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  1. Article ; Online: Anti-human ACE2 antibody neutralizes and inhibits virus production of SARS-CoV-2 variants of concern

    Abigael E. Chaouat / Ilija Brizic / Paola Kucan Brlic / Nofar Atari / Limor Kliker / Or Alfi / Michal Mandelboim / Dana Wolf / Laith Tafish / Inbal Kol / Stipan Jonjic / Ofer Mandelboim

    iScience, Vol 25, Iss 9, Pp 104935- (2022)

    2022  

    Abstract: Summary: The global pandemic caused by SARS-CoV-2 is a major public health problem. Virus entry occurs via binding to ACE2. Five SARS-CoV-2 variants of concern (VOCs) were reported so far, all having immune escape characteristics. Infection with the ... ...

    Abstract Summary: The global pandemic caused by SARS-CoV-2 is a major public health problem. Virus entry occurs via binding to ACE2. Five SARS-CoV-2 variants of concern (VOCs) were reported so far, all having immune escape characteristics. Infection with the current VOC Omicron was noticed in immunized and recovered individuals; therefore, the development of new treatments against VOC infections is urgently needed. Most approved mAbs treatments against SARS-CoV-2 are directed against the spike protein of the original virus and are therefore inefficient against Omicron. Here, we report on the generation of hACE2.16, an anti-ACE2 antibody that recognizes and blocks ACE2-RBD binding without affecting ACE2 enzymatic activity. We demonstrate that hACE2.16 binding to ACE2 does not affect its surface expression and that hACE2.16 blocks infection and virus production of various VOCs including Omicron BA.1 and BA.2. hACE2.16 might, therefore, be an efficient treatment against all VOCs, the current and probably also future ones.
    Keywords Health sciences ; immunology ; immune response ; virology ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Efficacy and safety of metabolic interventions for the treatment of severe COVID-19

    Avner Ehrlich / Konstantinos Ioannidis / Makram Nasar / Ismaeel Abu Alkian / Yuval Daskal / Nofar Atari / Limor Kliker / Nir Rainy / Matan Hofree / Sigal Shafran Tikva / Inbal Houri / Arrigo Cicero / Chiara Pavanello / Cesare R Sirtori / Jordana B Cohen / Julio A Chirinos / Lisa Deutsch / Merav Cohen / Amichai Gottlieb /
    Adina Bar-Chaim / Oren Shibolet / Michal Mandelboim / Shlomo L Maayan / Yaakov Nahmias

    eLife, Vol

    in vitro, observational, and non-randomized open-label interventional study

    2023  Volume 12

    Abstract: Background: Viral infection is associated with a significant rewire of the host metabolic pathways, presenting attractive metabolic targets for intervention. Methods: We chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in ... ...

    Abstract Background: Viral infection is associated with a significant rewire of the host metabolic pathways, presenting attractive metabolic targets for intervention. Methods: We chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples and perform in vitro metabolism-focused drug screen on primary lung epithelial cells infected with different strains of the virus. We perform observational analysis of Israeli patients hospitalized due to COVID-19 and comparative epidemiological analysis from cohorts in Italy and the Veteran’s Health Administration in the United States. In addition, we perform a prospective non-randomized interventional open-label study in which 15 patients hospitalized with severe COVID-19 were given 145 mg/day of nanocrystallized fenofibrate added to the standard of care. Results: SARS-CoV-2 infection produced transcriptional changes associated with increased glycolysis and lipid accumulation. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication through a PPARα-dependent mechanism in both alpha and delta variants. Analysis of 3233 Israeli patients hospitalized due to COVID-19 supported in vitro findings. Patients taking fibrates showed significantly lower markers of immunoinflammation and faster recovery. Additional corroboration was received by comparative epidemiological analysis from cohorts in Europe and the United States. A subsequent prospective non-randomized interventional open-label study was carried out on 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to patients admitted during the same period. Conclusions: Taken together, our data suggest that pharmacological modulation of PPARα should be strongly considered as a potential ...
    Keywords translational research ; COVID-19 ; metabolic regulation ; drug repurposing ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: The Rise and Fall of a Local SARS-CoV-2 Variant with the Spike Protein Mutation L452R

    Orna Mor / Michal Mandelboim / Shay Fleishon / Efrat Bucris / Dana Bar-Ilan / Michal Linial / Ital Nemet / Limor Kliker / Yaniv Lustig / Israel National Consortium for SARS-CoV-2 Sequencing / Ella S. Mendelson / Neta S. Zuckerman

    Vaccines, Vol 9, Iss 937, p

    2021  Volume 937

    Abstract: Emerging SARS-CoV-2 variants may threaten global vaccination efforts and the awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R ... ...

    Abstract Emerging SARS-CoV-2 variants may threaten global vaccination efforts and the awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.
    Keywords SARS-CoV-2 ; variant ; mutation ; sequencing ; neutralization ; Medicine ; R
    Subject code 572
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2

    Ma’ayan Israeli / Yaara Finkel / Yfat Yahalom-Ronen / Nir Paran / Theodor Chitlaru / Ofir Israeli / Inbar Cohen-Gihon / Moshe Aftalion / Reut Falach / Shahar Rotem / Uri Elia / Ital Nemet / Limor Kliker / Michal Mandelboim / Adi Beth-Din / Tomer Israely / Ofer Cohen / Noam Stern-Ginossar / Adi Bercovich-Kinori

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 16

    Abstract: Here, Israeli and Finkel et al. perform genome-wide CRISPR knockout screens to identify host factors required for the infection with SARS-CoV-2 and two additionally variants of concern, Alpha and Beta, unveiling shared and differential host pathways ... ...

    Abstract Here, Israeli and Finkel et al. perform genome-wide CRISPR knockout screens to identify host factors required for the infection with SARS-CoV-2 and two additionally variants of concern, Alpha and Beta, unveiling shared and differential host pathways required by the variants, and demonstrate GATA6 is critical for SARS-CoV-2 viral entry through modulation of ACE2 expression.
    Keywords Science ; Q
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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