Evidence map›Paper›PMID 41659447›Full record

ArticlebioRxiv : the preprint server for biology2026

Mapping SARS-CoV-2 Nucleocapsid Function with Nanobodies.

Jules B Reyes-Weinstein, Timothy A Bates, Aidan Anastas, Ayna Alfahdli, Mila Trank-Green, Savannah K McBride, Michelle Garcia, Matthew A H Parson, Meredith L Jenkins, John E Burke and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Jules B Reyes-WeinsteinDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.ORCID 0000-0002-2983-3386
Timothy A BatesDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.ORCID 0000-0002-2533-7668
Aidan AnastasDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.ORCID 0009-0005-3875-1162
Ayna AlfahdliDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.
Mila Trank-GreenDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.ORCID 0009-0000-4934-3811
Savannah K McBrideDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.ORCID 0000-0001-8585-8038
Michelle GarciaDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.
Matthew A H ParsonDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Meredith L JenkinsDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
John E BurkeDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.ORCID 0000-0001-7904-9859
Eric BarklisDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.ORCID 0000-0003-4944-6671
Fikadu G TafesseDepartment of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.ORCID 0000-0002-8575-4164

Funding

HIV-1 Gag Precursor Protein InteractionsR01AI152579 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI BARKLIS, ERIC W · 2020 to 2024
$2.5M
Determining the role of sphingolipids in Mycobacterium tuberculosis infectionR01AI141549 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI TAFESSE, FIKADU G. · 2020 to 2025
$2.4M
Interdisciplinary Training in Microbial Pathogenesis and ImmunologyT32AI170496 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI Patrizia Caposio, Scott M Landfear · 2023 to 2026
$1.5M
Octet Red384S10OD023413 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI BARR-GILLESPIE, PETER GORDON · 2017 to 2017
$318k
NIAID NIH HHS R01 AI141549NIAID NIH HHS R01 AI152579NIAID NIH HHS T32 AI170496NIH HHS S10 OD023413
6 · The paper itself

Abstract

The SARS-CoV-2 nucleocapsid (N) protein is essential for viral RNA packaging, replication, and immune modulation. Despite its central role, the mechanistic contributions of its individual domains, the N-terminal domain (NTD), C-terminal domain (CTD), and the intrinsically flexible linker (LINK), remain poorly defined, largely due to the protein's structural complexity. In this study, we developed a panel of twelve alpaca-derived nanobodies (VHHs) targeting the NTD, CTD, and LINK regions of N. Using ELISA and biolayer interferometry, we characterized their binding affinities, and we mapped their epitopes via hydrogen-deuterium exchange-mass spectrometry (HDX-MS) and structural modeling. When expressed intracellularly, these VHHs inhibited SARS-CoV-2 infection. In vitro, they disrupted phase separation of the N protein, a critical step in viral replication. Strikingly, VHHs targeting each domain independently blocked both phase condensation and viral replication, underscoring the functional importance of all three regions. These findings establish domain-specific VHHs as versatile tools for dissecting N biology, with promising therapeutic potential.

Identifiers

PMID41659447
PMCPMC12873808

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.