scholarly journals Integrative multi-omics landscape of non-structural protein 3 of severe acute respiratory syndrome coronaviruses

2021 ◽  
Author(s):  
Ruona Shi ◽  
Zhenhuan Feng ◽  
Xiaofei Zhang

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently a global pandemic. Extensive investigations have been performed to study the clinical and cellular effects of SARS-CoV-2 infection. Mass spectrometry-based proteomics studies have revealed the cellular changes due to the infection and identified a plethora of interactors for all SARS-CoV-2 components, except for the longest non-structural protein 3 (NSP3). Here, we expressed the full-length NSP3 proteins of SARS-CoV and SARS-CoV-2 to investigate their unique and shared functions using multi-omics methods. We conducted interactome, phosphoproteome, ubiquitylome, transcriptome, and proteome analyses of NSP3-expressing cells. We found that NSP3 plays essential roles in cellular functions such as RNA metabolism and immune response such as NF-kB signal transduction. Interestingly, we showed that SARS-CoV-2 NSP3 has both endoplasmic reticulum and mitochondrial localizations. In addition, SARS-CoV-2 NSP3 is more closely related to mitochondrial ribosomal proteins, whereas SARS-CoV NSP3 is related to the cytosolic ribosomal proteins. In summary, our multi-omics studies of NSP3 enhance our understanding of the functions of NSP3 and offer valuable insights for the development of anti-SARS strategies.

BIOspektrum ◽  
2021 ◽  
Vol 27 (4) ◽  
pp. 368-371
Author(s):  
Konstantin Sparrer ◽  
Frank Kirchhoff

AbstractThe Coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate its own replication and avoid immune control, SARS-CoV-2 manipulates its target cells. Our results revealed that the SARS-CoV-2 non-structural protein 1 (Nsp1) plays a key role in viral immune evasion. It blocks the mRNA tunnel of the cellular ribosome, resulting in a shutdown of translation and strong attenuation of the host’s antiviral immune response.


2021 ◽  
Vol 7 (10) ◽  
pp. eabf1004
Author(s):  
Boris Krichel ◽  
Ganesh Bylapudi ◽  
Christina Schmidt ◽  
Clement Blanchet ◽  
Robin Schubert ◽  
...  

Coronaviruses infect many different species including humans. The last two decades have seen three zoonotic coronaviruses, with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) causing a pandemic in 2020. Coronaviral non-structural proteins (nsps) form the replication-transcription complex (RTC). Nsp7 and nsp8 interact with and regulate the RNA-dependent RNA-polymerase and other enzymes in the RTC. However, the structural plasticity of nsp7+8 complexes has been under debate. Here, we present the framework of nsp7+8 complex stoichiometry and topology based on native mass spectrometry and complementary biophysical techniques of nsp7+8 complexes from seven coronaviruses in the genera Alpha- and Betacoronavirus including SARS-CoV-2. Their complexes cluster into three groups, which systematically form either heterotrimers or heterotetramers or both, exhibiting distinct topologies. Moreover, even at high protein concentrations, SARS-CoV-2 nsp7+8 consists primarily of heterotetramers. From these results, the different assembly paths can be pinpointed to specific residues and an assembly model proposed.


2020 ◽  
Vol 21 (19) ◽  
pp. 7375 ◽  
Author(s):  
Annika Rogstam ◽  
Maria Nyblom ◽  
Signe Christensen ◽  
Celeste Sele ◽  
Vladimir O. Talibov ◽  
...  

