Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (229)

ProteinN (77)

NSP5 (54)

ComplexRdRp (22)

NSP3 (16)


SARS-CoV-2 Proteins
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    Vaccination boosts protective responses and counters SARS-CoV-2-induced pathogenic memory B cells

    Authors: Pankaj K Mishra; Natalie Bruiners; Rahul Ukey; Pratik Datta; Alberta Onyuka; Deborah Handler; Sabiha Hussain; William Honnen; Sukhwinder Singh; Valentina Guerrini; Yue Yin; Hannah Dewald; Alok Choudhary; Daniel B Horton; Emily S Barret; Jason Roy; Stanley H Weiss; Patricia Fitzgerald-Bocarsly; Martin J Blaser; Jeffrey L Carson; Reynold A. Panettieri Jr.; Alfred Lardizabal; Theresa L Chang; Abraham Pinter; Maria L Gennaro

    doi:10.1101/2021.04.11.21255153 Date: 2021-04-14 Source: medRxiv

    Given the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD and the recent implementation of SARS-CoV-2 vaccination, we have much to learn about the duration of immune protection and the interface between the immune responses to infection and to vaccination. To address these questions, we monitored immune responses to SARS-CoV-2 infection MESHD in convalescent individuals over seven months and following mRNA vaccination. Spike Receptor-Binding-Domain (RBD)-specific circulating antibodies and plasma neutralizing activity generally decreased over time, whereas RBD-specific memory B cells persisted. Additionally, using antibody depletion techniques, we showed that the neutralizing activity of plasma specifically resides in the anti-RBD antibodies. More vigorous antibody and B cell responses to vaccination were observed in previously infected subjects relative to uninfected comparators, presumably due to immune priming by infection. SARS-CoV-2 infection MESHD also led to increased numbers of double negative B memory cells, which are described as a dysfunctional B cell subset. This effect was reversed by SARS-CoV-2 vaccination, providing a potential mechanistic explanation for the vaccination-induced reduction in symptoms in patients with "Long-COVID".

    Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants

    Authors: Christy L. Lavine; Shaun Rawson; Haisun Zhu; Krishna Anand; Pei Tong; Avneesh Gautam; Shen Lu; Sarah Sterling; Richard M Walsh Jr.; Jianming Lu; Wei Yang; Michael S Seaman

    doi:10.1101/2021.04.13.439709 Date: 2021-04-14 Source: bioRxiv

    Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) have become the dominant circulating strains that continue to fuel the COVID-19 pandemic MESHD despite intensive vaccination efforts throughout the world. We report here cryo-EM structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Mutations in the B.1.1.7 protein increase the accessibility of its receptor binding domain and also the binding affinity for receptor angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC). The enhanced receptor engagement can account for the increased transmissibility and risk of mortality as the variant may begin to infect efficiently infect MESHD additional cell types expressing low levels of ACE2 HGNC. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein PROTEIN, rendering complete resistance to some potent neutralizing antibodies. These findings provide structural details on how the wide spread of SARS-CoV-2 enables rapid evolution to enhance viral fitness MESHD and immune evasion. They may guide intervention strategies to control the pandemic.

    Detection of SARS-CoV-2 specific IgA in the human milk of COVID-19 MESHD vaccinated, lactating health care workers

    Authors: Vivian Valcarce; Lauren S Stafford; Josef Neu; Nicole Cacho; Leslie Parkier; Martina Mueller; David Burchfield; Nan Li; Joseph Larkin III

    doi:10.1101/2021.04.02.21254642 Date: 2021-04-13 Source: medRxiv

    Importance: In 2019, a deadly virus known as severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), responsible for COVID-19 MESHD, emerged. In December 2020, two mRNA-based COVID-19 MESHD vaccines were approved for use in the United States (US) which provide immunity to those receiving the vaccine. Maternally derived antibodies are a key element of infants' immunity. Certain vaccines given to pregnant and lactating mothers provide immunity to infants through transmission across the placenta, umbilical cord (IgG) and human milk (IgA). Human milk produced by mothers with a history of COVID-19 MESHD infection contains SARS-CoV-2 IgA and IgG. Objective: To determine whether SARS-CoV-2 specific immunoglobulins are found in human milk after the COVID-19 MESHD vaccination, and to characterize the types of immunoglobulins present. Design, setting and participants: This is a prospective observational study conducted at Shands Hospital, University of Florida from December 2020 to March 2021. Twenty-two lactating healthcare workers who received the SARS-CoV-2 mRNA vaccine (Pfizer/BioNtech or Moderna) made up the sample group. Plasma and human milk were collected at three-time points (pre-vaccination, post first vaccine dose , and post-second vaccine dose). SARS-CoV-2 specific IgA and IgG in human milk and in plasma were measured by ELISA. Maternal demographics was compiled. Exposures: Pfizer/BioNtech or Moderna vaccination. Main outcome and measure: Levels of SARS-CoV-2 IgA and IgG in human milk and plasma. Results: We found significant secretion of SARS-CoV-2 specific IgA and IgG in human milk and plasma after SARS-CoV-2 vaccination. Conclusions and relevance: Our results show that the mRNA-based COVID-19 MESHD vaccines induce SARS-CoV-2 specific IgA and IgG secretion in human milk. Further studies are needed to determine the duration of this immune response, its capacity to neutralize the COVID-19 MESHD virus, the transfer of passive immunity to breastfeeding infants, and the potential therapeutic use of human milk IgA to combat SARS-Cov-2 infection MESHDs and COVID-19 MESHD.

    Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease MESHD

    Authors: Michael Sugiyama; Haotian Cui; Mehran Karimzadeh; Edurne Rujas; Hasaan Maan; Sikander Hayat; Kyle Cheung; Rahul Misra; Joseph B. McPhee; Russell D. Viirre; Andrew Haller; Roberto Botelho; Raffi Karshafian; Sarah A. Sabatinos; Gregory D Fairn; Seyed Ali Madani Tonekaboni; Andreas Windemuth; Jean-Philippe Julien; Vijay Shahani; Stephen S. MacKinnon; Bo Wang; Costin N Antonescu

    doi:10.1101/2021.04.13.439274 Date: 2021-04-13 Source: bioRxiv

    The COVID-19 pandemic MESHD has led to an urgent need for the identification of new antiviral drug therapies that can be rapidly deployed to treat patients with this disease. COVID-19 MESHD is caused by infection with the human coronavirus SARS-CoV-2. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of COVID-19 MESHD. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant repurposing drug candidates predicted by the in silico analyses to have antiviral activity against human coronavirus infection MESHD. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection MESHD, which can inform further drug discovery studies.

    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.

    Antibody Response after First-dose of ChAdOx1-nCOV (Covishield) and BBV-152 (Covaxin) amongst Health Care Workers in India: Preliminary Results of Cross-sectional Coronavirus Vaccine-induced Antibody Titre (COVAT) study

    Authors: AWADHESH KUMAR SINGH; Sanjeev Phatak; Nagendra Kumar Singh; Arvind Gupta; Arvind Sharma; Kingshuk Bhattacharjee; RITU SINGH

    doi:10.1101/2021.04.07.21255078 Date: 2021-04-13 Source: medRxiv

    Background: Two vaccines are currently being administered in India to prevent the spread of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). We assessed the humoral immune response after the first dose of two vaccines ChAdOx1-nCOV (CovishieldTM) and BBV-152 (CovaxinTM) in Indian health care workers (HCW). Methods: This ongoing, Pan-India, Cross-sectional, Coronavirus Vaccine-induced Antibody Titre (COVAT) study is being conducted amongst HCW, with or without past history of SARS-CoV-2 infection MESHD. SARS-CoV-2 anti-spike binding antibody is being assessed quantitatively at four timepoints between 21 days or more after the first dose to 6 months after the second dose. Primary aim is to analyze antibody response following each dose of both vaccines and its correlation to age, sex, body mass index (BMI) and comorbidities. Here we report the preliminary results of anti-spike antibody response after the first dose. Results: Amongst the 552 HCW (325 Male, 227 Female), 456 and 96 received first dose of Covishield and Covaxin respectively. Overall, 79.3% showed seropositivity after the first dose. Responder rate and median (IQR) rise in anti-spike antibody was significantly higher in Covishield vs. Covaxin recipient (86.8 vs. 43.8%; 61.5 vs. 6 AU/ml; both p<0.001). This difference persisted in propensity-matched (age, sex and BMI) analysis in 172 subjects. No difference was observed with age, gender and BMI. History of hypertension MESHD had lower responder rate (65.7 vs. 82.3%, p=0.001). Covishield recipient had more adverse event vs. Covaxin arm (46.7 vs. 31.2%, p=0.006). Presence of comorbidities, past SARS-CoV-2 infection MESHD and vaccine types used were independent predictors for seropositivity after the first dose, in multiple logistic regression analysis. Conclusions: While both vaccines elicited immune response, seropositivity rates to anti-spike antibody were significantly higher in Covishield recipient compared to Covaxin after the first dose. Ongoing COVAT study will further enlighten the immune response between two vaccines after the second dose.

    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.

