Corpus overview


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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (654)

ProteinN (149)

NSP5 (75)

ComplexRdRp (46)

ProteinE (43)


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SARS-CoV-2 Proteins
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    Short-term antibody response and tolerability of one dose of BNT162b2 vaccine in patients receiving hemodialysis

    Authors: Remi Goupil; Mehdi Benlarbi; William Beaubien-Souligny; Annie-Claire Nadeau-Fredette; Chatterjee Debashree; Guillaume Goyette; Caroline Lamarche; Andrés Finzi; Rita S Suri

    doi:10.1101/2021.03.30.21254652 Date: 2021-04-01 Source: medRxiv

    Background: Patients with end-stage kidney disease MESHD receiving in-center hemodialysis are at high risk of exposed to, and dying from, SARS-CoV-2. As impairments in both humoral and cellular immunity are common in this population, their response to vaccination against SARS-CoV-2 is uncertain. Methods: We have followed in-center hemodialysis patients in the Reseau Renal Quebecois MESHD since March 2020 with serial PCRs for COVID-19 MESHD and clinical outcomes. Plasma samples were taken from 58 patients from one center before, and 4 weeks after, vaccination with one dose of the BNT162b2 mRNA vaccine. Anti-RBD (region binding domain of the SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN protein) IgG levels were measured using ELISA and compared to levels in 32 health care worker (HCW) controls, as well as levels in convalescent plasma taken from 12 hemodialysis patients 4-12 weeks after COVID-19 MESHD infection. Patients were stratified based on evidence of previous infection with COVID-19 MESHD (positive PCR or antiRBD detectable at baseline). Results: Compared with health-care workers, hemodialysis patients without prior COVID-19 MESHD exhibited significantly lower anti-RBD IgG levels 4 weeks after vaccination (p=0.0007). Anti-RBD IgG was non-detectable in 1/16 (6%) of HCWs, and 25/46 (54%) of dialysis patients (p=0.0008). In dialysis patients previously infected with COVID-19 MESHD, mean anti-RBD levels were significantly lower than their HCW controls (p=0.0031), but not signficantly different than those in convalescent plasma of recently infected dialysis patients (p=NS). No patients reported any symptoms 7 days after vaccination on a standardized questionnaire. Conclusion: The BNT162b2 vaccine was well-tolerated in hemodialysis patients, but failed to elicit a humoral immune response in >50% patients by 4 weeks. Whether these patients develop antibodies or T-cell responses after prolonged observation requires further study. Until then, we recommend that rigorous infection MESHD prevention and control measures in the dialysis unit and outside of it be continued to prevent SARS-CoV-2 infection MESHD in this susceptible population.

    Screening of HLA-A HGNC restricted T cell epitopes of SARS-CoV-2 and induction of CD8+ T cell responses in HLA-A HGNC transgenic mice

    Authors: Xiaoxiao Jin; Yan Ding; Shihui Sun; Xinyi Wang; Zining Zhou; Xiaotao Liu; Miaomiao Li; Xian Chen; Anran Shen; Yandan Wu; Bicheng Liu; Jianqiong Zhang; Jian Li; Yi Yang; Haibo Qiu; Chuanlai Shen; Yuxian He; Guangyu Zhao

    doi:10.1101/2021.04.01.438020 Date: 2021-04-01 Source: bioRxiv

    While SARS-CoV-2-specific T cells have been characterized to play essential roles in host immune protection in COVID-19 MESHD patients, few researches focus on the functional validation of T cell epitopes and development of vaccines inducing specific T cell responses. In this study, 120 CD8 T cell epitopes from E, M, N, S and RdRp PROTEIN proteins of SARS-CoV-2 were validated by on-silicon prediction, DC-peptide-PBL costimulation with PBMCs of healthy donors and HLA-A HGNC molecule competitive binding experiments. Among them, 110, 15, 6, 14 and 12 epitopes were highly homologous with SARS-CoV MESHD, OC43, NL63, HKU1, and 229E, respectively. Thirty-one epitopes restricted by HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C), R848 or polylactic-co-glycolic acid nanoparticles, which elicited robust specific CD8 T cell responses in wild-type and HLA-A2/DR1 transgenic mice. Seven of the 31 epitopes were found to be cross-presented by HLA-A2 and H-2K/Db molecules. These data have provided a library of SARS-CoV-2 CD8 T cell epitopes which restricted by a series of high-frequency HLA-A HGNC allotypes and covered broad population in Asia, and initially confirmed the feasibility of human MHC class I molecule-restricted SARS-CoV2 epitope peptide cocktail vaccines, thus will facilitate the development of T cell epitope vaccines and specific cellular function detection kits.

