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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (289)

ProteinN (99)

NSP5 (59)

ComplexRdRp (26)

NSP3 (17)


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    XAV-19, a novel swine glyco-humanized polyclonal antibody against SARS-CoV-2 spike PROTEIN, efficiently neutralizes B.1.1.7 British and B.1.351 South-African variants.

    Authors: Bernard Vanhove; Benjamin Gaborit; Gwenaelle Evanno; Carine Ciron; Pierre-Joseph Royer; Elsa Lheriteau; Soline Denie; Francois Raffi; Odile Duvaux

    doi:10.1101/2021.04.02.437747 Date: 2021-04-05 Source: bioRxiv

    Amino acid substitutions and deletions in spike (S) protein PROTEIN of the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein PROTEIN, through the recognition of multiple target epitopes, have the potential to maintain neutralization capacities. We report on XAV-19, a swine glyco-humanized polyclonal antibody (GH-pAb) raised against the receptor binding domain (RBD) of the Wuhan-Hu-1 spike protein PROTEIN of SARS-CoV-2. XAV-19 target epitopes are distributed all over the RBD and particularly cover the receptor binding motives (RBM), on direct contact sites with the Angiotensin Converting Enzyme-2 (ACE-2). Using spike/ACE2 interaction assays, we analyzed in vitro the impact of punctual and grouped mutations in the S protein PROTEIN corresponding to the B.1.1.7 (British form; UK) and B.1.351 (South-African form, SA) variants and recorded that neutralization by XAV-19 exhibited little if any sensitivity to these mutations. These results were confirmed by two independent tissue culture infective doses assays (TCID) showing 100% neutralization of the variants at close concentrations. XAV-19, which is currently evaluated in patients hospitalized for coronavirus disease 2019 MESHD ( Covid-19 MESHD) in the phase 2a-2b of the POLYCOR study (ClinicalTrial.gov, NCT04453384), may provide a novel effective therapeutic tool to combat coronavirus disease 2019 MESHD ( Covid-19 MESHD), caused by the original Wuhan form and by the UK/SA variants of concern.

    Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 MESHD golden Syrian hamster model

    Authors: Santosh Dhakal; Camilo A. Ruiz-Bedoya; Ruifeng Zhou; Patrick Creisher; Jason Villano; Kirsten Littlefield; Jennie Castillo; Paula Marinho; Anne Jedlicka; Alvaro Ordonez; Natalia Majewska; Michael Betenbaugh; Kelly Flavahan; Alice Mueller; Monika Looney; Darla Quijada; Filipa Mota; Sarah E. Beck; Jacqueline K Brockhurst; Alicia Braxton; Natalie Castell; Kelly A. Metcalf Pate; Petros C. Karakousis; Joseph L. Mankowski; Andrew Pekosz; Sanjay K Jain; Sabra L. Klein

    doi:10.1101/2021.04.02.438292 Date: 2021-04-04 Source: bioRxiv

    In the ongoing coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) MESHD, more severe outcomes are reported in males compared with females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of SARS-CoV-2. Adult male and female golden Syrian hamsters (8-10 weeks of age) were inoculated intranasally with 105 TCID50 of SARS-CoV-2/USA-WA1/2020 and euthanized at several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the infectious virus has been cleared) phases of infection. There was no mortality, but infected male hamsters experienced greater morbidity, losing a greater percentage of body mass, developing more extensive pneumonia MESHD as noted on chest computed tomography, and recovering more slowly than females. Treatment of male hamsters with estradiol did not alter pulmonary damage MESHD. Virus titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary cytokine concentrations, including IFNb and TNFa, were comparable between the sexes. However, during the recovery phase of infection, females mounted two-fold greater IgM, IgG, and IgA responses against the receptor-binding domain of the spike protein (S PROTEIN-RBD) in both plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies against whole inactivated SARS-CoV-2 and mutant S-RBDs MESHD, as well as virus neutralizing antibodies in plasma. The development of an animal model to study COVID-19 MESHD sex differences will allow for a greater mechanistic understanding of the SARS-CoV-2 associated sex differences seen in the human population.

    Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways

    Authors: Ke Xu; Xingyi Shi; Chris Husted; Rui Hong; Yichen Wang; Boting Ning; Travis Sullivan; Kimberly M Rieger-Christ; Fenghai Duan; Helga Marques; Adam C Gower; Xiaohui Xiao; Hanqiao Liu; Gang Liu; Grant Duclos; Avrum Spira; Sarah A Mazzilli; Ehab Billatos; Marc E Lenburg; Joshua D Campbell; Jennifer Beane

    doi:10.1101/2021.03.30.21254564 Date: 2021-04-04 Source: medRxiv

    Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) is caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), which infects host cells with help from the Viral Entry (VE) proteins ACE2 HGNC, TMPRSS2 HGNC, and CTSL HGNC. Proposed risk factors for viral infection MESHD, as well as the rate of disease progression, include age, sex, chronic obstructive pulmonary disease MESHD, cancer MESHD, and cigarette smoking. To investigate whether the proposed risk factors increase viral infection MESHD by modulation of the VE genes, we examined gene expression profiles of 796 nasal and 1,673 bronchial samples across four lung cancer MESHD screening cohorts containing individuals without COVID-19 MESHD. Smoking was the only clinical factor reproducibly associated with the expression of any VE gene across cohorts. ACE2 HGNC expression was significantly up-regulated with smoking in the bronchus but significantly down-regulated with smoking in the nose. Furthermore, expression of individual VE genes were not correlated between paired nasal and bronchial samples from the same patients. Single-cell RNA-seq of nasal brushings revealed that an ACE2 HGNC gene module was detected in a variety of nasal secretory cells with the highest expression in the C15orf48 HGNC+ secretory cells, while a TMPRSS2 HGNC gene module was most highly expressed in nasal keratinizing epithelial cells. In contrast, single-cell RNA-seq of bronchial brushings revealed that ACE2 HGNC and TMPRSS2 HGNC gene modules were most enriched in MUC5AC HGNC+ bronchial goblet cells. The CTSL HGNC gene module was highly expressed in immune populations of both nasal and bronchial brushings. Deconvolution of bulk RNA-seq showed that the proportion of MUC5AC HGNC+ goblet cells was increased in current smokers in both the nose and bronchus but proportions of nasal keratinizing epithelial cells, C15orf48 HGNC+ secretory cells, and immune cells were not associated with smoking status. The complex association between VE gene expression and smoking in the nasal and bronchial epithelium revealed by our results may partially explain conflicting reports on the association between smoking and SARS-CoV-2 infection MESHD.

    Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike PROTEIN variants

    Authors: Satoshi Ikegame; Mohammed N. A. Siddiquey; Chuan-Tien Hung; Griffin Haas; Luca Brambilla; Kasopefoluwa Y. Oguntuyo; Shreyas Kowdle; Ariel Esteban Vilardo; Alexis Edelstein; Claudia Perandones; Jeremy P. Kamil; Benhur Lee

    doi:10.1101/2021.03.31.21254660 Date: 2021-04-02 Source: medRxiv

    The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia MESHD outbreak in Wuhan, China. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 variants of concern (VOC) across diverse geographic locales suggests herd immunity may fail to eliminate the virus. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus MESHD ( VSV MESHD) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV MESHD-G, coupled with a clonal HEK-293T ACE2 HGNC TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that 8 out of 12 (75%) of serum samples from 12 recipients of the Russian Sputnik V Ad26 / Ad5 vaccine showed dose response curve slopes indicative of failure to neutralize rcVSV-CoV2-S: B.1.351. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of emergent SARS-CoV-2 variants may benefit from updated vaccines.

    A realistic touch-transfer method reveals low risk of transmission for SARS-CoV-2 by contaminated coins and bank notes

    Authors: Daniel Todt; Toni Luise Meister; Barbora Tamele; John Howes; Dajana Paulmann; Britta Becker; Florian H. Brill; Mark Wind; Jack Schijven; Baxolele Mhlekude; Christine Goffinet; Adalbert Krawczyk; Joerg Steinmann; Stepanie Pfaender; Yannick Brueggemann; Eike Steinmann

    doi:10.1101/2021.04.02.438182 Date: 2021-04-02 Source: bioRxiv

    The current severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) pandemic has created a significant threat to global health. While respiratory aerosols or droplets are considered as the main route of human-to-human transmission, secretions expelled by infected individuals can also contaminate surfaces and objects, potentially creating the risk of fomite-based transmission. Consequently, frequently touched objects such as paper currency and coins have been suspected as a potential transmission vehicle. To assess the risk of SARS-CoV-2 transmission by banknotes and coins, we examined the stability of SARS-CoV-2 and bovine coronavirus (BCoV), as surrogate with lower biosafety restrictions, on these different means of payment and developed a touch transfer method to examine transfer efficiency from contaminated surfaces to skin. Although we observed prolonged virus stability, our results, including a novel touch transfer method, indicate that the transmission of SARS-CoV-2 via contaminated coins and banknotes is unlikely and requires high viral loads and a timely order of specific events.

