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Article ; Online: Luteolin Isolated from Juncus acutus L., a Potential Remedy for Human Coronavirus 229E

Asma Hakem / Lowiese Desmarets / Ramla Sahli / Rawen Ben Malek / Charline Camuzet / Nathan François / Gabriel Lefèvre / Jennifer Samaillie / Sophie Moureu / Sevser Sahpaz / Sandrine Belouzard / Riadh Ksouri / Karin Séron / Céline Rivière

Molecules, Vol 28, Iss 4263, p

2023 Volume 4263

Abstract: The COVID-19 pandemic, caused by SARS-CoV-2, addressed the lack of specific antiviral drugs against coronaviruses. In this study, bioguided fractionation performed on both ethyl acetate and aqueous sub-extracts of Juncus acutus stems led to identifying ... ...

Abstract	The COVID-19 pandemic, caused by SARS-CoV-2, addressed the lack of specific antiviral drugs against coronaviruses. In this study, bioguided fractionation performed on both ethyl acetate and aqueous sub-extracts of Juncus acutus stems led to identifying luteolin as a highly active antiviral molecule against human coronavirus HCoV-229E. The apolar sub-extract (CH 2 Cl 2 ) containing phenanthrene derivatives did not show antiviral activity against this coronavirus. Infection tests on Huh-7 cells, expressing or not the cellular protease TMPRSS2, using luciferase reporter virus HCoV-229E-Luc showed that luteolin exhibited a dose-dependent inhibition of infection. Respective IC 50 values of 1.77 µM and 1.95 µM were determined. Under its glycosylated form (luteolin-7- O -glucoside), luteolin was inactive against HCoV-229E. Time of addition assay showed that utmost anti-HCoV-229E activity of luteolin was achieved when added at the post-inoculation step, indicating that luteolin acts as an inhibitor of the replication step of HCoV-229E. Unfortunately, no obvious antiviral activity for luteolin was found against SARS-CoV-2 and MERS-CoV in this study. In conclusion, luteolin isolated from Juncus acutus is a new inhibitor of alphacoronavirus HCoV-229E.
Keywords	HCoV-229E ; SARS-CoV-2 ; MERS-CoV ; Juncus species ; bioguided fractionation ; luteolin ; Organic chemistry ; QD241-441
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Discovery of Anti-Coronavirus Cinnamoyl Triterpenoids Isolated from Hippophae rhamnoides during a Screening of Halophytes from the North Sea and Channel Coasts in Northern France

Malak Al Ibrahim / Zachee Louis Evariste Akissi / Lowiese Desmarets / Gabriel Lefèvre / Jennifer Samaillie / Imelda Raczkiewicz / Sevser Sahpaz / Jean Dubuisson / Sandrine Belouzard / Céline Rivière / Karin Séron

International Journal of Molecular Sciences, Vol 24, Iss 23, p

2023 Volume 16617

Abstract: The limited availability of antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spurred the search for novel antiviral drugs. Here, we investigated the potential antiviral properties of plants adapted to high-salt ... ...

Abstract	The limited availability of antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spurred the search for novel antiviral drugs. Here, we investigated the potential antiviral properties of plants adapted to high-salt environments collected in the north of France. Twenty-five crude methanolic extracts obtained from twenty-two plant species were evaluated for their cytotoxicity and antiviral effectiveness against coronaviruses HCoV-229E and SARS-CoV-2. Then, a bioguided fractionation approach was employed. The most active crude methanolic extracts were partitioned into three different sub-extracts. Notably, the dichloromethane sub-extract of the whole plant Hippophae rhamnoides L. demonstrated the highest antiviral activity against both viruses. Its chemical composition was evaluated by ultra-high performance liquid chromatography (UHPLC) coupled with mass spectrometry (MS) and then it was fractionated by centrifugal partition chromatography (CPC). Six cinnamoyl triterpenoid compounds were isolated from the three most active fractions by preparative high-performance liquid chromatography (HPLC) and identified by high resolution MS (HR-MS) and mono- and bi-dimensional nuclear magnetic resonance (NMR). Specifically, these compounds were identified as 2- O - trans - p -coumaroyl-maslinic acid, 3β-hydroxy-2α- trans - p -coumaryloxy-urs-12-en-28-oic acid, 3β-hydroxy-2α- cis - p -coumaryloxy-urs-12-en-28-oic acid, 3- O - trans -caffeoyl oleanolic acid, a mixture of 3- O - trans -caffeoyl oleanolic acid/3- O - cis -caffeoyl oleanolic acid (70/30), and 3- O - trans - p -coumaroyl oleanolic acid. Infection tests demonstrated a dose-dependent inhibition of these triterpenes against HCoV-229E and SARS-CoV-2. Notably, cinnamoyl oleanolic acids displayed activity against both SARS-CoV-2 and HCoV-229E. Our findings suggest that Hippophae rhamnoides could represent a source of potential antiviral agents against coronaviruses.
Keywords	SARS-CoV-2 ; HCoV-229E ; antiviral agents ; halophytes ; Hippophae rhamnoides ; triterpenoids ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	540
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Correction

