Evidence map›Paper›PMID 35128408›Full record

ArticleRSC chemical biology2022

Identification of fragments binding to SARS-CoV-2 nsp10 reveals ligand-binding sites in conserved interfaces between nsp10 and nsp14/nsp16.

Frank Kozielski, Céleste Sele, Vladimir O Talibov, Jiaqi Lou, Danni Dong, Qian Wang, Xinyue Shi, Maria Nyblom, Annika Rogstam, Tobias Krojer and 2 more

Abstract read
In one paragraph

Article in RSC chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

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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.

Frank KozielskiSchool of Pharmacy, University College London 29-39 Brunswick Square London WC1N 1AX UK.
Céleste SeleDepartment of Biology & Lund Protein Production Platform, Lund University Sölvegatan 35 22362 Lund Sweden wolfgang.knecht@biol.lu.se +46 46 2227785.
Vladimir O TalibovBioMAX beamline, MAX IV Laboratory Fotongatan 2 22484 Lund Sweden.
Jiaqi LouSchool of Pharmacy, University College London 29-39 Brunswick Square London WC1N 1AX UK.
Danni DongSchool of Pharmacy, University College London 29-39 Brunswick Square London WC1N 1AX UK.
Qian WangSchool of Pharmacy, University College London 29-39 Brunswick Square London WC1N 1AX UK.
Xinyue ShiSchool of Pharmacy, University College London 29-39 Brunswick Square London WC1N 1AX UK.
Maria NyblomDepartment of Biology & Lund Protein Production Platform, Lund University Sölvegatan 35 22362 Lund Sweden wolfgang.knecht@biol.lu.se +46 46 2227785.
Annika RogstamDepartment of Biology & Lund Protein Production Platform, Lund University Sölvegatan 35 22362 Lund Sweden wolfgang.knecht@biol.lu.se +46 46 2227785.
Tobias KrojerBioMAX beamline, MAX IV Laboratory Fotongatan 2 22484 Lund Sweden.
Zoë FisherDepartment of Biology & Lund Protein Production Platform, Lund University Sölvegatan 35 22362 Lund Sweden wolfgang.knecht@biol.lu.se +46 46 2227785.ORCID https://orcid.org/0000-0001-8287-0269
Wolfgang KnechtDepartment of Biology & Lund Protein Production Platform, Lund University Sölvegatan 35 22362 Lund Sweden wolfgang.knecht@biol.lu.se +46 46 2227785.ORCID https://orcid.org/0000-0001-9530-7598

Funding

Medical Research Council MC_PC_19054
6 · The paper itself

Abstract

Since the emergence of SARS-CoV-2 in 2019, Covid-19 has developed into a serious threat to our health, social and economic systems. Although vaccines have been developed in a tour-de-force and are now increasingly available, repurposing of existing drugs has been less successful. There is a clear need to develop new drugs against SARS-CoV-2 that can also be used against future coronavirus infections. Non-structural protein 10 (nsp10) is a conserved stimulator of two enzymes crucial for viral replication, nsp14 and nsp16, exhibiting exoribonuclease and methyltransferase activities. Interfering with RNA proofreading or RNA cap formation represents intervention strategies to inhibit replication. We applied fragment-based screening using nano differential scanning fluorometry and X-ray crystallography to identify ligands targeting SARS-CoV-2 nsp10. We identified four fragments located in two distinct sites: one can be modelled to where it would be located in the nsp14-nsp10 complex interface and the other in the nsp16-nsp10 complex interface. Microscale thermophoresis (MST) experiments were used to quantify fragment affinities for nsp10. Additionally, we showed by MST that the interaction by nsp14 and 10 is weak and thereby that complex formation could be disrupted by small molecules. The fragments will serve as starting points for the development of more potent analogues using fragment growing techniques and structure-based drug design.

Identifiers

PMID35128408
PMCPMC8729259

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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.