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Updated: Oct 27, 2025

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Compartmentalization-aided interaction screening reveals extensive high-order complexes within the SARS-CoV-2

Weifan Xu1, Gaofeng Pei1, Hongrui Liu2

  • 1Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Beijing, China; Tsinghua-Peking Center for Life Sciences, Beijing, China; School of Life Sciences, Tsinghua University, Beijing, China.

Cell Reports
|July 23, 2021
PubMed
Summary

Researchers mapped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein interactions using a novel cell-based method. This reveals a complex network crucial for viral replication and potential therapeutic targets for COVID-19.

Keywords:
CoPICPRC2RTCSARS-CoV-2high-order complexesnonstructural proteinsprotein-protein interaction

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Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) relies on complex replication/transcription complexes (RTCs) for infection.
  • Understanding the interactions within these viral protein networks is crucial for developing effective treatments.

Purpose of the Study:

  • To develop and apply an innovative cell-based screening strategy, compartmentalization of protein-protein interactions in cells (CoPIC), to map the interaction network of SARS-CoV-2 RTC-related proteins.
  • To identify binary and ternary protein complexes involved in viral replication, transcription, and translation.

Main Methods:

  • Development of a novel cell-based interaction screening strategy named compartmentalization of protein-protein interactions in cells (CoPIC).
  • Application of CoPIC to screen and map interactions among 14 key viral proteins involved in SARS-CoV-2 replication and transcription.

Main Results:

  • Identification of 47 binary protein-protein interactions among 14 RTC-related viral proteins.
  • Discovery of extensive ternary complexes, suggesting the existence of higher-order protein structures within the RTC.
  • Demonstration of CoPIC as an efficient and robust method for screening protein interactions in situ.

Conclusions:

  • The study presents an effective CoPIC strategy for dissecting viral protein interaction networks.
  • A complex interaction network among SARS-CoV-2 RTC factors has been elucidated.
  • These findings offer new avenues for understanding SARS-CoV-2 biology and designing therapeutic interventions against COVID-19.