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Updated: Oct 12, 2025

Production of a SARS-CoV-2 Virus-Like-Particle System to Investigate Viral Life Cycles In Vitro
Published on: June 6, 2025
Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug
Brandon Malone1, Nadya Urakova2, Eric J Snijder3
1Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY, USA.
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed millions of people and continues to cause massive global upheaval. Coronaviruses are positive-strand RNA viruses with an unusually large genome of ~30 kb. They express an RNA-dependent RNA polymerase and a cohort of other replication enzymes and supporting factors to transcribe and replicate their genomes. The proteins performing these essential processes are prime antiviral drug targets, but drug discovery is hindered by our incomplete understanding of coronavirus RNA synthesis and processing. In infected cells, the RNA-dependent RNA polymerase must coordinate with other viral and host factors to produce both viral mRNAs and new genomes. Recent research aiming to decipher and contextualize the structures, functions and interplay of the subunits of the SARS-CoV-2 replication and transcription complex proteins has burgeoned. In this Review, we discuss recent advancements in our understanding of the molecular basis and complexity of the coronavirus RNA-synthesizing machinery. Specifically, we outline the mechanisms and regulation of RNA translation, replication and transcription. We also discuss the composition of the replication and transcription complexes and their suitability as targets for antiviral therapy.
Insights
Understanding SARS-CoV-2 RNA synthesis is crucial for developing new antiviral drugs. This review details the molecular mechanisms and protein complexes involved in coronavirus RNA replication and transcription.
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant global health threat.
- Coronaviruses are positive-strand RNA viruses with large genomes requiring complex replication machinery.
- Incomplete understanding of coronavirus RNA synthesis impedes antiviral drug development.
Purpose of the Study:
- To review recent advancements in understanding the SARS-CoV-2 RNA replication and transcription complex.
- To elucidate the molecular mechanisms and regulation of viral RNA synthesis.
- To assess the suitability of these complexes as antiviral drug targets.
Main Methods:
- Review of current scientific literature on coronavirus RNA synthesis.
- Analysis of structural and functional studies of replication and transcription complex proteins.
- Discussion of viral RNA translation, replication, and transcription mechanisms.
Main Results:
- Significant progress has been made in deciphering the structures and functions of SARS-CoV-2 replication proteins.
- The interplay between viral and host factors in RNA synthesis is becoming clearer.
- Key enzymes and supporting factors have been identified as potential drug targets.
Conclusions:
- A deeper understanding of the coronavirus RNA synthesizing machinery is essential for effective antiviral therapies.
- Targeting the replication and transcription complexes offers a promising strategy for new drug discovery.
- Further research into the molecular basis of RNA synthesis will accelerate the development of novel therapeutics.
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