{
  "abstract": "Middle East Respiratory Syndrome Coronavirus (MERS-CoV) poses a significant public health threat, with a fatality rate of 37% and no approved therapeutics. Non-structural protein 10 (nsp10) is an essential cofactor that activates both the nsp14 3'-5' exoribonuclease (ExoN) activity required for RNA proofreading and the nsp16 2'-O-methyltransferase (2'-O-MTase) implicated in viral RNA cap formation. Despite its functional importance, the unbound structure and dynamics of MERS-CoV nsp10 in solution remain uncharacterised. Here we report a near-complete NMR backbone and sidechain assignment and characterise the solution structure and dynamics of the protein by NMR. In contrast to the folded 1 helix observed in crystal structures of coronavirus nsp10, we find that this region is intrinsically disordered in solution, with residues 10-22 undetectable under standard conditions and further evidenced by pH titration, temperature-dependent NMR, and CLEANEX-PM experiments. Analysis of NOE contacts confirmed that the core adopts the conserved coronavirus nsp10 fold, consistent with the AlphaFold-predicted structure. 15N backbone relaxation measurements indicated a rigid, well-ordered core with only localised flexibility, despite a relatively low proportion of secondary structure elements, and CPMG and CEST experiments detected no conformational exchange on the s-ms timescale. Building on this structural and dynamic characterisation, we explored the ligandability of nsp10 by 19F NMR fragment screening. Screening of a 463-compound library identified 23 initial hits (4.97% hit rate), of which 20 were confirmed by 15N SOFAST-HMQC and eight gave quantifiable affinities by MST (Kd 0.5-6.9 mM), the remainder being too weak for reliable determination. Chemical shift perturbations clustered near functional surfaces of the folded core, indicating that MERS-CoV nsp10 is ligandable and providing chemical starting points for antiviral development.",
  "abstract_shown": true,
  "affiliations": [
    "University College London"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "D. Dong"
    },
    {
      "name": "F. G. Kozielski"
    },
    {
      "affs": [
        0
      ],
      "name": "C. A. Waudby"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bevkw6xnhkm60.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.754126",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754126v1.full",
  "id": "bevkw6xnhkm60",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754126v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7214199602",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754126v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bevkw6xnhkm60.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:26Z",
      "native_id": "10.64898/2026.09.24.754126",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754126v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Solution structure, dynamics and fragment binding of unbound MERS-CoV nsp10",
  "title_text": "Solution structure, dynamics and fragment binding of unbound MERS-CoV nsp10",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:26Z",
  "url": "https://research.draconitic.com/paper/bevkw6xnhkm60",
  "venue": "bioRxiv",
  "versions": []
}