Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (501)

ProteinN (123)

NSP5 (55)

ComplexRdRp (39)

ProteinE (33)


SARS-CoV-2 Proteins
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    The second wave of COVID-19 MESHD incidence and deaths MESHD in Germany - driven by values, social status and migration background? A county-scale explainable machine learning approach

    Authors: Gabriele Doblhammer; Constantin Reinke; Daniel Kreft

    doi:10.1101/2021.04.14.21255474 Date: 2021-04-14 Source: medRxiv

    There is a general consensus that SARS-CoV-2 infections MESHD and COVID-19 MESHD deaths MESHD have hit lower social groups the hardest, however, for Germany individual level information on socioeco-nomic characteristics of infections and deaths does not exist. The aim of this study was to identify the key features explaining SARS-CoV-2 infections MESHD and COVID-19 MESHD deaths during the upswing of the second wave in Germany. We considered information on COVID-19 MESHD diagnoses and deaths from 1. October to 15. De-cember 2021 on the county-level, differentiating five two-week time periods. We used 155 indicators to characterize counties in nine geographic, social, demographic, and health do-mains. For each period, we calculated directly age-standardized COVID-19 MESHD incidence and death MESHD rates on the county level. We trained gradient boosting models to predict the inci-dence and death rates with the 155 characteristics of the counties for each period. To ex-plore the importance and the direction of the correlation of the regional indicators we used the SHAP HGNC procedure. We categorized the top 20 associations identified by the Shapley values into twelve categories depicting the correlation between the feature and the outcome. We found that counties with low SES were important drivers in the second wave, as were those with high international migration and a high proportion of foreigners and a large nurs-ing home population. During the period of intense exponential increase in infections, the proportion of the population that voted for the Alternative for Germany (AfD) party in the last federal election was among the top characteristics correlated with high incidence and death MESHD rates. We concluded that risky working conditions with reduced opportunities for social distancing and a high chronic disease burden put populations in low-SES counties at higher risk of SARS-CoV-2 infections MESHD and COVID-19 MESHD deaths. In addition, noncompliance with Corona measures and spill-over effects from neighbouring counties increased the spread of the virus. To fur-ther substantiate this finding, we urgently need more data at the individual level.

    Case fatality rates for COVID-19 MESHD are higher than case fatality rates for motor vehicle accidents for individuals over 40 years of age

    Authors: Arjun Puranik; Michiel J.M. Niesen; Emily Lindemer; Patrick Lenehan; Tudor Cristea-Platon; Colin Pawlowski; Venky Soundararajan

    doi:10.1101/2021.04.09.21255193 Date: 2021-04-13 Source: medRxiv

    The death toll of the COVID-19 pandemic MESHD has been unprecedented, due to both the high number of SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD and the seriousness of the disease resulting from these infections. Here, we present mortality rates and case fatality rates for COVID-19 MESHD over the past year compared with other historic leading causes of death MESHD in the United States. Among the risk categories considered, COVID-19 MESHD is the third leading cause of death MESHD for individuals 40 years old and over, with an overall annual mortality rate of 325 deaths MESHD per 100K individuals, behind only cancer MESHD (385 deaths per 100K individuals) and heart disease MESHD (412 deaths per 100K individuals). In addition, for individuals 40 years old and over, the case fatality rate for COVID-19 MESHD is greater than the case fatality rate for motor vehicle accidents. In particular, for the age group 40-49, the relative case fatality rate of COVID-19 MESHD is 1.5 fold (95% CI: [1.3, 1.7]) that of a motor vehicle accident, demonstrating that SARS-CoV-2 infection MESHD may be significantly more dangerous than a car crash for this age group. For older adults, COVID-19 MESHD is even more dangerous, and the relative case fatality rate of COVID-19 MESHD is 29.4 fold (95% CI: [23.2, 35.7]) that of a motor vehicle accident for individuals over 80 years old. On the other hand, motor vehicle accidents have a 4.5 fold (95% CI: [3.9, 5.1]) greater relative case fatality rate compared to COVID-19 MESHD for the age group of 20-29 years. These results highlight the severity of the COVID-19 pandemic MESHD especially for adults above 40 years of age and underscore the need for large-scale preventative measures to mitigate risks for these populations. Given that FDA-authorized COVID-19 MESHD vaccines have now been validated by multiple studies for their outstanding real-world effectiveness and safety, vaccination of all individuals who are over 40 years of age is one of the most pressing public health priorities of our time.

