@article{fdi:010086727,
  title = {{B}iosynthetic proteins targeting the {SARS}-{C}o{V}-2 spike as anti-virals},
  author = {{T}hebault, {S}. and {L}ejal, {N}. and {D}ogliani, {A}. and {D}onchet, {A}. and {U}rvoas, {A}. and {V}alerio-{L}epiniec, {M}. and {L}avie, {M}. and {B}aronti, {C}{\'e}cile and {T}ouret, {F}. and {D}a {C}osta, {B}. and {B}ourgon, {C}. and {F}raysse, {A}. and {S}aint-{A}lbin-{D}eliot, {A}. and {M}orel, {J}. and {K}lonjkowski, {B}. and {L}amballerie, {X}. de and {D}ubuisson, {J}. and {R}oussel, {A}. and {M}inard, {P}. and {L}e {P}oder, {S}. and {M}eunier, {N}. and {D}elmas, {B}.},
  editor = {},
  language = {{ENG}},
  abstract = {{T}he binding of the {SARS}-{C}o{V}-2 spike to angiotensin-converting enzyme 2 ({ACE}2) promotes virus entry into the cell. {T}argeting this interaction represents a promising strategy to generate antivirals. {B}y screening a phage-display library of biosynthetic protein sequences build on a rigid alpha-helicoidal {HEAT}-like scaffold (named a{R}eps), we selected candidates recognizing the spike receptor binding domain ({RBD}). {T}wo of them ({F}9 and {C}2) bind the {RBD} with affinities in the n{M} range, displaying neutralisation activity in vitro and recognizing distinct sites, {F}9 overlapping the {ACE}2 binding motif. {T}he {F}9-{C}2 fusion protein and a trivalent alpha {R}ep form ({C}2-foldon) display 0.1 n{M} affinities and {EC}50 of 8-18 n{M} for neutralization of {SARS}-{C}o{V}-2. {I}n hamsters, {F}9-{C}2 instillation in the nasal cavity before or during infections effectively reduced the replication of a {SARS}-{C}o{V}-2 strain harbouring the {D}614{G} mutation in the nasal epithelium. {F}urthermore, {F}9-{C}2 and/or {C}2-foldon effectively neutralized {SARS}-{C}o{V}-2 variants (including delta and omicron variants) with {EC}50 values ranging from 13 to 32 n{M}. {W}ith their high stability and their high potency against {SARS}-{C}o{V}-2 variants, alpha {R}eps provide a promising tool for {SARS}-{C}o{V}-2 therapeutics to target the nasal cavity and mitigate virus dissemination in the proximal environment.},
  keywords = {},
  booktitle = {},
  journal = {{PL}o{S} {P}athogens},
  volume = {18},
  numero = {9},
  pages = {e1010799 [21 p.]},
  ISSN = {1553-7366},
  year = {2022},
  DOI = {10.1371/journal.ppat.1010799},
  URL = {https://www.documentation.ird.fr/hor/fdi:010086727},
}