Biochemical characterization of SARS-CoV-2 nucleocapsid protein

Zeng, Weihong; Liu, Guangfeng; Ma, Huan; Zhao, Dan; Yu, Yang; Liu, Muziying; Mohammed, Ahmed; Zhao, Chi; Yang, Yun; Xie, Jiajia; Ding, Changming; Ma, Xiaoling; Weng, Jianping; Gao, Yong; He, Hongliang; Jin, Tengchuan

doi:10.1016/j.bbrc.2020.04.136

Cited by 431 publications

(491 citation statements)

References 31 publications

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“…expressed during infection 155,156 . N binds viral RNA through both its Nand C-terminal domains, connected by a disordered SR-rich linkage region 157,158 . Of note, given its high abundance within the viral particle, N is the first viral protein released in the host, prior to viral RNA translation.…”

Section: Nsp14 Associates With Rna Decapping and Deadenylation Host Fmentioning

confidence: 99%

Global BioID-based SARS-CoV-2 proteins proximal interactome unveils novel ties between viral polypeptides and host factors involved in multiple COVID19-associated mechanisms

Laurent

Sofianatos

Komarova

et al. 2020

Preprint

128

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The worldwide SARS-CoV-2 outbreak poses a serious challenge to human societies and economies. SARS-CoV-2 proteins orchestrate complex pathogenic mechanisms that underlie COVID-19 disease. Thus, understanding how viral polypeptides rewire host protein networks enables better-founded therapeutic research. In complement to existing proteomic studies, in this study we define the first proximal interaction network of SARS-CoV-2 proteins, at the whole proteome level in human cells. Applying a proximity-dependent biotinylation (BioID)-based approach greatly expanded the current knowledge by detecting interactions within poorly soluble compartments, transient, and/or of weak affinity in living cells. Our BioID study was complemented by a stringent filtering and uncovered 2,128 unique cellular targets (1,717 not previously associated with SARS-CoV-1 or 2 proteins) connected to the N- and C-ter BioID-tagged 28 SARS-CoV-2 proteins by a total of 5,415 (5,236 new) proximal interactions. In order to facilitate data exploitation, an innovative interactive 3D web interface was developed to allow customized analysis and exploration of the landscape of interactions (accessible at http://www.sars-cov-2-interactome.org/). Interestingly, 342 membrane proteins including interferon and interleukin pathways factors, were associated with specific viral proteins. We uncovered ORF7a and ORF7b protein proximal partners that could be related to anosmia and ageusia symptoms. Moreover, comparing proximal interactomes in basal and infection-mimicking conditions (poly(I:C) treatment) allowed us to detect novel links with major antiviral response pathway components, such as ORF9b with MAVS and ISG20; N with PKR and TARB2; NSP2 with RIG-I and STAT1; NSP16 with PARP9-DTX3L. Altogether, our study provides an unprecedented comprehensive resource for understanding how SARS-CoV-2 proteins orchestrate host proteome remodeling and innate immune response evasion, which can inform development of targeted therapeutic strategies.

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Section: Nsp14 Associates With Rna Decapping and Deadenylation Host Fmentioning

confidence: 99%

Global BioID-based SARS-CoV-2 proteins proximal interactome unveils novel ties between viral polypeptides and host factors involved in multiple COVID19-associated mechanisms

Laurent

Sofianatos

Komarova

et al. 2020

Preprint

128

View full text Add to dashboard Cite

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“…This is in agreement with other studies that used slightly different sequences/alignments. [34][35] The N protein sequence of MERS-CoV shares only 42% to 44% similarity with the SARS-CoV-1 and SARS-CoV-2 N protein, respectively.…”

Section: Phosphorylation On Nucleocapsid Proteinmentioning

confidence: 99%

“…6 Early studies, including recent review articles about the N protein, suggested that the N protein is a phosphoprotein and does not bear glycans on its backbone. 24…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Nucleocapsid protein is decorated with multiple N- and O-glycans

Supekar

Shajahan

Gleinich

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19) started at the end of 2019 in Wuhan, China has spread rapidly and became a pandemic. Since there is no therapy available that is proven as fully protective against COVID-19, a vaccine to protect against deadly COVID-19 is urgently needed. Nucleocapsid protein (N protein), is one of the most abundant proteins in coronaviruses and is a potential target for both vaccine development and point of care diagnostics. The variable mass of N protein (45 to 60 kDa), suggests the presence of post-translational modifications (PTMs), and it is critical to clearly define these PTMs to gain the structural understanding necessary for further vaccine research. There have been several reports suggesting that the N protein is phosphorylated but lacks glycosylation. Our comprehensive glycomics and glycoproteomics experiments confirm that the N protein is highly O-glycosylated and also contains significant levels of N-glycosylation. We were able to confirm the presence of O-glycans on seven sites with substantial glycan occupancy, in addition to less abundant O-glycans on four sites. We also detected N-glycans on two out of five potential N-glycosylation sites. Moreover, we were able to confirm one phosphorylation site. Recent studies have indicated that the N protein can serve as an important diagnostic marker for coronavirus disease and a major immunogen by priming protective immune responses. Thus, detailed structural characterization of the N protein may provide useful insights for understanding the roles of glycosylation on viral pathogenesis and also in vaccine design and development.

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“…Importantly, a significant percentage of those infected are asymptomatic, with studies finding that 20% to over 40% of cases show no symptoms [2][3][4] , a condition that helps the silent spread of the disease. SARS-CoV-2 is an enveloped virus with a nucleocapsid made up of single-stranded RNA bound to protein N (Nucleocapsid), surrounded by a lipid membrane that contains structural proteins M (Membrane), E (Envelop) and S (Spike) [5][6][7][8] . The structure of protein S gives the virus its distinctive crown of spikes and is responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor, which allows the virus to enter the host cell 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Highly predictive regression model of active cases of COVID-19 in a population by screening wastewater viral load

Vallejo

Rumbo‐Feal

Conde

et al. 2020

Preprint

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The quantification of the SARS-CoV-2 load in wastewater has emerged as a useful method to monitor COVID-19 outbreaks in the community. This approach was implemented in the metropolitan area of A Coruña (NW Spain), where wastewater from the treatment plant of Bens was analyzed to track the epidemic’s dynamic in a population of 369,098 inhabitants. We developed statistical regression models that allowed us to estimate the number of infected people from the viral load detected in the wastewater with a reliability close to 90%. This is the first wastewater-based epidemiological model that could potentially be adapted to track the evolution of the COVID-19 epidemic anywhere in the world, monitoring both symptomatic and asymptomatic individuals. It can help to understand with a high degree of reliability the true magnitude of the epidemic in a place at any given time and can be used as an effective early warning tool for predicting outbreaks.

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Biochemical characterization of SARS-CoV-2 nucleocapsid protein

Cited by 431 publications

References 31 publications

Global BioID-based SARS-CoV-2 proteins proximal interactome unveils novel ties between viral polypeptides and host factors involved in multiple COVID19-associated mechanisms

Global BioID-based SARS-CoV-2 proteins proximal interactome unveils novel ties between viral polypeptides and host factors involved in multiple COVID19-associated mechanisms

SARS-CoV-2 Nucleocapsid protein is decorated with multiple N- and O-glycans

Highly predictive regression model of active cases of COVID-19 in a population by screening wastewater viral load

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