Identification and Characterization of a Novel Protein-Protein Interaction Among SARS-CoV-2 Nucleocapsid, Host SFPQ, and hnRNP U and Its Potential Role in Virus Replication.

Agrahari, A. and Archana, K. and Singh, N. and Haldar, S. and Thakur, Krishan Gopal and Vinod, B.S.V and Tripathi, Rajkumar (2025) Identification and Characterization of a Novel Protein-Protein Interaction Among SARS-CoV-2 Nucleocapsid, Host SFPQ, and hnRNP U and Its Potential Role in Virus Replication. Biology of the cell,, 117 (4).

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Official URL: https://pubmed.ncbi.nlm.nih.gov/40259455/

Abstract

SARS-CoV-2 has led to significant global health and economic challenges and caused the COVID-19 pandemic. The ability of the virus to replicate adeptly within host cells is critical for its pathogenicity. The structural nucleocapsid (N) protein of SARS-CoV-2 packages newly synthesized viral RNA with the association of various host proteins that may contribute to different functions in maintaining a productive viral life cycle. In this study, we report the identification and characterization of host proteins SFPQ and hnRNP U interacting with SARS-CoV-2 N protein in both N-transfected cells and virus-infected cells, forming a hetero-trimeric protein complex. Using carefully designed peptides that span the length of N protein and competitive inhibition, we identified the interacting domains at N protein that interact with SFPQ and hnRNP U. Our results constitute the first report that the characterized N protein and host SFPQ and hnRNP U form a hetero-trimeric protein complex in both N transfected cells and virus-infected cells. Utilizing competitive peptides, we were able to disrupt the hetero-trimeric protein complex in virus-infected cells, leading to reduction in viral replication. These results clearly demonstrate that N-SFPQ-hnRNP U hetero-trimeric protein complex formation is found in SARS-CoV-2 infected cells that regulate viral replication. Our findings suggest that the protein-protein interaction (PPI) between N-SFPQ-hnRNP U hetero-trimeric protein complexes could be a novel drug target for developing therapeutics against COVID-19.

Item Type: Article
Additional Information: Copyright of this article belongs to Wiley
Uncontrolled Keywords: COVID‐19; SARS‐CoV‐2; SFPQ; hnRNP U; nucleocapsid
Subjects: Q Science > QR Microbiology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 31 Jan 2026 14:25
Last Modified: 31 Jan 2026 14:27
URI: http://crdd.osdd.net/open/id/eprint/3194

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