    Coagulation factors directly cleave SARS-CoV-2 spike PROTEIN and enhance viral entry MESHD

    Authors: Edward R Kastenhuber; Javier A. Jaimes; Jared L. Johnson; Marisa Mercadante; Frauke Muecksch; Yiska Weisblum; Yaron Bram; Robert E. Schwartz; Gary R. Whittaker; Lewis C. Cantley

    doi:10.1101/2021.03.31.437960 Date: 2021-04-01 Source: bioRxiv

    Coagulopathy is recognized as a significant aspect of morbidity in COVID-19 MESHD patients. The clotting cascade is propagated by a series of proteases, including factor Xa HGNC and thrombin HGNC. Other host proteases, including TMPRSS2 HGNC, are recognized to be important for cleavage activation of SARS-CoV-2 spike PROTEIN to promote viral entry. Using biochemical and cell-based assays, we demonstrate that factor Xa HGNC and thrombin HGNC can also directly cleave SARS-CoV-2 spike PROTEIN, enhancing viral entry. A drug-repurposing screen identified a subset of protease inhibitors that promiscuously inhibited spike cleavage by both transmembrane serine proteases as well as coagulation factors. The mechanism of the protease inhibitors nafamostat and camostat extend beyond inhibition of TMPRSS2 HGNC to coagulation-induced spike cleavage. Anticoagulation is critical in the management of COVID-19 MESHD, and early intervention could provide collateral benefit by suppressing SARS-CoV-2 viral entry. We propose a model of positive feedback whereby infection-induced hypercoagulation MESHD exacerbates SARS-CoV-2 infectivity MESHD.

    Structural dynamics of the β-coronavirus Mpro PROTEIN protease ligand binding sites

    Authors: Eunice Cho; Margarida Rosa; Ruhi Anjum; Saman Mehmood; Mariya Soban; Moniza Mujtaba; Khair Bux; Sarath Chandra Dantu; Alessandro Pandini; Junqi Yin; Heng Ma; Arvind Ramanathan; Barira Islam; Antonia Mey; DEBSINDHU BHOWMIK; Shozeb Haider

    doi:10.1101/2021.03.31.437918 Date: 2021-04-01 Source: bioRxiv

    {beta}-coronaviruses alone have been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a back-up against the emergence of lethal viral variants. One such target is the main protease PROTEIN ( Mpro PROTEIN) that plays an indispensible role in viral replication. The availability of over 270 Mpro PROTEIN X-ray structures in complex with inhibitors provides unique insights into ligand-protein interactions. Herein, we provide a comprehensive comparison of all non-redundant ligand-binding sites available for SARS-CoV2, SARS-CoV MESHD and MERS-CoV Mpro PROTEIN. Extensive adaptive sampling has been used to explore conformational dynamics employing convolutional variational auto encoder-based deep learning, and investigates structural conservation of the ligand binding sites using Markov state models across {beta}-coronavirus homologs. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across {beta}-coronavirus homologs. This highlights the complexity in targeting all three Mpro PROTEIN enzymes with a single pan inhibitor.

    Ultrapotent bispecific antibodies neutralize emerging SARS-CoV-2 variants

    Authors: Hyeseon Cho; Kristina Kay Gonzales-Wartz; Deli Huang; Meng Yuan; Mary Peterson; Janie Liang; Nathan Beutler; Jonathan L. Torres; Yu Cong; Elena Postnikova; Sandhya Bangaru; Chloe Adrienna Talana; Wei Shi; Eun Sung Yang; Yi Zhang; Kwanyee Leung; Lingshu Wang; Linghang Peng; Jeff Skinner; Shanping Li; Nicholas C. Wu; Hejun Liu; Cherrelle Dacon; Thomas Moyer; Melanie Cohen; Ming Zhao; F. Eun-Hyung Lee; Rona S Weinberg; Iyadh Douagi; Robin Gross; Connie Schmaljohn; Amarendra Pegu; John R. Mascola; Michael Holbrook; David Nemazee; Thomas F. Rogers; Andrew B. Ward; Ian A. Wilson; Peter D. Crompton; Joshua Tan

