The comprehensive SARS-CoV-2 ‘hijackome’ knowledge base
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Abstract
The continuous evolution of SARS-CoV-2 has led to the emergence of several variants of concern (VOCs) that significantly affect global health. This study aims to investigate how these VOCs affect host cells at proteome level to better understand the mechanisms of disease. To achieve this, we first analyzed the (phospho)proteome changes of host cells infected with Alpha, Beta, Delta, and Omicron BA.1 and BA.5 variants over time frames extending from 1 to 36 h post infection. Our results revealed distinct temporal patterns of protein expression across the VOCs, with notable differences in the (phospho)proteome dynamics that suggest variant-specific adaptations. Specifically, we observed enhanced expression and activation of key components within crucial cellular pathways such as the RHO GTPase cycle, RNA splicing, and endoplasmic reticulum-associated degradation (ERAD)-related processes. We further utilized proximity biotinylation mass spectrometry (BioID-MS) to investigate how specific mutation of these VOCs influence viral–host protein interactions. Our comprehensive interactomics dataset uncovers distinct interaction profiles for each variant, illustrating how specific mutations can change viral protein functionality. Overall, our extensive analysis provides a detailed proteomic profile of host cells for each variant, offering valuable insights into how specific mutations may influence viral protein functionality and impact therapeutic target identification. These insights are crucial for the potential use and design of new antiviral substances, aiming to enhance the efficacy of treatments against evolving SARS-CoV-2 variants.
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Spratt, A. N., Gallazzi, F., Quinn, T. P., Lorson, C. L., Sönnerborg, A. B., & Singh, K. D. (2021) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2021.1884224 · Cited by 50 · see citing works
Rusanen, J., Kareinen, L., Szirovicza, L., Uğurlu, H., Levanov, L., Jääskeläinen, A., Ahava, M. J., Kurkela, S., Saksela, K., Hedman, K., et al. (2021) · mBio · doi:10.1128/mbio.00902-21 · Cited by 47 · see citing works
The cryo-EM structure of an ERAD protein channel formed by tetrameric human Derlin-1
Rao, B., Li, S., Yao, D., Wang, Q., Xia, Y., Jia, Y., Shen, Y., & Cao, Y. (2021) · Science Advances · doi:10.1126/sciadv.abe8591 · Cited by 41 · see citing works
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Tabata, K., Arakawa, M., Ishida, K., Kobayashi, M., Nara, A., Sugimoto, T., Okada, T., Mori, K., & Morita, E. (2021) · Journal of Virology · doi:10.1128/jvi.02234-20 · Cited by 40 · see citing works
Tomás-Zuber, M., Mary, J., Lamour, F., Bur, D., & Lesslauer, W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m005822200 · Cited by 35 · see citing works
Interferon antagonists encoded by SARS-CoV-2 at a glance
Lee, J., Koepke, L., Kirchhoff, F., & Sparrer, K. M. J. (2022) · Medical Microbiology and Immunology · doi:10.1007/s00430-022-00734-9 · Cited by 35 · see citing works
Loving, K. A., Lin, A., & Cheng, A. C. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003741 · Cited by 35 · see citing works
CMGC Kinases in Health and Cancer
Chowdhury, I. M., Dashi, G., & Keskitalo, S. (2023) · Cancers · doi:10.3390/cancers15153838 · Cited by 32 · see citing works
Self-citationSARS-CoV-2 Incubation Period during the Omicron BA.5–Dominant Period in Japan
Ogata, T., & Tanaka, H. (2023) · Emerging infectious diseases · doi:10.3201/eid2903.221360 · Cited by 32 · see citing works
Wu, X., Manske, M. K., Ruan, G. J., Witter, T. L., Nowakowski, K. E., Abeykoon, J. P., Tang, X., Yu, Y., Gwin, K. A., Wu, A., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106929 · Cited by 29 · see citing works
The Role of Unfolded Protein Response in Coronavirus Infection and Its Implications for Drug Design
