Author(s):
Rebelo, Maria ; Tang, Cong ; Coelho, Ana R. ; Labão-Almeida, Carlos ; Schneider, Matthias M. ; Tatalick, Laurie ; Ruivo, Pedro ; de Miranda, Marta Pires ; 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.
Date: 2023
Persistent ID: http://hdl.handle.net/10400.14/42778
Origin: Veritati - Repositório Institucional da Universidade Católica Portuguesa
Subject(s): COVID-19; De novo protein decoys; K18-hACE2 mice; SARS-CoV-2; Treatment
Description
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.