    doi:10.1101/2021.04.01.437942 Date: 2021-04-01 Source: bioRxiv

    The emergence of SARS-CoV-2 variants that threaten the efficacy of existing vaccines and therapeutic antibodies underscores the urgent need for new antibody-based tools that potently neutralize variants by targeting multiple sites of the spike protein PROTEIN. We isolated 216 monoclonal antibodies targeting SARS-CoV-2 from plasmablasts and memory B cells of COVID-19 MESHD patients. The three most potent antibodies targeted distinct regions of the RBD, and all three neutralized the SARS-CoV-2 variants B.1.1.7 and B.1.351. The crystal structure of the most potent antibody, CV503, revealed that it binds to the ridge region of SARS-CoV-2 RBD MESHD, competes with the ACE2 receptor, and has limited contact with key variant residues K417, E484 and N501. We designed bispecific antibodies by combining non-overlapping specificities and identified five ultrapotent bispecific antibodies that inhibit authentic SARS-CoV-2 infection MESHD at concentrations of <1 ng/mL. Through a novel mode of action three bispecific antibodies cross-linked adjacent spike proteins PROTEIN using dual NTD/RBD specificities. One bispecific antibody was >100-fold more potent than a cocktail of its parent monoclonals in vitro and prevented clinical disease in a hamster model at a 2.5 mg/kg dose. Notably, six of nine bispecific antibodies neutralized B.1.1.7, B.1.351 and the wild-type virus with comparable potency, despite partial or complete loss of activity of at least one parent monoclonal antibody against B.1.351. Furthermore, a bispecific antibody that neutralized B.1.351 protected against SARS-CoV-2 expressing the crucial E484K mutation in the hamster model. Thus, bispecific antibodies represent a promising next-generation countermeasure against SARS-CoV-2 variants of concern.

    Analysis of glycosylation and disulfide bonding of wild-type SARS-CoV-2 spike PROTEIN glycoprotein

    Authors: Shijian Zhang; Eden P. Go; Haitao Ding; Saumya Anang; John C. Kappes; Heather Desaire; Joseph G. Sodroski

    doi:10.1101/2021.04.01.438120 Date: 2021-04-01 Source: bioRxiv

    The SARS-CoV-2 coronavirus, the etiologic agent of COVID-19 MESHD, uses its spike ( S) glycoprotein PROTEIN anchored in the viral membrane to enter host cells. The S glycoprotein PROTEIN is the major target for neutralizing antibodies elicited by natural infection and by vaccines. Approximately 35% of the SARS-CoV-2 S glycoprotein PROTEIN consists of carbohydrate, which can influence virus infectivity and susceptibility to antibody inhibition. We found that virus-like particles produced by coexpression of SARS-CoV-2 S MESHD, M, E and N proteins PROTEIN contained spike glycoproteins PROTEIN that were extensively modified by complex carbohydrates. We used a fucose-selective lectin to enrich the Golgi-resident fraction of a wild-type SARS-CoV-2 S glycoprotein PROTEIN trimer, and determined its glycosylation and disulfide bond profile. Compared with soluble or solubilized S glycoproteins PROTEIN modified to prevent proteolytic cleavage and to retain a prefusion conformation, more of the wild-type S glycoprotein PROTEIN N-linked glycans are processed to complex forms. Even Asn 234, a significant percentage of which is decorated by high-mannose glycans on soluble and virion S trimers, is predominantly modified in the Golgi by processed glycans. Three incompletely occupied sites of O-linked glycosylation were detected. Viruses pseudotyped with natural variants of the serine/threonine residues implicated in O-linked glycosylation were generally infectious and exhibited sensitivity to neutralization by soluble ACE2 HGNC and convalescent antisera comparable to that of the wild-type virus. Unlike other natural cysteine variants, a Cys15Phe (C15F) mutant retained partial, but unstable, infectivity. These findings enhance our understanding of the Golgi processing of the native SARS-CoV-2 S glycoprotein PROTEIN carbohydrates and could assist the design of interventions.

