Article
Biology
Lenka Stejskal, Mphatso D. Kalemera, Charlotte B. Lewis, Machaela Palor, Lucas Walker, Tina Daviter, William D. Lees, David S. Moss, Myrto Kremyda-Vlachou, Zisis Kozlakidis, Giulia Gallo, Dalan Bailey, William Rosenberg, Christopher J. R. Illingworth, Adrian J. Shepherd, Joe Grove
Summary: This study reveals that the hypervariable region-1 (HVR-1) of the fusion proteins E1E2 in Hepatitis C Virus (HCV) has an autoinhibitory function that controls the activity of the proteins. The mechanism is turned off by host receptor interactions, allowing virus entry. Mutations or deletion of HVR-1 results in enhanced virus entry but increased sensitivity to neutralising antibodies.
Article
Virology
Kamilla Toon, Mphatso D. Kalemera, Machaela Palor, Nicola J. Rose, Yasuhiro Takeuchi, Joe Grove, Giada Mattiuzzo
Summary: Due to increased and broadened screening efforts, the number of viral species in the Hepacivirus genus has rapidly expanded. Genetic features of hepaciviruses suggest they have adapted and evolved to hijack host proteins for efficient liver propagation. A study on GB virus B (GBV-B) found that claudin-1 is an essential entry factor, shared with hepatitis C virus (HCV), but with distinct mechanisms of entry. Understanding the molecular mechanisms of hepacivirus entry can inform the design of new vaccines and treatments targeting the first stage of HCV infection.
JOURNAL OF VIROLOGY
(2023)
Review
Microbiology
Emmanuelle V. LeBlanc, Youjin Kim, Chantelle J. Capicciotti, Che C. Colpitts
Summary: This review provides an overview of the roles of viral and cellular glycans in HCV infection and highlights advances in the development of entry inhibitors and vaccines to effectively prevent HCV infection.
Article
Biochemistry & Molecular Biology
Hyung Chul Ryu, Marc Windisch, Jee Woong Lim, Inhee Choi, Eun Kyu Lee, Hye Hyun Yoo, Tae Kon Kim
Summary: Novel small-molecule inhibitors of hepatitis C virus (HCV) were synthesized and screened, with J2H-1701 identified as the optimized lead compound for HCV entry inhibition based on its potent antiviral activity and safety profile. This compound showed effective multi-genotypic antiviral activity and potential interaction with the HCV E2 glycoprotein, suggesting it as a candidate drug for HCV entry inhibition.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Review
Microbiology
Anshuman Das, Efrain E. Rivera-Serrano, Xin Yin, Christopher M. Walker, Zongdi Feng, Stanley M. Lemon
Summary: In this Review, the authors discuss quasi-enveloped virions, their entry and release from human host cells, and their impact on host immunity and pathogenesis. They focus on hepatitis A and E viruses, which were previously considered non-enveloped but are now known to be released as quasi-enveloped virions cloaked in host membranes. Despite lacking virally encoded proteins on their surface, these virions efficiently enter cells and replicate. The authors also describe the mechanisms by which specific peptide sequences in the capsids of these virions mediate their release from hepatocytes and the current understanding of their cell entry mechanism.
NATURE REVIEWS MICROBIOLOGY
(2023)
Review
Gastroenterology & Hepatology
Hui-Chun Li, Chee-Hing Yang, Shih-Yen Lo
Summary: HCV, an obligatory intracellular pathogen, relies heavily on host cells for successful propagation. Its lifecycle includes stages such as viral entry, protein translation, RNA replication, viral assembly, and release, with hundreds of cellular factors identified over three decades of research. These factors, some of which are targeted for anti-HCV therapies, provide valuable insight into HCV replication strategies.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Review
Virology
Chui-Wa So, Glenn Randall
Summary: Hepatocytes, the main target of HCV, require extensive trafficking in polarized cells for infection. Researchers are utilizing three-dimensional cell culture models resembling in vivo hepatocytes to study HCV infection.
Article
Microbiology
Ahmed K. Oraby, Cassandra L. Gardner, Robert F. Needle, Hassan M. Kofahi, Kylie R. Everard, Nathan G. A. Taylor, Suzette G. Rutihinda, Jacqueline P. Barry, Kensuke Hirasawa, Paris E. Georghiou, Rodney S. Russell
Summary: The novel small-molecule compound AO13 demonstrated a consistent but low-level antiviral effect against HCV, potentially acting on a late stage in the viral life cycle. This compound could serve as a lead compound for future drug development against other important viruses.
