Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (108)

ProteinN (28)

NSP5 (11)

ComplexRdRp (10)

ProteinE (7)


SARS-CoV-2 Proteins
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    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.

    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.

    Genome-wide CRISPR activation screen identifies novel receptors for SARS-CoV-2 entry MESHD

    Authors: Shiyou Zhu; Ying Liu; Zhuo Zhou; Zhiying Zhang; Xia Xiao; Zhiheng Liu; Ang Chen; Xiaojing Dong; Feng Tian; Shihua Chen; Yiyuan Xu; Chunhui Wang; Qiheng Li; Xuran Niu; Qian Pan; Shuo Du; Junyu Xiao; Jianwei Wang; Wensheng Wei

    doi:10.1101/2021.04.08.438924 Date: 2021-04-09 Source: bioRxiv

    The ongoing pandemic of coronavirus disease 2019 MESHD ( COVID-19 MESHD) caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has been endangering worldwide public health and economy. SARS-CoV-2 infects MESHD a variety of tissues where the known receptor ACE2 HGNC is low or almost absent, suggesting the existence of alternative pathways for virus entry. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection MESHD. In addition to known host proteins, i.e PROTEIN. ACE2 HGNC, TMPRSS2 HGNC, and NRP1 HGNC, we identified multiple host components, among which LDLRAD3 HGNC, TMEM30A HGNC, and CLEC4G HGNC were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike's N-terminal domain ( NTD HGNC). Their essential and physiological roles have all been confirmed in either neuron or liver cells. In particular, LDLRAD3 HGNC and CLEC4G HGNC mediate SARS-CoV-2 entry MESHD and infection in a fashion independent of ACE2 HGNC. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of the therapeutic countermeasures against COVID-19 MESHD.

    The association of ABO blood group HGNC with the asymptomatic COVID-19 MESHD cases in India

    Authors: Prajjval Pratap Singh; Abhishek K Srivastava; Sudhir K Upadhyay; Ashish Singh; Pranav Gupta; Sanjeev Maurya; Shashank Upadhyay; Rudra K Pandey; Anshika Shrivastava; Priya Dev; Vanya Singh; Rahul Mishra; Manoj K Shukla; Govind Chaubey; Pradeep Kumar; Vandana Rai; Yamini B Tripathy; Abhishek Pathak; Vijaya N Mishra; Chandana Basu Mallick; Panjak Shrivastava; Gyaneshwer Chaubey

    doi:10.1101/2021.04.01.21254681 Date: 2021-04-06 Source: medRxiv

    The COVID-19 pandemic MESHD has resulted several waves of infection in many countries worldwide. The large variations in case fatality ratio among different geographical regions suggests that the human susceptibility against this virus varies substantially. Several studies from different parts of the world showed a significant association of ABO blood group HGNC and COVID-19 MESHD susceptibility. It was shown that individuals with blood group O are at the lower risk of coronavirus infection MESHD. To establish the association of ABO blood group HGNC in SARS-CoV-2 susceptibility, we for the first time analysed SARS-CoV-2 neutralising antibodies as well as blood groups among 509 random individuals from three major districts of Eastern Uttar Pradesh region of India. . Interestingly, we found neutralising antibodies in significantly higher percentage of people with blood group AB (0.36) followed by B (0.31), A (0.22) and lowest in people with blood group O (0.11). This indicates that people with blood group AB are at comparatively higher risk of infection than other blood groups. Further, in line to previous reports we too observed that people with blood group O have significantly decreased risk of SARS-CoV-2 infection MESHD. Thus, among the asymptomatic SARS-CoV-2 infected MESHD individuals with blood group AB has highest, whilst blood group O has lowest risk of infection.

    Substitutions and codon usage in SARS-CoV-2 in mammals indicate natural selection and host adaptation

    Authors: Zhixiong Lei Sr.; Dan Zhang Sr.; Long Liu

    doi:10.1101/2021.04.04.438417 Date: 2021-04-05 Source: bioRxiv

    The outbreak of COVID-19 MESHD, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD, rapidly spread to create a global pandemic and has continued to spread across hosts from humans to animals, transmitting particularly effectively in mink. How SARS-CoV-2 evolves in animals and humans and the differences in the separate evolutionary processes remain unclear. We analyzed the composition and codon usage bias of SARS-CoV-2 MESHD in infected humans and animals. Compared with other animals, SARS-CoV-2 in mink had the most substitutions. The substitutions of cytidine in SARS-CoV-2 in mink account for nearly 50% of the substitutions, while those in other animals represent only 30% of the substitutions. The incidence of adenine transversion in SARS-CoV-2 in other animals is threefold higher than that in mink-CoV (the SARS-CoV-2 virus in mink). A synonymous codon usage analysis showed that SARS-CoV-2 is optimized to adapt in the animals in which it is currently reported, and all of the animals showed decreased adaptability relative to that of humans, except for mink. A binding affinity analysis indicated that the spike protein PROTEIN of the SARS-CoV-2 variant in mink showed a greater preference for binding with the mink receptor ACE2 than with the human receptor, especially as the mutation Y453F and F486L in mink-CoV lead to improvement of binding affinity for mink receptor. Our study focuses on the divergence of SARS-CoV-2 genome composition and codon usage in humans and animals, indicating possible natural selection and current host adaptation.

    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.

    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.

    ACE HGNC gene variants rise the risk of severe COVID-19 MESHD in patients with hypertension MESHD, dyslipidemia MESHD or diabetes MESHD. A pilot study

    Authors: María Íñiguez; Patricia Pérez-Matute; Pablo Villoslada-Blanco; Emma Recio-Fernandez; Diana Ezquerro-Perez; Jorge Alba; M.Lourdes Ferreira-Laso; José A. Oteo

    doi:10.1101/2021.03.24.21253576 Date: 2021-03-26 Source: medRxiv

    Coronavirus disease MESHD 19 ( COVID-19 MESHD) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD continues to scale and threaten human health and public safety. It is essential to identify those risk factors that lead to a poor prognosis of the disease. A predisposing host genetic background could be one of these factors that explain the interindividual variability to COVID-19 MESHD severity. Thus, we have studied whether the rs4341 and rs4343 polymorphisms of the angiotensin converting enzyme HGNC ( ACE HGNC) gene, key regulator of the renin-aldosterone-angiotensin system (RAAS), could explain the different outcomes of 128 COVID-19 MESHD patients with diverse degree of severity (33 asymptomatic or mildly asymptomatic, 66 hospitalized in the general ward, and 29 admitted to the ICU). We found that G allele of rs4341 and rs4343 was associated with severe COVID-19 MESHD in hypertensive MESHD patients, independently of gender (p<0.05). G-carrier genotypes of both polymorphisms were also associated with higher mortality (p< 0.05) and higher severity of COVID-19 MESHD in dyslipidemic (p<0.05) and type 2 diabetic MESHD patients (p< 0.01). In conclusion, our preliminary study suggests that the G-containing genotypes of rs4341 and rs4343 confer an additional risk of adverse COVID-19 MESHD prognosis. Thus, rs4341 and rs4343 polymorphisms of ACE HGNC could be predictive markers of severity of COVID-19 MESHD in those patients with hypertension MESHD, dyslipidemia MESHD or diabetes MESHD. The knowledge of these genetic data could contribute to precision management of SARS-Cov2 infected MESHD patients when admitted to hospital.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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