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), causing Coronavirus Disease 19 (COVID-19), emerged at the end of 2019 and quickly spread to cause a global pandemic with severe socio-economic consequences. The early sequencing of its RNA genome revealed its high similarity to SARS, likely to have originated from bats. The SARS-CoV-2 non-structural protein 10 (nsp10) displays high sequence similarity with its SARS homologue, which binds to and stimulates the 3′-to-5′ exoribonuclease and the 2′-O-methlytransferase activities of nsps 14 and 16, respectively. Here, we report the biophysical characterization and 1.6 Å resolution structure of the unbound form of nsp10 from SARS-CoV-2 and compare it to the structures of its SARS homologue and the complex-bound form with nsp16 from SARS-CoV-2. The crystal structure and solution behaviour of nsp10 will not only form the basis for understanding the role of SARS-CoV-2 nsp10 as a central player of the viral RNA capping apparatus, but will also serve as a basis for the development of inhibitors of nsp10, interfering with crucial functions of the replication–transcription complex and virus replication.


2020 ◽  
Vol 21 (21) ◽  
pp. 8141
Author(s):  
Federico Biscetti ◽  
Maria Margherita Rando ◽  
Elisabetta Nardella ◽  
Andrea Leonardo Cecchini ◽  
Piergiorgio Bruno ◽  
...  

The 2019 novel coronavirus [2019-nCoV], which started to spread from December 2019 onwards, caused a global pandemic. Besides being responsible for the severe acute respiratory syndrome 2 [SARS-CoV-2], the virus can affect other organs causing various symptoms. A close relationship between SARS-CoV-2 and the cardiovascular system has been shown, demonstrating an epidemiological linkage between SARS-CoV-2 and cardiac injury. There are emerging data regarding possible direct myocardial damage by 2019-nCoV. In this review, the most important available evidences will be discussed to clarify the precise mechanisms of cardiovascular injury in SARS-CoV-2 patients, even if further researches are needed.


2020 ◽  
Vol 48 (2) ◽  
pp. 613-620
Author(s):  
Clara Ortegón Salas ◽  
Katharina Schneider ◽  
Christopher Horst Lillig ◽  
Manuela Gellert

Processing of and responding to various signals is an essential cellular function that influences survival, homeostasis, development, and cell death. Extra- or intracellular signals are perceived via specific receptors and transduced in a particular signalling pathway that results in a precise response. Reversible post-translational redox modifications of cysteinyl and methionyl residues have been characterised in countless signal transduction pathways. Due to the low reactivity of most sulfur-containing amino acid side chains with hydrogen peroxide, for instance, and also to ensure specificity, redox signalling requires catalysis, just like phosphorylation signalling requires kinases and phosphatases. While reducing enzymes of both cysteinyl- and methionyl-derivates have been characterised in great detail before, the discovery and characterisation of MICAL proteins evinced the first examples of specific oxidases in signal transduction. This article provides an overview of the functions of MICAL proteins in the redox regulation of cellular functions.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 748-752
Author(s):  
Swapnali Khabade ◽  
Bharat Rathi ◽  
Renu Rathi

A novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes severe acute respiratory syndrome and spread globally from Wuhan, China. In March 2020 the World Health Organization declared the SARS-Cov-2 virus as a COVID- 19, a global pandemic. This pandemic happened to be followed by some restrictions, and specially lockdown playing the leading role for the people to get disassociated with their personal and social schedules. And now the food is the most necessary thing to take care of. It seems the new challenge for the individual is self-isolation to maintain themselves on the health basis and fight against the pandemic situation by boosting their immunity. Food organised by proper diet may maintain the physical and mental health of the individual. Ayurveda aims to promote and preserve the health, strength and the longevity of the healthy person and to cure the disease by properly channelling with and without Ahara. In Ayurveda, diet (Ahara) is considered as one of the critical pillars of life, and Langhana plays an important role too. This article will review the relevance of dietetic approach described in Ayurveda with and without food (Asthavidhi visheshaytana & Lanhgan) during COVID-19 like a pandemic.