    Epitope classification and RBD binding properties of neutralizing antibodies against SARS-CoV-2 variants of concern

    Authors: Ashlesha Deshpande; Bethany D. Harris; Luis Martinez-Sobrido; James J. Kobie; Mark R Walter

    doi:10.1101/2021.04.13.439681 Date: 2021-04-13 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus-2 MESHD (SAR-CoV-2) causes coronavirus disease 2019 MESHD ( COVID19 MESHD) that is responsible for short and long-term disease, as well as death, in susceptible hosts. The receptor binding domain (RBD) of the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN ( S) protein PROTEIN binds to cell surface angiotensin converting enzyme type-II ( ACE2 HGNC) to initiate viral attachment and ultimately viral pathogenesis. The SARS-CoV-2 S RBD MESHD is a major target of neutralizing antibodies (NAbs) that block RBD - ACE2 HGNC interactions. In this report, NAb-RBD binding epitopes in the protein databank were classified as C1, C1D, C2, C3, or C4 HGNC, using a RBD binding profile (BP), based on NAb-specific RBD buried surface area and used to predict the binding epitopes of a series of uncharacterized NAbs. Naturally occurring SARS-CoV-2 RBD sequence variation was also quantified to predict NAb binding sensitivities to the RBD-variants. NAb and ACE2 HGNC binding studies confirmed the NAb classifications and determined whether the RBD variants enhanced ACE2 HGNC binding to promote viral infectivity, and/or disrupted NAb binding to evade the host immune response. Of 9 single RBD mutants evaluated, K417T, E484K, and N501Y disrupted binding of 65% of the NAbs evaluated, consistent with the assignment of the SARS-CoV-2 P.1 Japan/Brazil strain as a variant of concern (VoC). RBD variants E484K and N501Y exhibited ACE2 HGNC binding equivalent to a Wuhan-1 reference SARS-CoV-2 RBD. While slightly less disruptive to NAb binding, L452R enhanced ACE2 HGNC binding affinity. Thus, the L452R mutant, associated with the SARS-CoV-2 California VoC MESHD (B.1.427/B.1.429-California), has evolved to enhance ACE2 HGNC binding, while simultaneously disrupting C1 and C2 NAb classes. The analysis also identified a non-overlapping antibody pair (1213H7 and 1215D1) that bound to all SARS-CoV-2 RBD variants evaluated, representing an excellent therapeutic option for treatment of SARS-CoV-2 WT MESHD and VoC strains.

    Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

    Authors: Kai Wu; Angela Choi; Matthew Koch; Sayda Elbashir; LingZhi Ma; Diana Lee; Angela Woods; Carole Henry; Charis Palandjian; Anna Hill; Julian Quinones; Naveen Nunna; Adrian B McDermott; Samantha Falcone; Elisabeth Narayanan; Tonya Colpitts; Hamilton Bennett; Kizzmekia Corbett; Robert Seder; Barney S Graham; Guillaume BE Stewart-Jones; Andrea Carfi; Darin K Edwards

    doi:10.1101/2021.04.13.439482 Date: 2021-04-13 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the causative agent of a global pandemic that has led to more than 2.8 million deaths worldwide. Safe and effective vaccines are now available, including Moderna's COVID-19 MESHD vaccine (mRNA-1273) that showed 94% efficacy in prevention of symptomatic COVID-19 MESHD disease in a phase 3 clinical study. mRNA-1273 encodes for a prefusion stabilized full length spike (S) protein PROTEIN of the Wuhan-Hu-1 isolate. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several emerging variants have shown decreased susceptibility to neutralization by vaccine induced immunity, most notably the B.1.351 variant, although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of two updated COVID-19 MESHD mRNA vaccines designed to target emerging SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the S protein PROTEIN found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with 2-doses of mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization in mice. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are currently being evaluated in additional pre-clinical challenge models and in phase 1/2 clinical studies.

