copyright | © 2021. The Author(s), under exclusive licence to CPS and SIMM. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!