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SARS-CoV-2 N protein exerts antitumor effects in NSCLC by inducing DNA damage and augmenting chemotherapeutic

Xin Wang1, Fang Cao1, Di Chen1

  • 1Key Laboratory of Molecular Biology on Infectious Disease, Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Medical Oncology (Northwood, London, England)
|June 1, 2025
PubMed

Insights

The SARS-CoV-2 nucleocapsid protein enhances chemotherapy effectiveness against non-small cell lung cancer (NSCLC) by inducing DNA damage and suppressing tumor growth. This protein shows potential as a novel therapeutic agent for lung cancer.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • The SARS-CoV-2 nucleocapsid (N) protein has been implicated in cellular processes.
  • Previous research indicated the N protein can induce DNA damage via autophagic degradation of RNAi and splicing factors.

Purpose of the Study:

  • To investigate the synergistic effects of the SARS-CoV-2 N protein with chemotherapeutics in non-small cell lung cancer (NSCLC).
  • To explore the potential of the SARS-CoV-2 N protein as an antitumor agent for lung cancer.

Main Methods:

  • Utilized NSCLC cell lines to assess the combined effects of SARS-CoV-2 N protein and chemotherapeutics.
  • Investigated DNA damage induction and the cGAS-STING pathway activation.
  • Evaluated tumor cell proliferation and colony formation.
  • Tested the efficacy in a xenograft tumor mouse model with etoposide.

Main Results:

  • The SARS-CoV-2 N protein synergized with chemotherapeutics to induce DNA damage and activate the cGAS-STING pathway in NSCLC cells.
  • Combined treatment suppressed NSCLC cell proliferation and colony formation.
  • The SARS-CoV-2 N protein enhanced the antitumor effects of etoposide in vivo.

Conclusions:

  • The SARS-CoV-2 N protein exhibits a novel antitumor mechanism by potentiating chemotherapy effects in NSCLC.
  • The findings suggest the SARS-CoV-2 N protein could be a promising therapeutic candidate for lung cancer treatment.
Keywords:
COVID-19CancerDNA damageSARS-CoV-2 nucleocapsid proteincGAS-STING

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