Recent advances in functional studies of coronavirus NSP13 helicase and challenges in inhibitor development

Coronavirus helicase NSP13 is essential for viral replication and transcription and is a promising target for broad-spectrum anti-coronavirus drugs due to its high sequence conservation and structural homology. This review summarizes NSP13 sequence features, structural organization, and functional activities across the seven human-infecting coronaviruses. We outline key enzymatic properties, including duplex RNA/DNA unwinding and NTP hydrolysis, and describe how NSP13 cooperates with other nonstructural proteins to drive replication and transcription. Beyond canonical helicase roles, we discuss the genomic distribution of G-quadruplex (G4) elements in coronaviruses and potential functional connections between G4 structures and NSP13 in regulating the viral life cycle. Finally, we highlight recent progress in developing NSP13-targeting inhibitors and consider their potential utility against COVID-19 and other emerging coronaviruses, providing a rationale for broad-spectrum antiviral design.