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The Life of SARS-CoV-2 Inside Cells: Replication-Transcription Complex Assembly and Function
Zhiyong Lou1, Zihe Rao1,2,3,4,5,6
1Ministry of Education Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China; email: louzy@mail.tsinghua.edu.cn, raozh@tsinghua.edu.cn.
Abstract:
The persistence of the coronavirus disease 2019 (COVID-19) pandemic has resulted in increasingly disruptive impacts, and it has become the most devastating challenge to global health in a century. The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants challenges the currently available therapeutics for clinical application. Nonstructural proteins (also known as replicase proteins) with versatile biological functions play central roles in viral replication and transcription inside the host cells, and they are the most conserved target proteins among the SARS-CoV-2 variants. Specifically, they constitute the replication-transcription complexes (RTCs) dominating the synthesis of viral RNA. Knowledge of themolecular mechanisms of nonstructural proteins and their assembly into RTCs will benefit the development of antivirals targeting them against existing or potentially emerging variants. In this review, we summarize current knowledge of the structures and functions of coronavirus nonstructural proteins as well as the assembly and functions of RTCs in the life cycle of the virus.
Insights
This review details coronavirus nonstructural proteins and replication-transcription complexes (RTCs). Understanding these conserved viral targets is key to developing new antivirals against COVID-19 variants.
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- The COVID-19 pandemic remains a significant global health challenge.
- Emerging SARS-CoV-2 variants pose a threat to existing therapeutics.
- Nonstructural proteins are crucial for viral RNA synthesis and are conserved across variants.
Purpose of the Study:
- To review the structures and functions of coronavirus nonstructural proteins.
- To elucidate the assembly and functions of replication-transcription complexes (RTCs).
- To highlight the potential of nonstructural proteins as targets for novel antiviral development.
Main Methods:
- Literature review of structural and functional studies on coronavirus nonstructural proteins.
- Analysis of research on the assembly and mechanisms of RTCs.
- Synthesis of current knowledge on viral replication and transcription processes.
Main Results:
- Nonstructural proteins form the core of RTCs, essential for viral RNA replication.
- These proteins exhibit conserved structures and functions across SARS-CoV-2 variants.
- Understanding their molecular mechanisms provides insights into viral pathogenesis.
Conclusions:
- Nonstructural proteins and RTCs are critical and conserved targets for antiviral strategies.
- Targeting these components can lead to broad-spectrum antivirals effective against current and future variants.
- Further research into these viral machinery components is vital for pandemic preparedness.
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