Liquid-liquid phase separation of nucleocapsid proteins during SARS-CoV-2 and HIV-1 replication

The leap of retroviruses and coronaviruses from animal hosts to humans has led to two ongoing pandemics and tens of millions of deaths worldwide. Retrovirus and coronavirus nucleocapsid proteins have been stud-ied extensively as potential drug targets due to their central roles in virus replication, among which is their capacity to bind their respective genomic RNAs for packaging into nascent virions. This review focuses on fundamental studies of these nucleocapsid proteins and how their intrinsic abilities to condense through liquid-liquid phase separation (LLPS) contribute to viral replication. Therapeutic targeting of these conden-sates and methodological advances are also described to address future questions on how phase separation contributes to viral replication.

Automated summary

The leap of retroviruses and coronaviruses from animal hosts to humans has caused two ongoing pandemics and resulted in tens of millions of deaths worldwide. Extensive studies have been conducted on retrovirus and coronavirus nucleocapsid proteins as potential drug targets due to their crucial roles in virus replication, particularly their ability to bind their respective genomic RNAs for packaging into nascent virions. This review primarily focuses on the fundamental studies of these nucleocapsid proteins and how their condensation through liquid-liquid phase separation (LLPS) contributes to viral replication. Therapeutic targeting of these condensates and advances in methodologies are also discussed to address future inquiries concerning the role of phase separation in viral replication.