Evidence map›Paper›PMID 34709727›Full record

ArticleMolecular systems biology2021

SARS-CoV-2-host proteome interactions for antiviral drug discovery.

Xiaonan Liu, Sini Huuskonen, Tuomo Laitinen, Taras Redchuk, Mariia Bogacheva, Kari Salokas, Ina Pöhner, Tiina Öhman, Arun Kumar Tonduru, Antti Hassinen and 6 more

Abstract read
In one paragraph

Article in Molecular systems biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing 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

71 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Impact of nutrition on long COVID.Sports medicine and health science · 2026
    Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. The main protease (MCommunications biology · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. The peptidoglycan ofScience translational medicine · 2025
    Article
  16. Review
  17. Article
  18. Article
  19. Unlocking TRPM7 interactions: A database-driven quest.Computational and structural biotechnology journal · 2025
    Review
  20. Article

11 more citing papers are in PubMed but not listed here.

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

16 authors.

Xiaonan LiuInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-9600-0536
Sini HuuskonenInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.ORCID 0000-0003-3857-1805
Tuomo Laitinen *School of Pharmacy, University of Eastern Finland, Kuopio, Finland.ORCID 0000-0003-1539-2142
Taras Redchuk *Institute of Biotechnology, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-6724-9025
Mariia Bogacheva *Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.ORCID 0000-0001-6608-1120
Kari SalokasInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-4471-6698
Ina PöhnerSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland.ORCID 0000-0002-2801-8902
Tiina ÖhmanInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.ORCID 0000-0001-6647-8873
Arun Kumar TonduruSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland.ORCID 0000-0001-6986-4198
Antti HassinenHelsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.ORCID 0000-0001-9491-2868
Lisa GawriyskiInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-1950-4749
Salla KeskitaloInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.ORCID 0000-0001-5555-1975
Maria K VartiainenInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-2017-0475
Vilja PietiäinenHelsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.ORCID 0000-0003-3125-2406
Antti PosoSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland.ORCID 0000-0003-4196-4204
Markku VarjosaloInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-1340-9732

Funding

Academy of Finland (Suomen Akatemia) 288487Academy of Finland (Suomen Akatemia) 336470
6 · The paper itself

Abstract

Treatment options for COVID-19, caused by SARS-CoV-2, remain limited. Understanding viral pathogenesis at the molecular level is critical to develop effective therapy. Some recent studies have explored SARS-CoV-2-host interactomes and provided great resources for understanding viral replication. However, host proteins that functionally associate with SARS-CoV-2 are localized in the corresponding subnetwork within the comprehensive human interactome. Therefore, constructing a downstream network including all potential viral receptors, host cell proteases, and cofactors is necessary and should be used as an additional criterion for the validation of critical host machineries used for viral processing. This study applied both affinity purification mass spectrometry (AP-MS) and the complementary proximity-based labeling MS method (BioID-MS) on 29 viral ORFs and 18 host proteins with potential roles in viral replication to map the interactions relevant to viral processing. The analysis yields a list of 693 hub proteins sharing interactions with both viral baits and host baits and revealed their biological significance for SARS-CoV-2. Those hub proteins then served as a rational resource for drug repurposing via a virtual screening approach. The overall process resulted in the suggested repurposing of 59 compounds for 15 protein targets. Furthermore, antiviral effects of some candidate drugs were observed in vitro validation using image-based drug screen with infectious SARS-CoV-2. In addition, our results suggest that the antiviral activity of methotrexate could be associated with its inhibitory effect on specific protein-protein interactions.

Indexed as

COVID-19 Drug TreatmentDrug DiscoveryAntiviral AgentsCOVID-19Drug RepositioningHost-Pathogen InteractionsHumansMass SpectrometryMethotrexateProteomeProteomicsSARS-CoV-2Virus ReplicationAntiviral AgentsMethotrexateProteomedrug discoverymass spectrometryproteomicsSARS-CoV-2virus-host interactions

Identifiers

PMID34709727
PMCPMC8552907

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.