Rostyslav Bilyy / Quentin Pagneux / Nathan François / Galyna Bila / Roman Grytsko / Yuri Lebedin / Alexandre Barras / Jean Dubuisson / Sandrine Belouzard / Karin Séron / Rabah Boukherroub / Sabine Szunerits

Pathogens, Vol 12, Iss 12, p

Bilyy et al. Rapid Generation of Coronaviral Immunity Using Recombinant Peptide Modified Nanodiamonds. Pathogens 2021, 10 , 861

2023 Volume 1411

Abstract: In the original publication [.] ...

Abstract	In the original publication [.]
Keywords	n/a ; Medicine ; R
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fluoxetine Can Inhibit SARS-CoV-2 In Vitro

Arthur Dechaumes / Magloire Pandoua Nekoua / Sandrine Belouzard / Famara Sane / Ilka Engelmann / Jean Dubuisson / Enagnon Kazali Alidjinou / Didier Hober

Microorganisms, Vol 9, Iss 2, p

2021 Volume 339

Abstract: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the coronavirus disease pandemic, drastically affecting global health and economy. Though the understanding of the disease has improved, fighting the virus remains ... ...

Abstract	An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the coronavirus disease pandemic, drastically affecting global health and economy. Though the understanding of the disease has improved, fighting the virus remains challenging. One of the strategies is repurposing existing drugs as inhibitors of SARS-CoV-2. Fluoxetine (FLX), a selective serotonin reuptake inhibitor, reportedly inhibits the replication of RNA viruses, especially Coxsackieviruses B (CVB), such as CV-B4 in vitro and in vivo. Therefore, in this study, we investigated the in vitro antiviral activity of FLX against SARS-CoV-2 in a model of acute infection. When 10 μM of FLX was added to SARS-CoV-2-infected Vero E6 cells, the virus-induced cytopathic effect was not observed. In this model, the level of infectious particles in the supernatant was lower than that in controls. The level was below the limit of detection of the assay up to day 3 post-infection when FLX was administered before viral inoculation or simultaneously followed by daily inoculation. In conclusion, FLX can inhibit SARS-CoV-2 in vitro. Further studies are needed to investigate the potential value of FLX to combat SARS-CoV-2 infections, treat SARS-CoV-2-induced diseases, and explain the antiviral mechanism of this molecule to pave way for novel treatment strategies.
Keywords	SARS-CoV-2 ; coronavirus ; fluoxetine ; in vitro ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Rapid Generation of Coronaviral Immunity Using Recombinant Peptide Modified Nanodiamonds

Pathogens, Vol 10, Iss 861, p

2021 Volume 861

Abstract: Vaccination remains one of the most effective tools to prevent infectious diseases. To ensure that the best possible antigenic components are chosen to stimulate a cognitive immune response, boosting antigen presentation using adjuvants is common ... ...