    A multiplexed high-throughput neutralization assay reveals a lack of activity against multiple variants after SARS-CoV-2 infection MESHD

    Authors: Craig Fenwick; Priscilla Turelli; Celine Pellaton; Alex Farina; Jeremy Campos; Charlene Raclot; Florence Pojer; Valeria Cagno; Giuseppe Pantaleo; Didier Trono

    doi:10.1101/2021.04.08.21255150 Date: 2021-04-13 Source: medRxiv

    The detection of SARS-CoV-2-specific antibodies in the serum of an individual indicates prior infection or vaccination. However, it provides limited insight into the protective nature of this immune response. Neutralizing antibodies recognizing the viral Spike are far more revealing, yet their measurement traditionally requires virus- and cell-based systems that are costly, time-consuming, poorly flexible and potentially biohazardous. Here we present a cell-free quantitative neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD protein binding to the angiotensin converting enzyme 2 HGNC ( ACE2 HGNC) viral receptor. This high-throughput method matches the performance of the gold standard live virus infectious assay, as verified with a panel of 206 seropositive donors with varying degrees of infection severity and virus-specific IgG titers, achieving 96.7% sensitivity and 100% specificity. Furthermore, it allows for the parallel assessment of neutralizing activities against multiple SARS-CoV-2 Spike PROTEIN variants of concern (VOC), which is otherwise unpredictable even in individuals displaying robust neutralizing antibody responses. Profiling serum samples from 59 hospitalized COVID-19 MESHD patients, we found that although most had high activity against the 2019-nCoV Spike and to a lesser extent the B.1.1.7 variant, only 58% could efficiently neutralize a Spike derivative containing mutations present in the B.1.351 variant. In conclusion, we have developed an assay that has proven its clinical relevance in the large-scale evaluation of effective neutralizing antibody responses to VOC after natural infection and that can be applied to the characterization of vaccine-induced antibody responses and of the potency of human monoclonal antibodies.

    Impairment of SARS-CoV-2 spike PROTEIN glycoprotein maturation and fusion activity by the broad-spectrum anti-infective drug nitazoxanide

    Authors: Anna Riccio; Silvia Santopolo; Antonio Rossi; Sara Piacentini; Jean-Francois Rossignol; Maria Gabriella Santoro

    doi:10.1101/2021.04.12.439201 Date: 2021-04-12 Source: bioRxiv

    The emergence of the highly-pathogenic severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2), the causative agent of COVID-19 MESHD (coronavirus disease-2019), has caused an unprecedented global health crisis, as well as societal and economic disruption. The SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (S), a surface-anchored trimeric class-I fusion glycoprotein essential for entry into host cells, represents a key target for developing vaccines and therapeutics capable of blocking virus invasion. The emergence of several SARS-CoV-2 spike PROTEIN variants that facilitate virus spread and may affect the efficacy of recently developed vaccines, creates great concern and highlights the importance of identifying antiviral drugs to reduce SARS-CoV-2-related morbidity and mortality. Nitazoxanide, a thiazolide originally developed as an antiprotozoal agent with recognized broad-spectrum antiviral activity in-vitro and in clinical studies, was recently shown to be effective against several coronaviruses, including SARS-CoV-2. Using biochemical and pseudovirus entry assays, we now demonstrate that nitazoxanide interferes with the SARS-CoV-2 spike PROTEIN biogenesis, hampering its maturation at an endoglycosidase H-sensitive stage, and hindering its fusion activity in human cells. Besides membrane fusion during virus entry, SARS-CoV-2 S-proteins MESHD S-proteins PROTEIN in infected cells can also trigger receptor-dependent formation of syncytia, observed in-vitro and in COVID-19 MESHD patients tissues, facilitating viral dissemination between cells and possibly promoting immune evasion. Utilizing two different quantitative cell-cell fusion assays, we show that nitazoxanide is effective in inhibiting syncytia formation mediated by different SARS-CoV-2 spike PROTEIN variants in human lung, liver and intestinal cells. The results suggest that nitazoxanide may represent a useful tool in the fight against COVID-19 MESHD infections, inhibiting SARS-CoV-2 replication and preventing spike-mediated syncytia formation.