    SARS-CoV-2 infections MESHD in children and adolescents with rheumatic musculoskeletal diseases MESHD: data from the National Pediatric Rheumatology Database in Germany

    Authors: Claudia Sengler; Sascha Eulert; Martina Niewerth; Kirsten Minden; Gerd Horneff; Jasmin B Kuemmerle-Deschner; Caroline Siemer; Rainer Berendes; Hermann Girschick; Regina Huehn; Michael Borte; Anton Hospach; Wolfgang Emminger; Jakob Peter Armann; Ariane Klein; Tilmann Kallinich

    doi:10.1101/2021.03.28.21254496 Date: 2021-03-31 Source: medRxiv

    Objectives: Due to their underlying disease as well as therapeutic immunosuppression, children and adolescents with rheumatic MESHD and musculoskeletal diseases MESHD ( RMD MESHD) may be at higher risk for a severe course or worse outcome of COVID-19 MESHD, and SARS-CoV2 infection MESHD may trigger a flare of the RMD MESHD. To address these issues, a specific SARS-CoV-2 questionnaire was implemented in the National Pediatric Rheumatology Database (NPRD) in Germany. Methods: Demographic, clinical and treatment data from juvenile patients with RMD MESHD as well as data about SARS-CoV-2 infection MESHD like test date and method, clinical characteristics, disease course, outcome and impact on the disease activity of the RMD documented on this questionnaire were analyzed. Results: From April 17th, 2020, to February 14th, 2021, data were collected from 79 patients (53% female) with RMD MESHD with median age of 14 years, diagnosed with juvenile idiopathic arthritis MESHD (57%), autoinflammatory (23%) and connective tissue disease (8%). Sixty-one patients (77%) received disease-modifying antirheumatic drugs (DMARDs), 43% biologic DMARDs, and 9% systemic glucocorticoids. Sixty patients (76%) developed symptoms of COVID-19 MESHD. Disease severity was mild and outcome was good in the majority of patients. Two patients were hospitalized, one of whom required intensive care and died of cardiorespiratory failure MESHD. In 84% of SARS-CoV-2-positive patients, no relevant increase in disease activity of the RMD MESHD was observed. Conclusions: In our cohort, COVID-19 MESHD in juvenile patients with RMD MESHD under various medications was mild with good outcome in the majority of cases. SARS-CoV-2 infection MESHD does not appear to have a relevant impact on disease activity of the underlying condition.

    Diagnostic Value of Symptoms for Pediatric SARS-CoV-2 Infection MESHD SARS-CoV-2 Infection MESHD in a Primary Care Setting

    Authors: Chien-Hsiang Weng; Wesley Wing Wah Butt; Meredith B Brooks; Claudia Clarke; Helen Jenkins; Sabina D Holland; Silvia S Chiang

    doi:10.1101/2021.03.29.21254600 Date: 2021-03-31 Source: medRxiv

    Purpose To evaluate the diagnostic value of symptoms used in the screening approaches by daycares and schools for identifying children and adolescents with possible SARS-CoV-2 infection MESHD, we designed a large observational study utilizing the data from primary care settings. Methods This cohort study included children and adolescents evaluated in a network of clinics in Rhode Island. Participants were age-stratified: 0-4, 5-11, and 12-17 years. We estimated the sensitivity, specificity, and area under the receiver operating curve (AUC) of individual symptoms and three symptom combinations: a probable case definition published by the Rhode Island Department of Health (RIDOH), and two novel combinations generated by different statistical approaches to maximize sensitivity and AUC. We evaluated the test characteristics of symptom combinations both with and without consideration of COVID-19 MESHD exposure. Results Two-hundred seventeen (39.1%) of 555 participants were SARS-CoV-2-infected MESHD. Fever MESHD was more common among 0-4 years-olds (p=0.002); older children more frequently reported fatigue MESHD (p=0.02) and anosmia or ageusia MESHD (p=0.047). In children >5 years old, anosmia MESHD or ageusia had 94-98% specificity. In all age groups, exposure history most accurately predicted infection. In combination with COVID-19 MESHD exposure history, various symptom combinations had sensitivity >95% but specificity <30%. No individual symptom or symptom combination had AUC [≥]0.70. Conclusions Anosmia or ageusia MESHD in children [≥]5 years old and dyspnea MESHD in children 5-11 years old should raise providers' index of suspicion for COVID-19 MESHD. However, our overall findings underscore the limited diagnostic value of symptoms and the critical need for widely available, efficient testing.

    Efficacy and safety of convalescent plasma and intravenous immunoglobulin in critically ill COVID-19 MESHD patients. A controlled clinical trial.