Xue, M., & Feng, L. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.808593 · Cited by 28 · see citing works
Liu, J.-F., Zhou, Y., Lu, S., Yang, Y.-H., Wu, S., Liu, D., Peng, X., & Yang, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00882-7 · Cited by 27 · see citing works
Evolution of PIKK family kinase inhibitors A new age cancer therapeutics
Kirubakaran, S. (2020) · Frontiers in bioscience · doi:10.2741/4866 · Cited by 26 · see citing works
The trans-Golgi SNARE syntaxin 10 is required for optimal development of Chlamydia trachomatis
Lucas, A. L., Ouellette, S. P., Kabeiseman, E. J., Cichos, K. H., & Rucks, E. A. (2015) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2015.00068 · Cited by 26 · see citing works
On the evolution of SARS-CoV-2 and the emergence of variants of concern
Magiorkinis, G. (2022) · Trends in Microbiology · doi:10.1016/j.tim.2022.10.008 · Cited by 25 · see citing works
Hunziker, A., Glas, I., Pohl, M. O., & Stertz, S. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110306 · Cited by 24 · see citing works
Ayinde, K. S., Pinheiro, G. M. S., & Ramos, C. H. I. (2022) · Biochimie · doi:10.1016/j.biochi.2022.05.016 · Cited by 24 · see citing works
Hou, W., Wang, S., Wu, H., Xue, L., Wang, B., Wang, S., & Wang, H. (2022) · Viruses · doi:10.3390/v14092044 · Cited by 22 · see citing works
Li, Z., Duan, P., Qiu, R., Fang, L., Fang, P., & Xiao, S. (2023) · Journal of Virology · doi:10.1128/jvi.00375-23 · Cited by 22 · see citing works
Belik, M., Liedes, O., Vara, S., Haveri, A., Pöysti, S., Kolehmainen, P., Maljanen, S., Huttunen, M., Reinholm, A., Lundberg, R., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1099246 · Cited by 21 · see citing works
Self-citationre3data.org (2015) · Registry of Research Repositories · doi:10.17616/r3q59f · Cited by 17 · see citing works
Eisa-Beygi, S., & Wen, X. (2014) · Antiviral Research · doi:10.1016/j.antiviral.2014.12.005 · Cited by 16 · see citing works
Live and let die: signaling AKTivation and UPRegulation dynamics in SARS-CoVs infection and cancer
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The C-terminus of PRK2/PKNγ is required for optimal activation by RhoA in a GTP-dependent manner
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Sampadi, B. K., Mullenders, L. H. F., & Vrieling, H. (2021) · Cells · doi:10.3390/cells10123407 · Cited by 10 · see citing works
Kolehmainen, P., Huttunen, M., Iakubovskaia, A., Maljanen, S., Tauriainen, S., Yatkin, E., Pasternack, A. H., Naves, R. A., Toivonen, L., Tähtinen, P. A., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-35471-3 · Cited by 9 · see citing works
Self-citationSarma, H., & Sastry, G. N. (2022) · ACS Omega · doi:10.1021/acsomega.2c03007 · Cited by 8 · see citing works
Kulkarni, P., & Padmanabhan, S. (2022) · Biotechnology Letters · doi:10.1007/s10529-022-03259-6 · Cited by 8 · see citing works
Mukherjee, A., Lo, M., Chandra, P., Chaudhuri, R. D., De, P., Dutta, S., & Chawla‐Sarkar, M. (2024) · Virology Journal · doi:10.1186/s12985-024-02460-5 · Cited by 7 · see citing works
Mishchenko, E. L., & Ivanisenko, V. A. (2022) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vjgb-22-15 · Cited by 5 · see citing works
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Netsey, E. K., Naandam, S. M., Asante, J., Kuukua, A. E., Yadem, A. C., Owusu, G., Shaffer, J. G., Srivastav, S. K., Doumbia, S., Owusu‐Dabo, E., et al. (2025) · JMIR Bioinformatics and Biotechnology · doi:10.2196/73637 · Cited by 7 · see citing works
Khaitov, M. R., Nikonova, A. A., Smirnov, V., Shilovsky, I. P., Кофиади, И. А., Ruzanova, E., Teplykh, V. A., Makarov, D., Vertichikh, A., Teplykh, S. V., et al. (2025) · Allergy · doi:10.1111/all.16515 · Cited by 5 · see citing works
Qing, C., Chen, H., Huang, S., Zhang, J., Zhou, C., Zhang, S., Luo, K., Wang, C., Hu, Z., Yang, Y., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-40957-x · Cited by 3 · see citing works