    ADAM17 inhibition prevents neutrophilia MESHD and lung injury MESHD in a mouse model of Covid-19 MESHD

    Authors: Nathaniel L. Lartey; Salvador Valle-Reyes; Hilda Vargas-Robles; Karina E. Jiménez-Camacho; Idaira M. Guerrero-Fonseca; Ramón Castellanos-Martínez; Armando Montoya-García; Julio García-Cordero; Leticia Cedillo-Barrón; Porfirio Nava; Jessica G. Filisola-Villaseňor; Daniela Roa-Velázquez; Dan I. Zavala-Vargas; Edgar Morales-Ríos; Citlaltepetl Salinas-Lara; Eduardo Vadillo; Michael Schnoor

    doi:10.1101/2021.04.10.439288 Date: 2021-04-11 Source: bioRxiv

    Severe coronavirus disease MESHD coronavirus disease 2019 MESHD ( Covid-19 MESHD) is characterized by lung injury MESHD, cytokine storm and increased neutrophil-to-lymphocyte ratio (NLR). Current therapies focus on reducing viral replication and inflammatory responses, but no specific treatment exists to prevent the development of severe Covid-19 MESHD in infected individuals. Angiotensin-converting enzyme-2 ACE-2) is the receptor for SARS-CoV-2, the virus causing Covid-19 MESHD, but it is also critical for maintaining the correct functionality of lung epithelium and endothelium. Coronaviruses induce activation of a disintegrin and metalloprotease 17 (ADAM17) and shedding of ACE-2 from the cell surface resulting in exacerbated inflammatory responses. Thus, we hypothesized that ADAM17 inhibition ameliorates Covid-19 MESHD-related lung inflammation MESHD. We employed a pre-clinical mouse model using intra-tracheal instillation of a combination of polyinosinic:polycytidylic acid (poly-I:C) and the receptor-binding domain of the SARS-CoV-2 spike PROTEIN protein (RBD-S) to mimic lung damage MESHD associated with Covid-19 MESHD. Histological analysis of inflamed mice confirmed the expected signs of lung injury MESHD including edema MESHD, fibrosis MESHD, vascular congestion and leukocyte infiltration. Moreover, inflamed mice also showed an increased NLR as observed in critically ill Covid-19 MESHD patients. Administration of the ADAM17 inhibitors apratastat and TMI-1 significantly improved lung histology and prevented leukocyte infiltration. Reduced leukocyte recruitment could be explained by reduced production of pro-inflammatory cytokines and lower levels of the endothelial adhesion molecules ICAM-1 and VCAM-1. Additionally, the NLR was significantly reduced by ADAM17 inhibition. Thus, we propose inhibition of ADAM17 as a novel promising treatment strategy in SARS-CoV-2-infected MESHD individuals to prevent the progression towards severe Covid-19 MESHD.