Abstract	Vaccination remains one of the most effective tools to prevent infectious diseases. To ensure that the best possible antigenic components are chosen to stimulate a cognitive immune response, boosting antigen presentation using adjuvants is common practice. Nanodiamond-based adjuvants are proposed here as a rapid and versatile platform for antigen conjugation, utilizing peptides common to different pathogenic strains and making this strategy a good candidate for a “ready-to-use” vaccine. Initiation of an inflammatory reaction with a resulting immune response is based on the ability of living organisms to entrap nanostructures such as nanodiamonds with neutrophil extracellular traps (NETs) formation. In this work, coronavirus peptide homological for MERS-CoV, fusion inhibitor, was conjugated to nanodiamonds and used to induce neutrophilic-driven self-limiting inflammation. The resulting adjuvant was safe and did not induce any tissue damage at the site of injection. Mice immunization resulted in IgG titers of ¼,000 within 28 days. Immunization of rabbits resulted in the formation of a high level of antibodies persistently present for up to 120 days after the first immunization (animal lifespan ~3 years). The peptide used for immunization proved to be reactive with sera of convalescent COVID patients, demonstrating the possibility of developing pancoronaviral vaccine candidates.
Keywords	coronavirus peptide ; diamond nanoparticles ; neutrophil extracellular traps ; Medicine ; R
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Anti-spike, Anti-nucleocapsid and Neutralizing Antibodies in SARS-CoV-2 Inpatients and Asymptomatic Individuals

Etienne Brochot / Baptiste Demey / Antoine Touzé / Sandrine Belouzard / Jean Dubuisson / Jean-Luc Schmit / Gilles Duverlie / Catherine Francois / Sandrine Castelain / Francois Helle

Frontiers in Microbiology, Vol

2020 Volume 11

Abstract: A better understanding of the anti-SARS-CoV-2 immune response is necessary to finely evaluate commercial serological assays but also to predict protection against reinfection and to help the development of vaccines. For this reason, we monitored the anti- ...

Abstract	A better understanding of the anti-SARS-CoV-2 immune response is necessary to finely evaluate commercial serological assays but also to predict protection against reinfection and to help the development of vaccines. For this reason, we monitored the anti-SARS-CoV-2 antibody response in infected patients. In order to assess the time of seroconversion, we used 151 samples from 30 COVID-19 inpatients and monitored the detection kinetics of anti-S1, anti-S2, anti-RBD and anti-N antibodies with in-house ELISAs. We observed that specific antibodies were detectable in all inpatients 2 weeks post-symptom onset and that the detection of the SARS-CoV-2 Nucleocapsid and RBD was more sensitive than the detection of the S1 or S2 subunits. Using retroviral particles pseudotyped with the spike of the SARS-CoV-2, we also monitored the presence of neutralizing antibodies in these samples as well as 25 samples from asymptomatic individuals that were shown SARS-CoV-2 seropositive using commercial serological tests. Neutralizing antibodies reached a plateau 2 weeks post-symptom onset and then declined in the majority of inpatients but they were undetectable in 56% of asymptomatic patients. Our results indicate that the SARS-CoV-2 does not induce a prolonged neutralizing antibody response. They also suggest that induction of neutralizing antibodies is not the only strategy to adopt for the development of a vaccine. Finally, they imply that anti-SARS-CoV-2 neutralizing antibodies should be titrated to optimize convalescent plasma therapy.
Keywords	SARS-CoV-2 ; COVID-19 ; spike ; nucleocapsid ; neutralizing antibodies ; vaccine ; Microbiology ; QR1-502 ; covid19
Subject code	570
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Data_Sheet_1_Anti-spike, Anti-nucleocapsid and Neutralizing Antibodies in SARS-CoV-2 Inpatients and Asymptomatic Individuals.docx

Etienne Brochot / Baptiste Demey / Antoine Touzé / Sandrine Belouzard / Jean Dubuisson / Jean-Luc Schmit / Gilles Duverlie / Catherine Francois / Sandrine Castelain / Francois Helle

