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- EMDB-46957: Designed miniproteins potently inhibit and protect against MERS_C... -

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Basic information

Entry
Database: EMDB / ID: EMD-46957
TitleDesigned miniproteins potently inhibit and protect against MERS_CoV. MERS-CoV S in complex with cb3_GGGSGGGS_SB175B175, linker 7(Global refinement after focused classification)
Map dataMain map
Sample
  • Complex: Designed miniproteins potently inhibit and protect against MERS_CoV. MERS-CoV S in complex with cb3_GGGSGGGS_SB175B175, linker 7(Global refinement after focused classification)
    • Protein or peptide: Designed miniproteins potently inhibit and protect against MERS_CoV. MERS-CoV S in complex with cb3_GGGSGGGS_SB175B175, linker 7(Global refinement after focused classification)
KeywordsCoronavirus / betacoronavirus / MERS-CoV / single particle cryo-EM / neutralization assays / binding assays / miniproteins inhibitors / fusion assays / in vivo protection / VIRAL PROTEIN
Biological speciesMiddle East respiratory syndrome-related coronavirus
Methodsingle particle reconstruction / cryo EM / Resolution: 3.0 Å
AuthorsTortorici MA / Veesler D
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI158186 United States
CitationJournal: Cell Rep / Year: 2025
Title: Designed miniproteins potently inhibit and protect against MERS-CoV.
Authors: Robert J Ragotte / M Alejandra Tortorici / Nicholas J Catanzaro / Amin Addetia / Brian Coventry / Heather M Froggatt / Jimin Lee / Cameron Stewart / Jack T Brown / Inna Goreshnik / Jeremiah ...Authors: Robert J Ragotte / M Alejandra Tortorici / Nicholas J Catanzaro / Amin Addetia / Brian Coventry / Heather M Froggatt / Jimin Lee / Cameron Stewart / Jack T Brown / Inna Goreshnik / Jeremiah N Sims / Lukas F Milles / Basile I M Wicky / Matthias Glögl / Stacey Gerben / Alex Kang / Asim K Bera / William Sharkey / Alexandra Schäfer / Jack R Harkema / Ralph S Baric / David Baker / David Veesler /
Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen with a 36% case-fatality rate in humans. No vaccines or specific therapeutics are currently approved for use in humans ...Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen with a 36% case-fatality rate in humans. No vaccines or specific therapeutics are currently approved for use in humans or the camel host reservoir. Here, we computationally designed monomeric and homo-oligomeric miniproteins that bind with high affinity to the MERS-CoV spike (S) glycoprotein, the main target of neutralizing antibodies and vaccine development. We show that these miniproteins broadly neutralize a panel of MERS-CoV S variants, spanning the known antigenic diversity of this pathogen, by targeting a conserved site in the receptor-binding domain (RBD). The miniproteins directly compete with binding of the dipeptidylpeptidase 4 (DPP4) receptor to MERS-CoV S, thereby blocking viral attachment to the host entry receptor and subsequent membrane fusion. Intranasal administration of a lead miniprotein provides prophylactic protection against stringent MERS-CoV challenge in mice, motivating its future clinical development as a next-generation countermeasure against this virus with pandemic potential.
History
DepositionSep 8, 2024-
Header (metadata) releaseAug 13, 2025-
Map releaseAug 13, 2025-
UpdateFeb 25, 2026-
Current statusFeb 25, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_46957.png

Downloads & links

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Map

FileDownload / File: emd_46957.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationMain map
Projections & slices

Image control

Size
Brightness
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
1 Å/pix.
x 512 pix.
= 512. Å		1 Å/pix.
x 512 pix.
= 512. Å		1 Å/pix.
x 512 pix.
= 512. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.217
Minimum - Maximum-1.6416061 - 3.0749714
Average (Standard dev.)-0.00013391601 (±0.047400463)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 512.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: Unsharpened map

Fileemd_46957_additional_1.map
AnnotationUnsharpened map
Projections & Slices
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Half map: Half map A

Fileemd_46957_half_map_1.map
AnnotationHalf map A
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Histogram

Histogram (log scale)

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Half map: Half map B

Fileemd_46957_half_map_2.map
AnnotationHalf map B
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Sample components

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Entire : Designed miniproteins potently inhibit and protect against MERS_C...

EntireName: Designed miniproteins potently inhibit and protect against MERS_CoV. MERS-CoV S in complex with cb3_GGGSGGGS_SB175B175, linker 7(Global refinement after focused classification)
Components
  • Complex: Designed miniproteins potently inhibit and protect against MERS_CoV. MERS-CoV S in complex with cb3_GGGSGGGS_SB175B175, linker 7(Global refinement after focused classification)
    • Protein or peptide: Designed miniproteins potently inhibit and protect against MERS_CoV. MERS-CoV S in complex with cb3_GGGSGGGS_SB175B175, linker 7(Global refinement after focused classification)

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Supramolecule #1: Designed miniproteins potently inhibit and protect against MERS_C...