    Authors: Jose Lenin Beltran Gonzalez; Mario Gonzalez Gamez; Emmanuel Antonio Mendoza Enciso; Ramiro Josue Esparza Maldonado; Daniel Hernandez Palacios; Samuel Duenas Campos; Itzel Ovalle Robles; Mariana Jocelyn Macias Guzman; Andrea Lucia Garcia Diaz; Cesar Mauricio Gutierrez Pena; Ana Lilia Reza Escalera; Maria Teresa Tiscareno Gutierrez; Elba Galvan Guerra; Maria del Rocio Dorantes Morales; Lucila Martinez Medina; Victor Antonio Monroy Colin; Jose Manuel Arreola Guerra

    doi:10.1101/2021.03.28.21254507 Date: 2021-03-31 Source: medRxiv

    Background The proportion of critically ill COVID 19 patients has collapsed hospital care worldwide. The need for alternative therapies for this group of patients is imperative. This study aims to compare the safety and efficacy of convalescent plasma (CP) compared with human immunoglobulin (IVIg) in patients requiring the administration of high oxygen levels or mechanical ventilation. Methods This is a controlled, randomized, open clinical trial of patients with pneumonia MESHD secondary to SARS CoV 2 infection MESHD, that fulfilled criteria for severe or critical disease MESHD. They were randomized in a 1:2 ratio; group 1 was administered IVIg at a dose of 0.3 grams per kilogram of ideal weight, in an 8 hour infusion every 24 hours, for 5 days. Group 2 was administered 200 ml of CP infused in 2 hours, for 2 days. The primary outcomes were duration of hospitalization and mortality at 28 days. Results: One hundred and ninety (190) patients were randomized; 130 to the CP group, and 60 to the IVIg group. Their average age was 58 years (IQR 47 to 72), and most were male (n= 119, 62.6 %). On inclusion, 85.2 % of patients (n=162) were on invasive mechanical ventilation therapy. Overall mortality in all included patients was 53 % (n= 102), with a median follow-up of 14 days (IQI 8 to 26). Mortality at 28 days was 45.2 % (n=86). In the intention to treat analysis, there was no difference between groups neither in mortality on follow up (53.8 vs. 53.3, p =1.0) nor at 28 days (46.2 vs 43 %, p=0.75, Log Rank p = 0.83). Per protocol analysis between treatment groups revealed no difference in mortality throughout hospitalization (51.5 vs 51.4 %, p=1.0) nor after 28 days (42.1 vs 42.87 %, p=0.92 Log Rank p = 0.54). Only 23 patients in the CP group received plasma with detectable anti SARS CoV 2 antibodies. Conclusions: In critically ill MESHD patients or on invasive mechanical ventilation for treatment of COVID19 MESHD, the use of CP is not superior to IVIg in terms of hospitalization duration or mortality. The use of CP is based on complex logistics and requires an assured level of antibodies if used therapeutically. IVIg does not appear to be useful in this group of patients.

    Upregulated miR-200c HGNC may increase the risk of obese MESHD individuals to severe COVID-19 MESHD

    Authors: Jayanthi Bellae Papannarao; Daryl Schwenke; Patrick J Manning; Rajesh Katare

    doi:10.1101/2021.03.29.21254517 Date: 2021-03-31 Source: medRxiv

    Obesity is a risk factor for coronavirus disease 2019 MESHD ( COVID-19 MESHD) infection, the prevalence of obese MESHD individuals admitted with COVID-19 MESHD ranging between 30 and 60%. Herein we determined whether early changes in microRNAs (miRNAs) could be the underlying molecular mechanism increasing the risk of obese MESHD individuals to COVID-19 MESHD infection. Quantitative real-time PCR analysis of plasma samples for circulating miRNAs showed a significant upregulation of miR-200c HGNC and a small increase in miR HGNC-let-7b obese MESHD individuals. This was associated with significant downregulation of angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC). Both the miRNAs are the direct targets of ACE2 HGNC, the specific functional receptor for severe acute respiratory syndrome coronavirus 2 MESHD. Correlation analysis confirmed a significant negative correlation between ACE2 HGNC and both the miRNAs. Recent studies showed that despite being the functional receptor, inhibition/downregulation of ACE2 HGNC did not reduce the severity of COVID-19 MESHD infection. In contrast, increased angiotensin II HGNC following inhibition of ACE2 HGNC may increase the severity of the disease. Taken together, our novel results identify that upregulation of miR-200c HGNC may increase the susceptibility of obese MESHD individuals to COVID-19 MESHD. Considering miRNA are the earliest molecular regulators, circulating miR-200c HGNC could be a potential biomarker in the early identification of those at the risk of severe COVID-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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