학술논문
De Novo Human Angiotensin-Converting Enzyme 2 Decoy NL-CVX1 Protects Mice From Severe Disease After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.
Document Type
Article
Author
Rebelo, Maria; Tang, Cong; Coelho, Ana R; Labão-Almeida, Carlos; Schneider, Matthias M; Tatalick, Laurie; Ruivo, Pedro; Miranda, Marta Pires de; Gomes, Andreia; Carvalho, Tânia; Walker, Matthew J; Ausserwoeger, Hannes; Simas, J Pedro; Veldhoen, Marc; Knowles, Tuomas P J; Silva, Daniel-Adriano; Shoultz, David; Bernardes, Gonçalo J L
Source
Subject
*COVID-19
*CORONAVIRUS diseases
*SARS-CoV-2
*ANGIOTENSIN converting enzyme
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Language
ISSN
0022-1899
Abstract
The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding domain of the SARS-CoV-2 spike protein. Using a transgenic mouse model of SARS-CoV-2 infection, we showed that a single prophylactic intranasal dose of NL-CVX1 conferred complete protection from severe disease following SARS-CoV-2 infection. Multiple therapeutic administrations of NL-CVX1 also protected mice from succumbing to infection. Finally, we showed that infected mice treated with NL-CVX1 developed both anti-SARS-CoV-2 antibodies and memory T cells and were protected against reinfection a month after treatment. Overall, these observations suggest NL-CVX1 is a promising therapeutic candidate for preventing and treating severe SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]