A Comprehensive Data Processing Pipeline for Phosphoproteomics in Viral Infection Studies
Huuskonen, S., Liu, X., Salokas, K., Tuhkala, A., Keskitalo, S., & Varjosalo, M. T. (2025) · Methods in molecular biology · doi:10.1007/978-1-0716-4502-4_15 · Cited by 2 · see citing works
Self-citationFradkin, T., & Schmidt‐Kastner, R. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1563040 · Cited by 1 · see citing works
Direct RNA sequencing reveals m6A modifications and isoform changes in SARS-CoV-2-infected HEK cells
Duru, I. C., Plavec, Z., Ylinen, A., Laine, P., James, M. J., Riihimäki, L., Butcher, S. J., Anastasina, M., & Auvinen, P. (2025) · Access Microbiology · doi:10.1099/acmi.0.001019.v3 · Cited by 1 · see citing works
Self-citationA system-wide investigation into the phosphoregulatory network of TNIK and its cellular implications
Sheela, A., Subair, S., Ummar, S., Mahin, A., Gopalakrishnan, A. P., Raju, R., & Soman, S. (2026) · Frontiers in Bioinformatics · doi:10.3389/fbinf.2026.1722876 · Cited by 1 · see citing works
Medarametla, P., Greenhalgh, J. C., Pöhner, I., Welch, M., Poso, A., Kronenberger, T., & Rahman, T. (2025) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c01120 · Cited by 1 · see citing works
Self-citationGrauvogel, L., Zollbrecht, E., Heymann, T., Brennsteiner, V., Pensl, C., Michaelis, A. C., & Mann, M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.03.729763 · Cited by 1 · see citing works
Skin as a Potential Entry Point for SARS-CoV-2 Virus
Trubetskoy, D., Grudzien, P. K., Chudakova, D. A., Kłopot, A., Shi, B., Bhalla, P., White, B. E. P., & Budunova, I. V. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27125382
Tyagi, S., Singh, A. K., Tyagi, N., Chaturvedi, R., & Kushwaha, H. R. (2026) · In Silico Research in Biomedicine · doi:10.1016/j.insi.2026.100477
Sathe, N. A., Morrell, E. D., Stanaway, I. B., Mabrey, F. L., Holton, S. E., Mikacenic, C. R., Anesi, G. L., Barnett, C. R., Brett‐Major, D. M., Broadhurst, M. J., et al. (2026) · Communications Medicine · doi:10.1038/s43856-026-01795-0
- Authors
- Huuskonen, S., Liu, X., Pöhner, I., Redchuk, T., Salokas, K., Lundberg, R., Maljanen, S., Belik, M., Reinholm, A., Kolehmainen, P., Tuhkala, A., Tripathi, G., Laine, P., Belanov, S., Auvinen, P., Vartiainen, M., Keskitalo, S., Österlund, P., Laine, L., Poso, A., Julkunen, I., Kakkola, L., & Varjosalo, M.
- Affiliations
- University of Helsinki (FI)
- University of Eastern Finland (FI)
- University of Turku (FI)
- Finnish Institute for Health and Welfare (FI)
- Corresponding author
- Varjosalo, Markku
- ORCID
- Huuskonen, Sini
- Liu, Xiaonan
- Pöhner, Ina
- Redchuk, Taras
- Salokas, Kari
- Lundberg, Rickard
- Maljanen, Sari
- Belik, Milja
- Reinholm, Arttu
- Kolehmainen, Pekka
- Tuhkala, Antti
- Tripathi, Garima
- Laine, Pia
- Belanov, Sergei
- Auvinen, Petri
- Vartiainen, Maria
- Keskitalo, Salla
- Österlund, Pamela
- Laine, Larissa
- Poso, Antti
- Julkunen, Ilkka
- Kakkola, Laura
- Varjosalo, Markku
- Venue
- Cell Discovery
- Published
- 2024-12-09
- Volume
- 10
- Issue
- 1
- Pages
- 125-125
- ISSN
- 2056-5968 (ISSN-L)
- PMC
- PMC11628605
- OpenAlex
- W4405182432
- Cited by
- 12
- References
- 117
- Citations by year
- 2026: 5 · 2025: 7
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Discovery (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UTUPub (University of Turku) (submittedVersion)
- UTUPub (University of Turku) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Työväentutkimus Vuosikirja (submittedVersion)
- Funders
- Academy of Finland (#336470)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- SARS-CoV-2, variants of concern, Omicron BA.1, Omicron BA.5, Delta variant, Alpha variant, host cell proteome, phosphoproteome, host-virus protein interaction, RNA splicing, ER-associated degradation, antiviral drug targets, host cell hijacking
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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