4.7 Review

Why do SARS-CoV-2 NSPs rush to the ER?

Journal

JOURNAL OF NEUROLOGY
Volume 268, Issue 6, Pages 2013-2022

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00415-020-10197-8

Keywords

COVID-19; Double-membrane vesicle; SARS-CoV-2; Endoplasmic reticulum stress; Golgi apparatus fragmentation

Funding

  1. NIH-NIA [R01-AG054411]

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The NSPs of the virus play a crucial role in establishing the replication and transcription complex by hijacking the endoplasmic reticulum membrane, potentially leading to central nervous system damage and neurodegeneration. Research on these NSPs will not only reveal their specific role in viral infection but also aid in the discovery of novel targeted drugs.
SARS-CoV-2, which led to the 2020 global pandemic, is responsible for the Coronavirus Disease 2019 (COVID-19), a respiratory illness, and presents a tropism for the central nervous system. Like most members of this family, the virus is composed of structural and non-structural proteins (NSPs). The non-structural proteins are critical elements of the replication and transcription complex (RTC), as well as immune system evasion. Through hijacking the endoplasmic reticulum (ER) membrane, NSPs help the virus establish the RTC, inducing ER stress after membrane rearrangement and causing severe neuronal disturbance. In this review, we focus on the role of Nsp3, 4, and 6 in intracellular membrane rearrangement and evaluate the potential disruption of the central nervous system and the neurodegeneration which it could trigger. Studies of these NSPs will not only bring to light their specific role in viral infection but also facilitate the discovery of novel targeted drugs.

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