Antiviral Research. 2022 Jul 30
Minchao Li, Jiaoshan Chen, Yajie Liu, Jin Zhao, Yanjun Li, Yunqi Hu, Yao-qing Chen, Litao Sun, Yuelong Shu, Fengling Feng, and Caijun Sun
Products used in the paper Details Operation
AAV vector packaging AAVrh10 expressing the different ACE2 fragments, including shACE2, shACE2PD, shACE2(PD + Neck), hACE224-83, dACE224-83, were packaged by PackGene Biotech. Request Quote

Research Field: Covid-related

Keywords: COVID-19, SARS-CoV-2, sACE2, Adeno-associated virus (AAV) vector, Variants

AAV Serotype: AAVrh10

Dose: intranasally administered with AAVrh10-GFP, AAVrh10-shACE2, AAVrh10-shACE2(PD + Neck), AAVrh10-hACE224-83, AAVrh10-dACE224-83 with 2 ×10^11 genome copies (GC) in 40 μl volume respectively (5 mice per group).

Animal or cell line strain: 6-8-week-old female BALB/c mice


The frequently emerging SARS-CoV-2 variants have weakened the effectiveness of existing COVID-19 vaccines and neutralizing antibody therapy. Nevertheless, the infections of SARS-CoV-2 variants still depend on angiotensin-converting enzyme 2 (ACE2) receptor-mediated cell entry, and thus the soluble human ACE2 (shACE2) is a potential decoy for broadly blocking SARS-CoV-2 variants. In this study, we firstly generated the recombinant AAVrh10-vectored shACE2 constructs, a kind of adeno-associated virus (AAV) serotype with pulmonary tissue tropism, and then validated its inhibition capacity against SARS-CoV-2 infection. To further optimize the minimized ACE2 functional domain candidates, a comprehensive analysis was performed to clarify the interactions between the ACE2 orthologs from various species and the receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein. Based on the key interface amino acids, we designed a series of truncated ACE2 orthologs, and then assessed their potential affinity to bind to SARS-CoV-2 variants RBD in silico. Of note, we found that the 24-83aa fragment of dog ACE2 (dACE224-83) had a higher affinity to the RBD of SARS-CoV-2 variants than that of human ACE2. Importantly, AAVrh10-vectored shACE2 or dACE224-83 constructs exhibited a broadly blockage breadth against SARS-CoV-2 prototype and variants in vitro and ex vivo. Collectively, these data highlighted a promising therapeutic strategy against SARS-CoV-2 variants.

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