De novo human angiotensin - converting enzyme 2 Decoy NL-CVX1 protects mice from severe disease after severe acute respiratory syndrome coronavirus 2 infection

Maria Rebelo, Cong Tang, Ana R. Coelho, Carlos Labão-Almeida, Matthias M. Schneider, Laurie Tatalick, Pedro Ruivo, Marta Pires de Miranda, Andreia Gomes, Tânia Carvalho, Matthew J. Walker, Hannes Ausserwoeger, J. Pedro Simas, Marc Veldhoen, Tuomas P. J. Knowles, Daniel Adriano Silva, David Shoultz, Gonçalo J. L. Bernardes

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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.

Original languageEnglish
Pages (from-to)723-733
Number of pages11
JournalThe Journal of infectious diseases
Volume228
Issue number6
DOIs
Publication statusPublished - 15 Sept 2023

Keywords

  • COVID-19
  • De novo protein decoys
  • K18-hACE2 mice
  • SARS-CoV-2
  • Treatment

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