    Emerging SARS-CoV-2 mutation hotspots associated with clinical outcomes

    Authors: Xianwu Pang; Pu Li; Lifeng Zhang; Lusheng Que; Min Dong; Qihui Wang; Yinfeng Wei; Bo Xie; Xing Xie; Lanxiang Li; Chunyue Yin; Liuchun Wei; Qingniao Zhou; Yingfang Li; Lei Yu; Weidong Li; Zengnan Mo; Jing Leng; Yanling Hu

    doi:10.1101/2021.03.31.437666 Date: 2021-03-31 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the cause of the ongoing coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes and related factors is critical for treatment and prevention. Here, we analyzed 209,551 high-coverage complete virus sequences and 321 RNA-seq samples to mine the mutations associated with clinical outcome in the SARS-CoV-2 genome. Several important hotspot variants were found to be associated with severe clinical outcomes. Q57H variant in ORF3a PROTEIN protein were found to be associated with higher mortality rate, and was high proportion in severe cases (39.36%) and 501Y.V2 strains (100%) but poorly proportional to asymptomatic cases (10.04%). T265I could change nsp2 HGNC structure and mitochondrial permeability, and evidently higher in severe cases (20.12%) and 501Y.V2 strains (100%) but lower in asymptomatic cases (1.43%). Additionally, R203K and G204R could decrease the flexibility and immunogenic property of N protein PROTEIN with high frequency among severe cases, VUI 202012/01 and 484K.V2 strains. Interestingly, the SARS-CoV-2 genome was more susceptible to mutation because of the high frequency of nt14408 mutation (which located in RNA polymerase) and the high expression levels of ADAR HGNC and APOBEC in severe clinical outcomes. In conclusion, several important mutation hotspots in the SARS-CoV-2 genome associated with clinical outcomes was found in our study, and that might correlate with different SARS-CoV-2 mortality rates.

    Prevalence of anti-SARS-CoV-2 antibodies in Poznan, Poland, after the first wave of the COVID-19 pandemic MESHD

    Authors: Dagny Lorent; Rafal Nowak; Carolina Roxo; Elzbieta Lenartowicz; Aleksandra Makarewicz; Bartosz Zaremba; Szymon Nowak; Lukasz Kuszel; Jerzy Stefaniak; Ryszard Kierzek; Pawel Zmora

    doi:10.1101/2021.03.29.21254544 Date: 2021-03-31 Source: medRxiv

    A serosurvey of antibodies against severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) was performed between July and September 2020. Within this study, we found that 0.93% of the Poznan metropolitan area population had been exposed to SARS-CoV-2 after the first wave of coronavirus disease 2019 MESHD ( COVID-19 MESHD).

    Linking Diabetes mellitus MESHD to SARS-CoV-2 infection MESHD through differential targeting of the microRNAs in the Pancreas tissue MESHD

    Authors: Bhavya; Ekta Pathak; Rajeev Mishra

    doi:10.1101/2021.03.31.437823 Date: 2021-03-31 Source: bioRxiv

    Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) severity and Diabetes mellitus MESHD affect each other bidirectionally. The plus-sense single-stranded RNA (+ssRNA) genome of the SARS-CoV-2 virus can be targeted and suppressed by the host cell's microRNAs (miRNAs). Using the differential gene expression analysis between the mock-infected and the SARS-CoV-2-infected pancreatic MESHD tissue, we report five Diabetes MESHD-associated genes that are upregulated due to SARS-CoV-2 infection MESHD in the hESC pancreas tissues. Ten miRNAs regulating these five genes can potentially target the SARS-CoV-2 genome. We hypothesize that the SARS-CoV-2 genome copies in the infected human pancreas cell compete with the host cell native genes in being regulated by the native miRNAs. It leads to the reduced miRNA-regulation and, thus, the upregulation of the Diabetes MESHD-associated native genes. Thus, the resultant new-onset or elevated Diabetic symptoms MESHD may worsen the condition of COVID-19 MESHD patients.

    Targeting the Microbiome With KB109 in Outpatients with Mild to Moderate COVID-19 MESHD Reduced Medically Attended Acute Care Visits and Improved Symptom Duration in Patients With Comorbidities

    Authors: John P Haran; Yan Zheng; Katharine Knobil; Norma Alonzo-Palma; Jonathan Lawrence; Mark Wingertzahn

