The regulatory mechanisms of SARS-CoV-2 N protein helicase and its annealing activity.

Publication date: Dec 19, 2025

The nucleocapsid (N) protein of SARS-CoV-2 performs multiple functions essential for viral replication and host adaptation. Here, we identify ionic strength as a critical determinant of its dual nucleic acid-manipulating activities. Under low-salt conditions (≤100 mM NaCl), SARS-CoV-2 N primarily promotes strand annealing, whereas at high ionic strength (≥300 mM NaCl), its helicase activity is additively enhanced. SARS-CoV-2 N also preferentially acts on DNA rather than RNA substrates and modulates the helicase activity of Nsp13 in an ion-dependent manner-inhibiting it under low-salt conditions but enhancing it under high-salt conditions. These findings reveal an ion concentration-dependent regulatory mechanism that enables SARS-CoV-2 N to dynamically switch between distinct biochemical states, thereby supporting viral adaptability and providing new insights into antiviral development.

Open Access PDF

Concepts	Keywords
Antiviral	Biochemistry
Host	Biophysics
Proteins	Virology
Viral

Semantics

Type	Source	Name
pathway	KEGG	Viral replication
drug	DRUGBANK	Coenzyme M
drug	DRUGBANK	Carboxyamidotriazole
disease	MESH	COVID 19
disease	MESH	syndrome
disease	MESH	acute respiratory distress syndrome
disease	MESH	respiratory failure
disease	MESH	inflammation
disease	MESH	sepsis
disease	MESH	injury
disease	MESH	heart failure
disease	MESH	viral infections
disease	MESH	infection
disease	MESH	NTD
drug	DRUGBANK	ANX-510
disease	MESH	coronavirus infection
drug	DRUGBANK	Huperzine B
pathway	KEGG	Homologous recombination
pathway	REACTOME	Metabolism
pathway	REACTOME	Autophagy
drug	DRUGBANK	ATP
drug	DRUGBANK	Tretamine
drug	DRUGBANK	Isoxaflutole
disease	MESH	genomic instability
pathway	REACTOME	Translation
pathway	KEGG	Motor proteins
disease	MESH	dissociation
drug	DRUGBANK	Tromethamine
drug	DRUGBANK	Hyaluronic acid
disease	MESH	included
drug	DRUGBANK	Ademetionine
drug	DRUGBANK	L-Phenylalanine
disease	MESH	mul
drug	DRUGBANK	Esomeprazole
disease	MESH	tar
disease	MESH	Plan
drug	DRUGBANK	(S)-Des-Me-Ampa
disease	MESH	Pneumonia
drug	DRUGBANK	Vorinostat
disease	MESH	Dis
disease	MESH	Park
disease	MESH	death
drug	DRUGBANK	L-Aspartic Acid
drug	DRUGBANK	Guanosine
pathway	REACTOME	Cellular Senescence
pathway	REACTOME	Selective autophagy
drug	DRUGBANK	Guanine
drug	DRUGBANK	Naproxen
disease	MESH	tic
drug	DRUGBANK	Sodium Chloride
drug	DRUGBANK	Ammonia
drug	DRUGBANK	Dextrose unspecified form
disease	MESH	Severe Acute Respiratory Syndrome
disease	MESH	strains
drug	DRUGBANK	Ampicillin
disease	MESH	shock
drug	DRUGBANK	Kanamycin
drug	DRUGBANK	Isopropyl beta-D-thiogalactopyranoside
drug	DRUGBANK	Water
drug	DRUGBANK	Edetic Acid
drug	DRUGBANK	Sodium lauryl sulfate
disease	MESH	SDS
drug	DRUGBANK	Glycerin
drug	DRUGBANK	Flunarizine
drug	DRUGBANK	Dextran
drug	DRUGBANK	Biotin
disease	MESH	Image
disease	MESH	rad
disease	MESH	IBM
drug	DRUGBANK	Fluorescein
disease	MESH	kdn+Pn
disease	MESH	SFM