2020 ◽  
Author(s):  
Paul Fontelo ◽  
Mrigendra Bastola ◽  
Craig Locatis ◽  
Fang Liu

UNSTRUCTURED The global pandemic of COVID-19 has generated an unprecedented number of research papers from clinicians and scientists worldwide. We searched PubMed for articles on coronaviruses from 1970 to June 2020. Surges of publications occurred in 2003 from SARS and, again in 2012 from MERS. Although the name COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was only announced by WHO in February 2020, the number of publications has already exceeded 16000 by June this year. China and the US lead in publications, but a significant number also come from countries hardest hit by the illness. International collaborative publishing is significant. Since these publications are generally free to access worldwide, it provides a rich evidence base for clinicians and scientists combatting the COVID-19 pandemic.


2021 ◽  
Vol 9 (6) ◽  
pp. 1259
Author(s):  
Carla Prezioso ◽  
Ugo Moens ◽  
Giuseppe Oliveto ◽  
Gabriele Brazzini ◽  
Francesca Piacentini ◽  
...  

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a global pandemic. Our goal was to determine whether co-infections with respiratory polyomaviruses, such as Karolinska Institutet polyomavirus (KIPyV) and Washington University polyomavirus (WUPyV) occur in SARS-CoV-2 infected patients. Oropharyngeal swabs from 150 individuals, 112 symptomatic COVID-19 patients and 38 healthcare workers not infected by SARS-CoV-2, were collected from March 2020 through May 2020 and tested for KIPyV and WUPyV DNA presence. Of the 112 SARS-CoV-2 positive patients, 27 (24.1%) were co-infected with KIPyV, 5 (4.5%) were positive for WUPyV, and 3 (2.7%) were infected simultaneously by KIPyV and WUPyV. Neither KIPyV nor WUPyV DNA was detected in samples of healthcare workers. Significant correlations were found in patients co-infected with SARS-CoV-2 and KIPyV (p < 0.05) and between SARS-CoV-2 cycle threshold values and KIPyV, WUPyV and KIPyV and WUPyV concurrently detected (p < 0.05). These results suggest that KIPyV and WUPyV may behave as opportunistic respiratory pathogens. Additional investigations are needed to understand the epidemiology and the prevalence of respiratory polyomavirus in COVID-19 patients and whether KIPyV and WUPyV could potentially drive viral interference or influence disease outcomes by upregulating SARS-CoV-2 replicative potential.


2021 ◽  
Vol 8 ◽  
pp. 204993612110320
Author(s):  
Robert Rosolanka ◽  
Andres F. Henao-Martinez ◽  
Larissa Pisney ◽  
Carlos Franco-Paredes ◽  
Martin Krsak

Deeper understanding of the spread, morbidity, fatality, and development of immune response associated with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is necessary in order to establish an appropriate epidemiological and clinical response. Exposure control represents a key part of the combat against COVID-19, as the effectiveness of current therapeutic options remains partial. Since the preventive measures have not been sufficiently able to slow down this pandemic, in this article we explore some of the pertinent knowledge gaps, while overall looking to effective vaccination strategies as a way out. Early on, such strategies may need to rely on counting the convalescents as protected in order to speed up the immunization of the whole population.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexandre Maciel-Guerra ◽  
Necati Esener ◽  
Katharina Giebel ◽  
Daniel Lea ◽  
Martin J. Green ◽  
...  

AbstractStreptococcus uberis is one of the leading pathogens causing mastitis worldwide. Identification of S. uberis strains that fail to respond to treatment with antibiotics is essential for better decision making and treatment selection. We demonstrate that the combination of supervised machine learning and matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) mass spectrometry can discriminate strains of S. uberis causing clinical mastitis that are likely to be responsive or unresponsive to treatment. Diagnostics prediction systems trained on 90 individuals from 26 different farms achieved up to 86.2% and 71.5% in terms of accuracy and Cohen’s kappa. The performance was further increased by adding metadata (parity, somatic cell count of previous lactation and count of positive mastitis cases) to encoded MALDI-TOF spectra, which increased accuracy and Cohen’s kappa to 92.2% and 84.1% respectively. A computational framework integrating protein–protein networks and structural protein information to the machine learning results unveiled the molecular determinants underlying the responsive and unresponsive phenotypes.


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