    Development of highly potent neutralising nanobodies against multiple SARS-CoV-2 variants including the variant of concern B.1.351

    Authors: Agnieszka M Sziemel; Shi-Hsia Hwa; Alex Sigal; Grace Tyson; Nicola Logan; Brian J Willett; Peter Joseph Durcan

    doi:10.1101/2021.04.11.439360 Date: 2021-04-12 Source: bioRxiv

    The pathogenic severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has caused a global pandemic. During the years of 2020-2021, millions of humans have died due to SARS-CoV-2 infection MESHD and severe economic damage to the global economy has occurred. Unprecedented rapid investments in vaccine development have been made to counter the spread of SARS-CoV-2 among humans. While vaccines are a key pillar of modern medicine, SARS-CoV-2 has mutated as it spread among humans. Vaccines previously developed and approved by regulators are becoming less effective against new variants. One variant of SARS-CoV-2 known as B.1.351 that was first reported to be present in South Africa significantly reduces the efficacy of vaccines developed to date. Therapeutic options that work against the B.1.351 variant are therefore urgently needed to counteract reduced vaccine efficacy. We present here the discovery of recombinant alpaca antibodies that neutralise live virus of B.1.351 and other SARS-CoV-2 variants potently. The antibodies described here may be a useful tool for clinicians who are treating patients infected with B.1.351 and other SARS-CoV-2 for which there is currently no known highly effective treatment.

    Program and patient characteristics for the United States Expanded Access Program to COVID-19 MESHD convalescent plasma

    Authors: Jonathon W Senefeld; Patrick W Johnson; Katie L Kunze; Noud van Helmond; Stephen A Klassen; Chad C Wiggins; Katelyn A Bruno; Michael A Golafshar; Molly M Petersen; Matthew R Buras; Allan M Klompas; Matthew A Sexton; Juan C Diaz Soto; Sarah E Baker; John R.A. Shepherd; Nicole C Verdun; Peter Marks; Camille M van Buskirk; Jeffrey L Winters; James R Stubbs; Robert F Rea; Vitaly Herasevich; Emily R Whelan; Andrew J Clayburn; Kathryn F Larson; Juan G Ripoll; Kylie J Andersen; Matthew N.P. Vogt; Joshua J Dennis; Riley J Regimbal; Philippe R Bauer; Janis E Blair; Katherine Wright; Joel T Greenshields; Nigel S Paneth; DeLisa Fairweather; R. Scott Wright; Arturo Casadevall; Rickey E Carter; Michael J Joyner

    doi:10.1101/2021.04.08.21255115 Date: 2021-04-11 Source: medRxiv

    Background The United States (US) Expanded Access Program ( EAP HGNC) to COVID-19 MESHD convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the causative agent of coronavirus disease-2019 ( COVID-19 MESHD). While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents particularly for vulnerable racial and ethnic minority populations who were disproportionately affected by the pandemic. The objective of this study is to report on the demographic, geographic, and chronological access to COVID 19 convalescent plasma in the US via the EAP HGNC. Methods and findings Mayo Clinic served as the central IRB for all participating facilities and any US physician could participate as local physician-principal investigator. Registration occurred through the EAP HGNC central website. Blood banks rapidly developed logistics to provide convalescent plasma to hospitalized patients with COVID-19 MESHD. Demographic and clinical characteristics of all enrolled patients in the EAP HGNC were summarized. Temporal trends in access to COVID-19 MESHD convalescent plasma were investigated by comparing daily and weekly changes in EAP HGNC enrollment in response to changes in infection rate on a state level. Geographical analyses on access to convalescent plasma included assessing EAP HGNC enrollment in all national hospital referral regions as well as assessing enrollment in metropolitan and less populated areas which did not have access to COVID-19 MESHD clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 MESHD were enrolled in the EAP HGNC. A majority of patients were older than 60 years of age (57.8%), male (58.4%), and overweight or obese MESHD (83.8%). There was substantial inclusion of minorities and underserved populations, including 46.4% of patients with a race other than White, and 37.2% of patients were of Hispanic ethnicity. Severe or life-threatening COVID-19 MESHD was present in 61.8% of patients and 18.9% of patients were mechanically ventilated at time of convalescent plasma infusion. Chronologically and geographically, increases in enrollment in the EAP HGNC closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled patients in the EAP HGNC, including both in metropolitan and less populated areas. Conclusions The EAP HGNC successfully provided widespread access to COVID-19 MESHD convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The efficient study design of the EAP HGNC may serve as an example framework for future efforts when broad access to a treatment is needed in response to a dynamic disease affecting demographic groups and areas historically underrepresented in clinical studies.

    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.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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