2020

Abstract	A better understanding of the anti-SARS-CoV-2 immune response is necessary to finely evaluate commercial serological assays but also to predict protection against reinfection and to help the development of vaccines. For this reason, we monitored the anti-SARS-CoV-2 antibody response in infected patients. In order to assess the time of seroconversion, we used 151 samples from 30 COVID-19 inpatients and monitored the detection kinetics of anti-S1, anti-S2, anti-RBD and anti-N antibodies with in-house ELISAs. We observed that specific antibodies were detectable in all inpatients 2 weeks post-symptom onset and that the detection of the SARS-CoV-2 Nucleocapsid and RBD was more sensitive than the detection of the S1 or S2 subunits. Using retroviral particles pseudotyped with the spike of the SARS-CoV-2, we also monitored the presence of neutralizing antibodies in these samples as well as 25 samples from asymptomatic individuals that were shown SARS-CoV-2 seropositive using commercial serological tests. Neutralizing antibodies reached a plateau 2 weeks post-symptom onset and then declined in the majority of inpatients but they were undetectable in 56% of asymptomatic patients. Our results indicate that the SARS-CoV-2 does not induce a prolonged neutralizing antibody response. They also suggest that induction of neutralizing antibodies is not the only strategy to adopt for the development of a vaccine. Finally, they imply that anti-SARS-CoV-2 neutralizing antibodies should be titrated to optimize convalescent plasma therapy.
Keywords	Microbiology ; Microbial Genetics ; Microbial Ecology ; Mycology ; SARS-CoV-2 ; COVID-19 ; spike ; nucleocapsid ; neutralizing antibodies ; vaccine ; convalescent plasma therapy ; covid19
Subject code	570
Publishing date	2020-10-19T04:17:11Z
Publishing country	uk
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Ross Luu / Silvana Valdebenito / Eliana Scemes / Antonio Cibelli / David C. Spray / Maximiliano Rovegno / Juan Tichauer / Andrea Cottignies-Calamarte / Arielle Rosenberg / Calude Capron / Sandrine Belouzard / Jean Dubuisson / Djillali Annane / Geoffroy Lorin de la Grandmaison / Elisabeth Cramer-Bordé / Morgane Bomsel / Eliseo Eugenin

iScience, Vol 24, Iss 12, Pp 103478- (2021)

2021

Abstract: Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike ... ...

Abstract	Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE2, and IL-1β release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE2, and IL-1β levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy.
Keywords	Cell biology ; Molecular physiology ; Virology ; Science ; Q
Subject code	572
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice.

Sandrine Belouzard / Arnaud Machelart / Valentin Sencio / Thibaut Vausselin / Eik Hoffmann / Nathalie Deboosere / Yves Rouillé / Lowiese Desmarets / Karin Séron / Adeline Danneels / Cyril Robil / Loic Belloy / Camille Moreau / Catherine Piveteau / Alexandre Biela / Alexandre Vandeputte / Séverine Heumel / Lucie Deruyter / Julie Dumont /

Florence Leroux / Ilka Engelmann / Enagnon Kazali Alidjinou / Didier Hober / Priscille Brodin / Terence Beghyn / François Trottein / Benoit Deprez / Jean Dubuisson

PLoS Pathogens, Vol 18, Iss 5, p e

2022 Volume 1010498

Abstract: Drug repurposing has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against ... ...

Abstract	Drug repurposing has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antiviral activity in Vero-81 cells. Among them, clofoctol, an antibacterial drug used for the treatment of bacterial respiratory tract infections, was further investigated due to its favorable safety profile and pharmacokinetic properties. Notably, the peak concentration of clofoctol that can be achieved in human lungs is more than 20 times higher than its IC50 measured against SARS-CoV-2 in human pulmonary cells. This compound inhibits SARS-CoV-2 at a post-entry step. Lastly, therapeutic treatment of human ACE2 receptor transgenic mice decreased viral load, reduced inflammatory gene expression and lowered pulmonary pathology. Altogether, these data strongly support clofoctol as a therapeutic candidate for the treatment of COVID-19 patients.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein

Gary R. Whittaker / Beth N. Licitra / Sandrine Belouzard / Jean K. Millet

Viruses, Vol 4, Iss 6, Pp 1011-

2012 Volume 1033

Abstract: Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus ... ...

Abstract	Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes—A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.
Keywords	coronavirus ; spike ; viral entry ; fusion ; proteolytic activation ; Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
Language	English
Publishing date	2012-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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