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

doi:10.1093/infdis/jiad135

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	723-733
Number of pages	11
Journal	The Journal of infectious diseases
Volume	228
Issue number	6
DOIs	https://doi.org/10.1093/infdis/jiad135
Publication status	Published - 15 Sept 2023

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/infdis/jiad135Licence: CC BY

75478747Final published version, 1.15 MBLicence: CC BY

http://hdl.handle.net/10400.14/42778Licence: CC BY

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Rebelo, M., Tang, C., Coelho, A. R., Labão-Almeida, C., Schneider, M. M., Tatalick, L., Ruivo, P., Miranda, M. P. D., Gomes, A., Carvalho, T., Walker, M. J., Ausserwoeger, H., Simas, J. P., Veldhoen, M., Knowles, T. P. J., Silva, D. A., Shoultz, D., & Bernardes, G. J. L. (2023). De novo human angiotensin - converting enzyme 2 Decoy NL-CVX1 protects mice from severe disease after severe acute respiratory syndrome coronavirus 2 infection. The Journal of infectious diseases, 228(6), 723-733. https://doi.org/10.1093/infdis/jiad135

@article{2f6f41e6e404440cb3739285c22d0e6e,

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

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.",

keywords = "COVID-19, De novo protein decoys, K18-hACE2 mice, SARS-CoV-2, Treatment",

author = "Maria Rebelo and Cong Tang and Coelho, {Ana R.} and Carlos Lab{\~a}o-Almeida and Schneider, {Matthias M.} and Laurie Tatalick and Pedro Ruivo and Miranda, {Marta Pires de} and Andreia Gomes and T{\^a}nia Carvalho and Walker, {Matthew J.} and Hannes Ausserwoeger and Simas, {J. Pedro} and Marc Veldhoen and Knowles, {Tuomas P. J.} and Silva, {Daniel Adriano} and David Shoultz and Bernardes, {Gon{\c c}alo J. L.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.",

year = "2023",

month = sep,

day = "15",

doi = "10.1093/infdis/jiad135",

language = "English",

volume = "228",

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Rebelo, M, Tang, C, Coelho, AR, Labão-Almeida, C, Schneider, MM, Tatalick, L, Ruivo, P, Miranda, MPD, Gomes, A, Carvalho, T, Walker, MJ, Ausserwoeger, H, Simas, JP, Veldhoen, M, Knowles, TPJ, Silva, DA, Shoultz, D & Bernardes, GJL 2023, 'De novo human angiotensin - converting enzyme 2 Decoy NL-CVX1 protects mice from severe disease after severe acute respiratory syndrome coronavirus 2 infection', The Journal of infectious diseases, vol. 228, no. 6, pp. 723-733. https://doi.org/10.1093/infdis/jiad135

TY - JOUR

T1 - De novo human angiotensin - converting enzyme 2 Decoy NL-CVX1 protects mice from severe disease after severe acute respiratory syndrome coronavirus 2 infection

AU - Rebelo, Maria

AU - Tang, Cong

AU - Coelho, Ana R.

AU - Labão-Almeida, Carlos

AU - Schneider, Matthias M.

AU - Tatalick, Laurie

AU - Ruivo, Pedro

AU - Miranda, Marta Pires de

AU - Gomes, Andreia

AU - Carvalho, Tânia

AU - Walker, Matthew J.

AU - Ausserwoeger, Hannes

AU - Simas, J. Pedro

AU - Veldhoen, Marc

AU - Knowles, Tuomas P. J.

AU - Silva, Daniel Adriano

AU - Shoultz, David

AU - Bernardes, Gonçalo J. L.

PY - 2023/9/15

Y1 - 2023/9/15

N2 - 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.

AB - 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.

KW - COVID-19

KW - De novo protein decoys

KW - K18-hACE2 mice

KW - SARS-CoV-2

KW - Treatment

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U2 - 10.1093/infdis/jiad135

DO - 10.1093/infdis/jiad135

M3 - Article

C2 - 37279654

AN - SCOPUS:85171601438

SN - 0022-1899

VL - 228

SP - 723

EP - 733

JO - The Journal of infectious diseases

JF - The Journal of infectious diseases

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

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