tetano
Editor, Senior Moderator
J Infect Dis
. 2023 Jun 5;jiad135.
doi: 10.1093/infdis/jiad135. Online ahead of print. 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[SUP] 1 [/SUP], Cong Tang[SUP] 1 [/SUP], Ana R Coelho[SUP] 1 [/SUP], Carlos Labão-Almeida[SUP] 1 [/SUP], Matthias M Schneider[SUP] 2 [/SUP], Laurie Tatalick[SUP] 3 [/SUP], Pedro Ruivo[SUP] 1 [/SUP], Marta Pires de Miranda[SUP] 1 [/SUP], Andreia Gomes[SUP] 1 [/SUP], Tânia Carvalho[SUP] 4 [/SUP], Matthew J Walker[SUP] 5 [/SUP], Hannes Ausserwoeger[SUP] 2 [/SUP], J Pedro Simas[SUP] 1 6 [/SUP], Marc Veldhoen[SUP] 1 [/SUP], Tuomas P J Knowles[SUP] 2 [/SUP], Daniel-Adriano Silva[SUP] 5 [/SUP], David Shoultz[SUP] 5 [/SUP], Gonçalo J L Bernardes[SUP] 1 2 [/SUP]
Affiliations
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.
Keywords: COVID-19; SARS-CoV-2; de novo protein decoys; k18-hACE2 mice; treatment.
. 2023 Jun 5;jiad135.
doi: 10.1093/infdis/jiad135. Online ahead of print. 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[SUP] 1 [/SUP], Cong Tang[SUP] 1 [/SUP], Ana R Coelho[SUP] 1 [/SUP], Carlos Labão-Almeida[SUP] 1 [/SUP], Matthias M Schneider[SUP] 2 [/SUP], Laurie Tatalick[SUP] 3 [/SUP], Pedro Ruivo[SUP] 1 [/SUP], Marta Pires de Miranda[SUP] 1 [/SUP], Andreia Gomes[SUP] 1 [/SUP], Tânia Carvalho[SUP] 4 [/SUP], Matthew J Walker[SUP] 5 [/SUP], Hannes Ausserwoeger[SUP] 2 [/SUP], J Pedro Simas[SUP] 1 6 [/SUP], Marc Veldhoen[SUP] 1 [/SUP], Tuomas P J Knowles[SUP] 2 [/SUP], Daniel-Adriano Silva[SUP] 5 [/SUP], David Shoultz[SUP] 5 [/SUP], Gonçalo J L Bernardes[SUP] 1 2 [/SUP]
Affiliations
- PMID: 37279654
- DOI: 10.1093/infdis/jiad135
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.
Keywords: COVID-19; SARS-CoV-2; de novo protein decoys; k18-hACE2 mice; treatment.