Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response

Astuti, Indwiani; Ysrafil,

doi:10.1016/j.dsx.2020.04.020

Cited by 941 publications

(992 citation statements)

References 53 publications

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“…There are four major structural proteins present on the virus, the Spike glycoprotein, the Envelope protein, the Membrane protein and the Nucleocapsid. Each of the proteins performs specific functions in receptor binding, viral assembly and genome release [16]. One of the first and largest structural proteins of the Coronavirus is the Spike glycoprotein [17].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations

Rath¹,

Kumar

2020

Preprint

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Statistical and epidemiological data imply temperature sensitivity of the SARS-CoV-2 coronavirus. However, the molecular level understanding of the virus structure at different temperature is still not clear. Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. In this study, we performed an all atom molecular dynamics simulation to study the effect of temperature on the structure of the Spike protein. After 200ns of simulation at different temperatures, we came across some interesting phenomena exhibited by the protein. We found that the solvent exposed domain of Spike protein, namely S1, is more mobile than the transmembrane domain, S2. Structural studies implied the presence of several charged residues on the surface of N-terminal Domain of S1 which are optimally oriented at 10-C. Bioinformatics analyses indicated that it is capable of binding to other human receptors and should not be disregarded. Additionally, we found that receptor binding motif (RBM), present on the receptor binding domain (RBD) of S1, begins to close around temperature of 40 C and attains a completely closed conformation at 50 C. The closed conformation disables its ability to bind to ACE2, due to the burying of its receptor binding residues. Our results clearly show that there are active and inactive states of the protein at different temperatures. This would not only prove beneficial for understanding the fundamental nature of the virus, but would be also useful in the development of vaccines and therapeutics.3 Graphical Abstract Highlights: Statistical and epidemiological evidence show that external climatic conditions influence the SARS-CoV infectivity, but we still lack a molecular level understanding of the same. Here, we study the influence of temperature on the structure of the Spike glycoprotein, the outermost structural protein, of the virus which binds to the human receptor ACE2. Results show that the Spike's S1 domain is very sensitive to external atmospheric conditions compared to the S2 transmembrane domain. The N-terminal domain comprises of several solvent exposed charged residues that are capable of binding to human proteins. The region is specifically stable at temperatures ranging around 10-30 C.  The Receptor Binding Motif adopts a closed conformation at 40 C and completely closes at higher temperatures making it unsuitable of binding to human receptors Abbreviations: RBD -receptor binding domain; NTD -N -Terminal Domain; RBMreceptor binding motif; ACE2-Angiotensin Converting enzyme 2

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Section: Introductionmentioning

confidence: 99%

Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations

Rath¹,

Kumar

2020

Preprint

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“…It has been reported that the Spike (S) protein of SARS-CoV-2 binds with high a nity to human ACE2, and before SARS-CoV-2's entry into the cells [16][17][18], the S protein is subjected to a priming process via serine protease TMPRSS2 in order to permit the attachment of viral particles to ACE2 and thus on cell surface [19,20]. Therefore, SARS-CoV-2 can directly attack cardiac muscle cells through this pathway [21][22][23]. This entry mechanism is con rmed by the fact that TMPRSS2 inhibition or TMPRSS2-KO mice show both decreased, though not abolished, S protein priming, and reduced viral entry, spread, as well as, in ammatory chemokine and cytokine release [19].…”

Section: Discussionmentioning

confidence: 99%

A nomogramic model based on clinical and laboratory parameters at admission for predicting the survival of COVID-19 patients

Wang

Huang

et al. 2020

Preprint

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Background and AimCOVID-19 has become a major global threat. The present study aimed to develop a nomogram model to predict the survival of COVID-19 patients based on their clinical and laboratory data at admission.Methods COVID-19 patients who were admitted at Hankou Hospital and Huoshenshan Hospital in Wuhan, China from January 12, 2020 to March 20, 2020, whose outcome during the hospitalization was known, were retrospectively reviewed. The categorical variables were compared using Pearson’s χ2-test or Fisher’s exact test, and continuous variables were analyzed using Student’s t-test or Mann Whitney U-test, as appropriate. Then, variables with a P-value of ≤0.1 were included in the log-binomial model, and merely these independent risk factors were used to establish the nomogram model. The discrimination of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), and internally verified using the Bootstrap method.Results A total of 262 patients (134 surviving and 128 non-surviving patients) were included in the analysis. Seven variables, which included age (relative risk [RR]: 0.905, 95% confidence interval [CI]: 0.868-0.944; P<0.001), chronic heart disease (CHD, RR: 0.045, 95% CI: 0.0097-0.205; P<0.001, the percentage of lymphocytes (Lym%, RR: 1.125, 95% CI: 1.041-1.216; P=0.0029), platelets (RR: 1.008, 95% CI: 1.003-1.012; P=0.001), C-reaction protein (RR: 0.982, 95% CI: 0.973-0.991; P<0.001), lactate dehydrogenase (LDH, RR: 0.993, 95% CI: 0.990-0.997; P<0.001) and D-dimer (RR: 0.734, 95% CI: 0.617-0.879; P<0.001), were identified as the independent risk factors. The nomogram model based on these factors exhibited a good discrimination, with an AUC of 0.948 (95% CI: 0.923-0.973). ConclusionA nomogram based on age, CHD, Lym%, platelets, C-reaction protein, LDH and D-dimer was established to accurately predict the prognosis of COVID-19 patients. This can be used as an alerting tool for clinicians to take early intervention measures, when necessary.

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“…E protein is a small viral transmembrane protein which helps in the assembly of the virions by forming ion channels inside the host cell [5]. M protein is the most abundant protein present on the viral membrane, important for morphogenesis and viral assembly [2]. N protein is responsible for the packaging of the viral genome and plays an important role in viral assembly [13].…”

Section: Brief Reportmentioning

confidence: 99%

Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype

Gaurav

Pandey

Puvar

et al. 2020

Preprint

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Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. Studies on SARS-CoV-2 are being carried out at an unprecedented rate to tackle this threat. Genomics studies, in particular, are indispensable to elucidate the dynamic nature of the RNA genome of SARS-CoV-2. RNA viruses are marked by their unique ability to undergo high rates of mutation in their genome, much more frequently than their hosts, which diversifies their strengths qualifying them to elude host immune response and amplify drug resistance. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. In addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36nucleotide deletion in ORF8 of SARS-CoV-2. Our results corroborate with the earlier reported 29-nucleotide deletion in SARS, which was frequent during the early stage of human-to-human transmission. The results will be useful to understand the biology of SARS-CoV-2 and itsattenuation for vaccine development.

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response

Cited by 941 publications

References 53 publications

Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations

Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations

A nomogramic model based on clinical and laboratory parameters at admission for predicting the survival of COVID-19 patients

Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype

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