Open AccessSARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA
Author(s) -
Amanda Jack,
Luke S. Ferro,
Michael J. Trnka,
Eddie Wehri,
Amrut Nadgir,
Xammy Nguyenla,
Douglas Fox,
Katelyn Costa,
Sarah A. Stanley,
Julia Schaletzky,
Ahmet Yıldız
Publication year - 2021
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3001425
Subject(s) - rna , biology , genome , coronavirus , virology , rna binding protein , dna , gene , microbiology and biotechnology , genetics , covid-19 , disease , infectious disease (medical specialty) , medicine , pathology
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a pandemic that seriously threatens global health. SARS-CoV-2 propagates by packaging its RNA genome into membrane enclosures in host cells. The packaging of the viral genome into the nascent virion is mediated by the nucleocapsid (N) protein, but the underlying mechanism remains unclear. Here, we show that the N protein forms biomolecular condensates with viral genomic RNA both in vitro and in mammalian cells. While the N protein forms spherical assemblies with homopolymeric RNA substrates that do not form base pairing interactions, it forms asymmetric condensates with viral RNA strands. Cross-linking mass spectrometry (CLMS) identified a region that drives interactions between N proteins in condensates, and deletion of this region disrupts phase separation. We also identified small molecules that alter the size and shape of N protein condensates and inhibit the proliferation of SARS-CoV-2 in infected cells. These results suggest that the N protein may utilize biomolecular condensation to package the SARS-CoV-2 RNA genome into a viral particle.