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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314838

ABSTRACT

A new phase of the COVID-19 pandemic has started as SARS-CoV-2 variants are emerging globally, raising concerns for increased transmissibility. Early 2021 the B.1.1.7 (or Alpha) variant, became the dominant variant globally and epidemiological data suggests this variant spreads faster than its ancestors. However, this does not prove that a variant is intrinsically phenotypically different, let alone more transmissible or fit. Therefore, rapid phenotyping of SARS-CoV-2 variants of concern is urgently needed. We found that airway, intestinal and alveolar organoids infected with the B.1.1.7 variant produced higher levels of infectious virus late in infection compared to its 614G-containing ancestor. The B.1.1.7 variant also had a clear fitness advantage in human airway organoids. In alveolar organoids, the B.1.1.7 variant induced lower levels of innate immunity. These findings suggest that the B.1.1.7 variant is phenotypically different from its ancestor and may explain why this clade has spread rapidly across the globe.Funding Information: This work was supported by Netherlands Organization for Health Research and Development (10150062010008;B.L.H.), PPP allowance (LSHM19136;B.L.H.). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 874735. Declaration of Interests: H.C. is inventor on patents held by the Royal Netherlands Academy of Arts and Sciences that cover organoid technology. H.C.’s full disclosure is given at https://www.uu.nl/staff/JCClevers. All other authors have nothing to declare. Ethics Approval Statement: The Medical Ethical Committee of the Erasmus MC Rotterdam granted permission for this study (METC 2012-512). The study was approved by the UMC Utrecht (Utrecht, The Netherlands) ethical committee and was in accordance with the Declaration of Helsinki and according to Dutch law. This study is compliant with all relevant ethical regulations regarding research involving human participants.

2.
Ain Shams Engineering Journal ; 2021.
Article in English | ScienceDirect | ID: covidwho-1499628

ABSTRACT

Digital education in schools through artificial intelligence, big data and other technologies is conducive to improving teaching efficiency and promoting teaching progress. Unfortunately, many schools lack a sense of social responsibility when applying digital education.Students are online more than ever before. There are the potential for increased exposure to risks such as exposure to harmful content, cyberbullying, age-inappropriate advertising and data misuse, which affect students’ well-being and undermine their right to privacy.Schools should bear the overall social moral level of social responsibility. This paper focuses on the social responsibility of schools under the new crown epidemic and holds that implanting social responsibility into the value system of the current digital education reform,which can promote the sustainable development of education. This is also a relatively neglected problem in the practice of educational reform. European standard: ISO26000 is adopted as a CEN-standard. 21 October 2020 the stakeholder consultation process in the European Committee for Standardization (CEN) decided that ISO 26000 is approved as a CEN-standard. For businesses and organizations committed to operating in a socially responsible way, there’s ISO 26000. It provides guidance to those who recognize that respect for society and environment is a critical success factor. This paper highlights the school how to take social responsibility by using ISO 26000.Based on the seven subjects of ISO 26000, this paper constructs the social responsibility of digital education frame, focuses on analyzing the main content and core issues of social responsibility of digital education, puts forward some improved strategies and suggestions for the more prominent problems at this stage through the examination and reflection of reality.

3.
Nat Commun ; 12(1): 5498, 2021 09 17.
Article in English | MEDLINE | ID: covidwho-1428814

ABSTRACT

Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Genetic screens are often performed in transformed cell lines that poorly represent viral target cells in vivo, leading to discoveries that may not be translated to the clinic. Intestinal organoids are increasingly used to model human disease and are amenable to genetic engineering. To discern which host factors are reliable anti-coronavirus therapeutic targets, we generate mutant clonal IOs for 19 host genes previously implicated in coronavirus biology. We verify ACE2 and DPP4 as entry receptors for SARS-CoV/SARS-CoV-2 and MERS-CoV respectively. SARS-CoV-2 replication in IOs does not require the endosomal Cathepsin B/L proteases, but specifically depends on the cell surface protease TMPRSS2. Other TMPRSS family members were not essential. The newly emerging coronavirus variant B.1.1.7, as well as SARS-CoV and MERS-CoV similarly depended on TMPRSS2. These findings underscore the relevance of non-transformed human models for coronavirus research, identify TMPRSS2 as an attractive pan-coronavirus therapeutic target, and demonstrate that an organoid knockout biobank is a valuable tool to investigate the biology of current and future emerging coronaviruses.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Biological Specimen Banks , CRISPR-Cas Systems , Coronavirus , Dipeptidyl Peptidase 4/genetics , Organoids/metabolism , Serine Endopeptidases/genetics , COVID-19 , Cell Line , Humans , Middle East Respiratory Syndrome Coronavirus , SARS-CoV-2 , Transcriptome , Virus Replication
4.
Biochimie ; 179: 229-236, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1326922

ABSTRACT

The ongoing pandemic of COVID-19 (Coronavirus Disease-2019), a respiratory disease caused by the novel coronavirus strain, SARS-CoV-2, has affected more than 42 million people already, with more than one million deaths worldwide (as of October 25, 2020). We are in urgent need of therapeutic interventions that target the host-virus interface, which requires a molecular understanding of the SARS-CoV-2 life-cycle. Like other positive-sense RNA viruses, coronaviruses remodel intracellular membranes to form specialized viral replication compartments, including double-membrane vesicles (DMVs), where viral RNA genome replication takes place. Here we review the current knowledge of the structure, lipid composition, function, and biogenesis of coronavirus-induced DMVs, highlighting the druggable viral and cellular factors that are involved in the formation and function of DMVs.


Subject(s)
Cell Membrane/metabolism , Coronavirus/physiology , Host Microbial Interactions , Virus Replication , Cell Membrane/virology , Humans , Molecular Targeted Therapy
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