    doi:10.1101/2021.03.26.21254422 Date: 2021-03-29 Source: medRxiv

    Introduction In 2020, the world experienced the beginning of the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), also known as the coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic. Mounting evidence indicates that the gut microbiome plays a role in host immune response to infections and, in turn, may have an impact on the disease trajectory of SARS-CoV2 infection MESHD. However, it remains to be established whether modulation of the microbiome can impact COVID-19 MESHD-related symptomatology and patient outcomes. Therefore, we conducted a study designed to modulate the microbiome evaluating the safety and physiologic effects of KB109 combined with self-supportive care (SSC) vs SSC alone in non-hospitalized patients with mild to moderate COVID-19 MESHD. KB109 is a novel synthetic glycan developed to increase the production of gut microbial metabolites that support immune system homeostasis through gut microbiome modulation. Our goal was to gain a better understanding of the safety of KB109, the natural course of COVID-19 MESHD symptomatology, and the possible role of the gut microbiome in patients with mild to moderate COVID-19 MESHD. Methods Adult patients who tested positive for COVID-19 MESHD were randomized 1:1 to receive KB109 combined with SSC or SSC alone for 14 days and were then followed for an additional 21 days (35 days in total). Patients self-assessed their COVID-19 MESHD-related symptoms (8 cardinal symptoms plus 5 additional symptoms) and self-reported comorbidities. The primary and secondary objectives were to evaluate the safety of KB109 plus SSC compared with that of SSC alone and to evaluate selected measures of health, respectively. Results Between July 2, 2020 and December 23, 2020, 350 patients were randomized to receive KB109 and SSC (n=174) or SSC alone (n=176). Overall, the most common comorbidities reported were hypertension MESHD (18.0% [63/350 patients]) followed by chronic lung disease MESHD (8.6% 30/350 patients). KB109 was well tolerated with most treatment-emergent adverse events being mild to moderate in severity. The administration of KB109 plus SSC reduced medically-attended visits (ie, hospitalization, emergency room visits, or urgent care visits) by 50.0% in the overall population and by 61.7% in patients with [≥]1 comorbidity; in patients aged [≥]45 years or with [≥]1 comorbidity, medically-attended visits were reduced by 52.8%, In the SSC group, patients reporting [≥]1 comorbidity had a longer median time to resolution of symptoms than those who reported no comorbidities at baseline (13 overall symptoms: 30 vs 21 days, respectively; hazard ratio [HR]=1.163 [95% CI, 0.723-1.872]; 8 cardinal symptoms: 21 vs 15 days, respectively; HR=1.283 [95% CI, 0.809-2.035]). In patients reporting [≥]1 comorbidity, median time to resolution of symptoms was shorter in the KB109 plus SSC group compared with the SSC alone group (13 overall symptoms: 30 vs 21 days, respectively; HR=1.422 [95% CI, 0.898-2.250]; 8 cardinal symptoms: 17 vs 21 days, respectively; HR=1.574 [95% CI, 0.997-2.485]). In the KB109 plus SSC group, patients aged [≥]45 years or with [≥]1 comorbidity had a shorter median time to resolution of symptoms compared with SSC alone (overall 13 symptoms: 21 vs 31 days; HR=1.597 [95% CI, 1.064-2.398]). Conclusions Results from our study show that KB109 is well tolerated among patients with mild to moderate COVID-19 MESHD. Patients with [≥]1 comorbidity had a longer duration of COVID-19 MESHD symptoms than those without comorbidities. Moreover, in patients reporting [≥]1 comorbidity or aged [≥]45 years (at-risk population), administration of KB109 plus SSC improved median time to resolution of COVID-19 MESHD-related symptoms and reduced the rate of medically-attended visits compared with SSC alone.

    Modeling Substrate Coordination to Zn-Bound Angiotensin Converting Enzyme HGNC 2

    Authors: Peter R. Fatouros; Urmi Roy; Shantanu Sur

    doi:10.1101/2021.03.27.437352 Date: 2021-03-29 Source: bioRxiv

    The spike protein PROTEIN in the envelope of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) interacts with the receptor Angiotensin Converting Enzyme 2 (ACE2) on the host cell to facilitate the viral uptake. Angiotensin II HGNC (Ang II) peptide, which has a naturally high affinity for ACE2, may be useful in inhibiting this interaction. In this study, we computationally designed several Ang II mutants to find a strong binding sequence to ACE2 receptor and examined the role of ligand substitution in the docking of native as well as mutant Ang II to the ACE2 receptor. The peptide in the ACE2-peptide complex was coordinated to zinc in the ACE2 cleft. Exploratory molecular dynamics ( MD MESHD) simulations were used to measure the time-based stability of the native and mutant peptides and their receptor complexes. The MD-generated root-mean-square deviation (RMSD) values are mostly similar between the native and seven mutant peptides considered in this work, although the values for free peptides demonstrated higher variation, and often were higher in amplitude than peptides associated with the ACE2 complex. An observed lack of a strong secondary structure in the short peptides is attributed to the latter's greater flexibility and movement. The strongest binding energies within the ACE2-peptide complexes were observed in the native Ang II and only one of its mutant variants, suggesting ACE2 cleft is designed to provide optimal binding to the native sequence. An examination of the S1 binding site on ACE2 suggests that complex formation alone with these peptides may not be sufficient to allosterically inhibit the binding of SARS-CoV-2 spike PROTEIN proteins. However, it opens up the potential for utilizing AngII-ACE2 binding in the future design of molecular and supramolecular structures to prevent spike protein PROTEIN interaction with the receptor through creation of steric hindrance.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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