SupramoleculeName: Designed miniproteins potently inhibit and protect against MERS_CoV. MERS-CoV S in complex with cb3_GGGSGGGS_SB175B175, linker 7(Global refinement after focused classification)
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Middle East respiratory syndrome-related coronavirus

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Macromolecule #1: Designed miniproteins potently inhibit and protect against MERS_C...

MacromoleculeName: Designed miniproteins potently inhibit and protect against MERS_CoV. MERS-CoV S in complex with cb3_GGGSGGGS_SB175B175, linker 7(Global refinement after focused classification)
type: protein_or_peptide / ID: 1 / Enantiomer: LEVO
SequenceString: MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTVDVGPDSV KSACIEVDIQ QTFFDKTWPR PIDVSKADGI IYPQGRTYSN ITITYQGLFP YQGDHGDMYV YSAGHATGTT PQKLFVANYS QDVKQFANGF VVRIGAAANS TGTVIISPST SATIRKIYPA FMLGSSVGNF ...String:
MGILPSPGMP ALLSLVSLLS VLLMGCVAET GTVDVGPDSV KSACIEVDIQ QTFFDKTWPR PIDVSKADGI IYPQGRTYSN ITITYQGLFP YQGDHGDMYV YSAGHATGTT PQKLFVANYS QDVKQFANGF VVRIGAAANS TGTVIISPST SATIRKIYPA FMLGSSVGNF SDGKMGRFFN HTLVLLPDGC GTLLRAFYCI LEPRSGNHCP AGNSYTSFAT YHTPATDCSD GNYNRNASLN SFKEYFNLRN CTFMYTYNIT EDEILEWFGI TQTAQGVHLF SSRYVDLYGG NMFQFATLPV YDTIKYYSII PHSIRSIQSD RKAWAAFYVY KLQPLTFLLD FSVDGYIRRA IDCGFNDLSQ LHCSYESFDV ESGVYSVSSF EAKPSGSVVE QAEGVECDFS PLLSGTPPQV YNFKRLVFTN CNYNLTKLLS LFSVNDFTCS QISPAAIASN CYSSLILDYF SYPLSMKSDL SVSSAGPISQ FNYKQSFSNP TCLILATVPH NLTTITKPLK YSYINKCSRL LSDDRTEVPQ LVNANQYSPC VSIVPSTVWE DGDYYRKQLS PLEGGGWLVA SGSTVAMTEQ LQMGFGITVQ YGTDTNSVCP KLEFANDTKI ASQLGNCVEY SLYGVSGRGV FQNCTAVGVR QQRFVYDAYQ NLVGYYSDDG NYYCLRACVS VPVSVIYDKE TKTHATLFGS VACEHISSTM SQYSRSTRSM LKRRDSTYGP LQTPVGCVLG LVNSSLFVED CKLPLGQSLC ALPDTPSTLT PASVGSVPGE MRLASIAFNH PIQVDQLNSS YFKLSIPTNF SFGVTQEYIQ TTIQKVTVDC KQYVCNGFQK CEQLLREYGQ FCSKINQALH GANLRQDDSV RNLFASVKSS QSSPIIPGFG GDFNLTLLEP VSISTGSRSA RSAIEDLLFD KVTIADPGYM QGYDDCMQQG PASARDLICA QYVAGYKVLP PLMDVNMEAA YTSSLLGSIA GVGWTAGLSS FAAIPFAQSI FYRLNGVGIT QQVLSENQKL IANKFNQALG AMQTGFTTTN EAFQKVQDAV NNNAQALSKL ASELSNTFGA ISASIGDIIQ RLDPPEQDAQ IDRLINGRLT TLNAFVAQQL VRSESAALSA QLAKDKVNEC VKAQSKRSGF CGQGTHIVSF VVNAPNGLYF MHVGYYPSNH IEVVSAYGLC DAANPTNCIA PVNGYFIKTN NTRIVDEWSY TGSSFYAPEP ITSLNTKYVA PQVTYQNIST NLPPPLLGNS TGIDFQDELD EFFKNVSTSI PNFGSLTQIN TTLLDLTYEM LSLQQVVKAL NESYIDLKEL GNYTYYNKGS GYIPEAPRDG QAYVRKDGEW VLLSTFLGGS GLNDIFEAQK IEWHEGGSHH HHHHHH

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 63523
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING

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