Structure and function of SARS-CoV-2 polymerase.

Area of Science:

• Structural Biology
• Virology
• Molecular Biology

Background:

• Coronaviruses utilize RNA-dependent RNA polymerase (RdRp) for genome replication and expression.
• The replication-transcription complex (RTC), comprising RdRp and non-structural proteins (nsps), is crucial for viral RNA synthesis.
• Limited structural information on RdRp previously hindered understanding of coronavirus replication.

Purpose of the Study:

• To review available structural data of coronavirus RdRp.
• To elucidate the molecular mechanisms of viral polymerase function and interactions.
• To understand how antivirals inhibit coronavirus replication.

Main Methods:

• Cryo-electron microscopy (cryo-EM) for structural determination.
• Analysis of over twenty released SARS-CoV-2 polymerase structures.
• Integration of structural data with functional studies.

Main Results:

• Recent cryo-EM structures of SARS-CoV-1 and SARS-CoV-2 RdRp have become available.
• Structural data reveals interactions with accessory factors within the RTC.
• These structures provide insights into RNA synthesis, capping, and proofreading mechanisms.

Conclusions:

• Structural insights into coronavirus RdRp have rapidly advanced.
• Understanding RdRp structure and function is key to developing effective antivirals.
• The review highlights the molecular basis for inhibiting coronavirus replication.