Why do SARS-CoV-2 NSPs rush to the ER?
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REVIEW
Why do SARS‑CoV‑2 NSPs rush to the ER? Maryline Santerre1 · Sterling P. Arjona1 · Charles NS Allen1 · Natalia Shcherbik2 · Bassel E. Sawaya1,3 Received: 26 June 2020 / Revised: 15 August 2020 / Accepted: 27 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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. Keywords COVID-19 · Double-membrane vesicle · SARS-CoV-2 · Endoplasmic reticulum stress · Golgi apparatus fragmentation Abbreviations COVID-19 Coronavirus disease 2019 DMV Double-membrane vesicle MSA Multiple sequence alignment SARS Severe acute respiratory syndrome SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2
* Maryline Santerre [email protected] * Bassel E. Sawaya [email protected] 1
Molecular Studies of Neurodegenerative Diseases Lab, Lewis Katz School of Medicine, Fels Institute for Cancer Research, Temple University, 3307 North Broad Street, Philadelphia, PA 19140, USA
2
Department for Cell Biology and Neuroscience, School of Osteopathic Medicine, Rowan University, 2 Medical Center Drive, Stratford, NJ 08084, USA
3
Department of Neurology, Lewis Katz School of Medicine - Temple University Philadelphia, Philadelphia, PA 19140, USA
Background Since the discovery of the first coronaviruses (CoV) by Tyrrell and Bynoe in 1965 [1], more strains have emerged. Only two circulating human coronaviruses (HCoVs), HCoV-229E [2] and HCoV-OC43 [3], were described as the frequent cause of the common cold until 2002–2003 when the severe acute respiratory syndrome (SARS)-CoV spread into the human population in China [4, 5]. Then, two new coronaviruses, CoV NL63 in 2004 (alphacoronavirus) [6] and HKU1 in 2005 (betacoronavirus) [7], were discovered. Another coronavirus, the MERS-CoV, emerged in the Middle East and engenders lower respiratory tract infections with high mortality [8]. HCoVs were considered relatively harmless until the SARS outbreak in 2003, where they appeared clinically for the first time as a severe respiratory illness with high mortality and morbidity. Coronaviruses have been identified to infect a wide variety of anima
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