    Quantatitive Analysis of Conserved Sites on the SARS-CoV-2 Receptor-Binding Domain to Promote Development of Universal SARS-Like Coronavirus Vaccines

    Authors: Siling Wang; Dinghui Wu; Hualong Xiong; Juan Wang; Zimin Tang; Zihao Chen; Yizhen Wang; Yali Zhang; Dong Ying; Xue Lin; Chang Liu; Shaoqi Guo; Weikun Tian; Yajie Lin; Xiaoping Zhang; Quan Yuan; Hai Yu; Tianying Zhang; Zizheng Zheng; Ningshao Xia

    doi:10.1101/2021.04.10.439161 Date: 2021-04-11 Source: bioRxiv

    Although vaccines have been successfully developed and approved against SARS-CoV-2, it is still valuable to perform studies on conserved antigenic sites for preventing possible pandemic-risk of other SARS-like coronavirus in the future and prevalent SARS-CoV-2 variants. By antibodies obtained from convalescent COVID-19 MESHD individuals, receptor binding domain ( RBD MESHD) were identified as immunodominant neutralizing domain that efficiently elicits neutralizing antibody response with on-going affinity mature. Moreover, we succeeded to define a quantitative antigenic map of neutralizing sites within SARS-CoV-2 RBD, and found that sites S2, S3 and S4 (new-found site) are conserved sites and determined as subimmunodominant sites, putatively due to their less accessibility than SARS-CoV-2 unique sites. P10-6G3, P07-4D10 and P05-6H7, respectively targeting S2, S3 and S4, are relatively rare antibodies that also potently neutralizes SARS-CoV MESHD, and the last mAbs performing neutralization without blocking S protein PROTEIN binding to receptor. Further, we have tried to design some RBDs to improve the immunogenicity of conserved sites. Our studies, focusing on conserved antigenic sites of SARS-CoV-2 and SARS-CoV MESHD, provide insights for promoting development of universal SARS-like coronavirus vaccines therefore enhancing our pandemic preparedness.

    Ultrastructural insight into SARS-CoV-2 attachment, entry and budding in human airway epithelium

    Authors: Andreia L Pinto; Ranjit K Rai; Jonathan C Brown; Paul Griffin; James R Edgar; Anand Shah; Aran Singanayagam; Claire Hogg; Wendy S Barclay; Clare E Futter; Thomas Burgoyne

    doi:10.1101/2021.04.10.439279 Date: 2021-04-11 Source: bioRxiv

    Ultrastructural studies of SARS-CoV-2 infected MESHD cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Many studies are limited by the lack of access to appropriate cellular models. As the airway epithelium is the primary site of infection it is essential to study SARS-CoV-2 infection MESHD of these cells. Here, we examined human airway epithelium, grown as highly differentiated air-liquid interface cultures and infected with three different isolates of SARS-CoV-2 including the B.1.1.7 variant (Variant of Concern 202012/01) by transmission electron microscopy and tomography. For all isolates, the virus infected ciliated but not goblet epithelial cells. Two key SARS-CoV-2 entry molecules, ACE2 HGNC and TMPRSS2 HGNC, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistent with these observations, extracellular virions were frequently seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion at the apical plasma membrane demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein PROTEIN-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein PROTEIN. Profiles strongly suggesting viral budding from the membrane was observed in these compartments and this may explain how virions gain their S glycoprotein PROTEIN containing envelope.

    Estimating COVID-19 MESHD infection fatality MESHD rate in Mumbai during 2020

    Authors: Murad Banaji

    doi:10.1101/2021.04.08.21255101 Date: 2021-04-10 Source: medRxiv

    The aim of this piece is to estimate the infection fatality MESHD rate (IFR) of COVID-19 MESHD in Mumbai during 2020, namely the fraction of SARS-CoV-2 infections MESHD which resulted in death. The estimates are based on the city's seroprevalence and fatality data. This task runs into difficulties connected with obtaining reliable estimates of both the numerator (fatalities) and the denominator (infections). In the light of the many uncertainties, it makes most sense to present a range of values with transparent discussion of assumptions and possible biases. We find that the estimates are consistent with meta-analyses of COVID-19 MESHD age-stratified IFR.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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