Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1295550 | ENA |
REPOSITORIES: ENA
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Project description:The COVID-19 pandemic has claimed the lives of more than one million people worldwide. The causative agent, SARS-CoV-2, is a member of the Coronaviridae family, which are viruses that cause respiratory infections of varying severity. The cellular host factors and pathways co-opted by SARS- CoV-2 and other coronaviruses in the execution of their life cycles remain ill-defined. To develop an extensive compendium of host factors required for infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E), we performed parallel genome-scale CRISPR knockout screens. These screens uncovered multiple host factors and pathways with pan- coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, SREBP signaling, BMP signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VTT-domain containing protein TMEM41B for infection by SARS-CoV-2 and three seasonal coronaviruses. This human Coronaviridae host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus spillover events.
2020-11-24 | GSE162038 | GEO
Project description:We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal (HCoV-NL63, -229E, -OC43 and -HKU1) and epidemic coronaviruses (SARS-CoV, hCoV-MERS) at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed IgG antibody reactivity to nucleocapsid and spike antigens using protein microarray. A cutoff was set at the average plus 3 times the SD of 20 nonreactive cultures with a minimum MFI of 1000.
2022-09-30 | E-MTAB-12161 | biostudies-arrayexpress
Project description:Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against SARS-CoV-2. Previous studies have shown divergent results regarding protective or damaging immunity induced by prior exposure to sCoVs. It is still unknown whether pre-existing humoral immunity may play a role in the vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera in healthy volunteers before and after immunization with inactivated SARS-CoV-2 vaccines, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level before vaccine immunization, as well as the relationship between pre-existing sCoVs immunity and vaccine-induced neutralization.
2021-10-13 | E-MTAB-11084 | biostudies-arrayexpress
Project description:Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against SARS-CoV-2. Previous studies have shown divergent results regarding protective or damaging immunity induced by prior exposure to sCoVs. It is still unknown whether pre-existing humoral immunity may play a role in the vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera in healthy volunteers before and after immunization with inactivated SARS-CoV-2 vaccines, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level before vaccine immunization, as well as the relationship between pre-existing sCoVs immunity and vaccine-induced neutralization.
2021-10-29 | E-MTAB-11117 | biostudies-arrayexpress
Project description:All coronaviruses known to have recently emerged as human pathogens probably originated in bats1. Here we use a single experimental platform based on immunodeficient mice implanted with human lung tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801?an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials?markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19.
2020-09-23 | GSE155286 | GEO
Project description:Convalescent sera of RT-PCR SARS-CoV-2 confirmed hospitalised patients were tested on the protein array to profile IgG, IgM, and IgA antibody levels against human coronaviruses.
2022-03-08 | E-MTAB-11523 | biostudies-arrayexpress
Project description:Seasonal coronaviruses, including HCoV-229E, -NL63, -OC43, and -HKU1, are prevalent worldwide, predominantly causing mild, self-limiting upper respiratory (re-)infections in adults, often presenting as the common cold. However, in individuals with compromised immune systems, these viruses may lead to more severe illness and even fatalities. Recently, there has been a renewed interest in studying HCoVs due to their amenability to handling in reduced biosafety containment, offering valuable alternatives to SARS-CoV-2 for preclinical screening and the development of antiviral treatments. Despite their significance, research on HCoVs has been hindered by limited host-genomic data. To address this, we performed RNA-sequencing on 3D air-liquid interface human nasal airway epithelial cells (hNECs) infected with the alphacoronavirus HCoV-229E and the betacoronavirus HCoV-OC43. These hNECs were derived from pooled adult donors and exhibited pseudostratified mucociliated differentiation, faithfully replicating the complexities of normal airway biology. Our study aimed to identify specific immune signatures associated with HCoV infections in a physiologically relevant model. By elucidating the host responses induced by different seasonal coronaviruses, we can gain valuable insights into their pathogenesis and interactions with the respiratory epithelium. This knowledge may pave the way for the development of targeted therapeutics and prophylactics to combat HCoV infections effectively.
2025-07-01 | GSE238079 | GEO
Project description:Furin cleavage in European SARS-related bat coronaviruses
| PRJEB51900 | ENA
Project description:The ongoing SARS-CoV-2 pandemic has devastated the global economy and claimed more than one million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designed a focused high-coverage CRISPR-Cas9 library targeting 332 members of a recently published SARS-CoV-2 protein interactome. We leveraged the compact nature of this library to systematically screen SARS-CoV-2 at two physiologically relevant temperatures (33 ºC and 37 ºC) along with three related coronaviruses (HCoV-229E, HCoV-NL63, and HCoV-OC43), allowing us to probe this interactome at a much higher resolution relative to genome scale studies. This approach yielded several new insights, including unexpected virus-specific differences in Rab GTPase requirements and GPI anchor biosynthesis, as well as identification of multiple pan-coronavirus factors involved in cholesterol homeostasis. This coronavirus essentiality catalog could inform ongoing drug development efforts aimed at intercepting and treating COVID-19, and help prepare for future coronavirus outbreaks.
2020-11-24 | GSE162039 | GEO
Project description:Seasonal coronaviruses, similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), only cause severe respiratory symptoms in a small fraction of infected individuals. However, the host factors that determine the variable responses to coronavirus infection remain unclear. Here, we use seasonal human coronavirus OC43 (HCoV-OC43) infection as an asymptomatic model that triggers both innate and adaptive immune responses in mice. Interestingly, innate sensing pathways as well as adaptive immune cells are not essential in protection against HCoV-OC43. Instead, alveolar macrophage (AMΦ) deficiency in mice results in COVID-19-like severe pneumonia post HCoV-OC43 infection, with abundant neutrophil infiltration, neutrophil extracellular trap (NET) release, and exaggerated pro-inflammatory cytokine production. Mechanistically, AMΦ efficiently phagocytose HCoV-OC43, effectively blocking virus spread, whereas, in their absence, HCoV-OC43 triggers Toll-like receptor (TLR)-dependent chemokine production to cause pneumonia. These findings reveal the central role of AMΦ in defending against seasonal HCoV-OC43 with clinical implications for human immunopathology associated with coronavirus infection.
2025-10-21 | GSE289734 | GEO