Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design.
Nat Rev Mol Cell Biol
; 23(1): 21-39, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-1537322
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Transcription, Genetic
/
Virus Replication
/
Drug Design
/
SARS-CoV-2
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Nat Rev Mol Cell Biol
Journal subject:
Molecular Biology
Year:
2022
Document Type:
Article
Affiliation country:
S41580-021-00432-z
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