Specific Viral RNA Drives the SARS CoV-2 Nucleocapsid to Phase Separate

Overview

Journal bioRxiv

Date 2020 Jun 27

PMID 32587965

Authors

Christiane Iserman

Christine Roden

Mark Boerneke

Rachel Sealfon

Grace McLaughlin

Irwin Jungreis

Chris Park

Avinash Boppana

Ethan Fritch

Yixuan J Hou

Chandra Theesfeld

Olga G Troyanskaya

Ralph S Baric

Timothy P Sheahan

Kevin Weeks

Amy S Gladfelter

Affiliations

Soon will be listed here.

Abstract

A mechanistic understanding of the SARS-CoV-2 viral replication cycle is essential to develop new therapies for the COVID-19 global health crisis. In this study, we show that the SARS-CoV-2 nucleocapsid protein (N-protein) undergoes liquid-liquid phase separation (LLPS) with the viral genome, and propose a model of viral packaging through LLPS. N-protein condenses with specific RNA sequences in the first 1000 nts (5'-End) under physiological conditions and is enhanced at human upper airway temperatures. N-protein condensates exclude non-packaged RNA sequences. We comprehensively map sites bound by N-protein in the 5'-End and find preferences for single-stranded RNA flanked by stable structured elements. Liquid-like N-protein condensates form in mammalian cells in a concentration-dependent manner and can be altered by small molecules. Condensation of N-protein is sequence and structure specific, sensitive to human body temperature, and manipulatable with small molecules thus presenting screenable processes for identifying antiviral compounds effective against SARS-CoV-2.

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