MICROBIOLOGY SPECTRUM
(2021)
Article
Gastroenterology & Hepatology
Penglei Jiang, Hongyu Jia, Xinyue Qian, Tian Tang, Yingli Han, Zhaoru Zhang, Lingli Jiang, Zebin Yu, Lin Zheng, Guodong Yu, Huan Cai, Shanyan Zhang, Xiaoli Zhang, Jueqing Gu, Chanyuan Ye, Lisha Yang, Yingfeng Lu, Heng Liu, Xiaoqing Lu, Ciliang Jin, Yue Ren, Miaomiao Lu, Lingling Xu, Jiong Yu, Xi Jin, Yida Yang, Pengxu Qian
Summary: This study used single-cell RNA sequencing to investigate the transcriptomic landscape of peripheral immune cells in CHB patients before and after PegIFN-alpha therapy. The study identified specific cell subsets associated with CHB and found that PegIFN-alpha treatment could decrease hyperactivated monocytes, increase long-lived naive/memory T cells, and enhance effector T cell cytotoxicity. Furthermore, the treatment altered the transcriptional profiles of immune cells and enhanced innate antiviral response.
Article
Biochemistry & Molecular Biology
Keiji Ueda, Yadarat Suwanmanee
Summary: The precise mechanism of HBV entry into cells is still largely unknown. However, researchers have identified ATP5B as an essential factor for HBV entry, which is believed to bind with myristoylated preS1 2-47. Knockdown of ATP5B in NTCP-expressing HepG2 cells reduced HBV infectivity, indicating that ATP5B is involved in the HBV entry process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Gastroenterology & Hepatology
Alessandra Mangia, Rosa Cotugno, Giovanna Cocomazzi, Maria Maddalena Squillante, Valeria Piazzolla
Summary: The World Health Organization's goal of eliminating Hepatitis C virus (HCV) by 2030 using direct-acting antiviral treatments has become less attainable post the 2020 pandemic of coronavirus disease 2019. Therefore, a more realistic approach of micro-elimination in population segments where targeted strategies of prevention and treatment are easily attained has been promoted in Europe. Active involvement of stakeholders and community participation are essential components for the success of a micro-elimination project tailored at the geographical level according to HCV epidemiology and individual country's income.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Medicine, General & Internal
Heiner Wedemeyer, Soo Aleman, Maurizia Rossana Brunetto, Antje Blank, Pietro Andreone, Pavel Bogomolov, Vladimir Chulanov, Nina Mamonova, Natalia Geyvandova, Viacheslav Morozov, Olga Sagalova, Tatyana Stepanova, Annemarie Berger, Dmitry Manuilov, Vithika Suri, Qi An, Ben Da, John Flaherty, Anu Osinusi, Yang Liu, Uta Merle, Julian Schulzezur Wiesch, Stefan Zeuzem, Sandra Ciesek, Markus Cornberg, Pietro Lampertico
Summary: In this study, it was found that bulevirtide is effective in inhibiting the entry of hepatitis D virus and reducing the progression of liver disease in patients with chronic hepatitis B. The recommended dosage of bulevirtide is 2 mg or 10 mg per day.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Medicine, General & Internal
Heiner Wedemeyer, Soo Aleman, Maurizia Rossana Brunetto, Antje Blank, Pietro Andreone, Pavel Bogomolov, Vladimir Chulanov, Nina Mamonova, Natalia Geyvandova, Viacheslav Morozov, Olga Sagalova, Tatyana Stepanova, Annemarie Berger, Dmitry Manuilov, Vithika Suri, Qi An, Ben Da, John Flaherty, Anu Osinusi, Yang Liu, Uta Merle, Julian Schulze zur Wiesch, Stefan Zeuzem, Sandra Ciesek, Markus Cornberg, Pietro Lampertico
Summary: Bulevirtide treatment reduces HDV RNA and ALT levels in patients with chronic hepatitis D, with a dose-dependent effect.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Biophysics
Ru Cheng, Fu Zhu, Min Huang, Qiang Zhang, Hui Hong Yan, Xiao Hui Zhao, Fu Kang Luo, Chun Mei Li, Hui Liu, Gao Lin Liang, Cheng Zhi Huang, Jian Wang
Summary: In this study, a new biosensor named hepatitis virus indicator was developed for the simultaneous detection of HBV and HCV. The biosensor utilized Exo III assisted signal amplification strategy and particle counting technology with a dark-field microscopy, enabling sensitive and selective detection.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Microbiology
Yingying Li, Guangxiang Luo
Summary: HBV infection is a major global health issue, with current treatments being limited. Recent research has shown that LDLR plays a crucial role in HBV infection, suggesting potential new avenues for HBV therapy. Further studies are needed to explore the involvement of other LDLR family members in HBV infection.
Article
Microbiology
Thomas Meunier, Lowiese Desmarets, Simon Bordage, Moussa Bamba, Kevin Hervouet, Yves Rouille, Nathan Francois, Marion Decossas, Valentin Sencio, Francois Trottein, Fezan Honora Tra Bi, Olivier Lambert, Jean Dubuisson, Sandrine Belouzard, Sevser Sahpaz, Karin Seron
Summary: The study identified pheophorbide a (Pba) as a highly active antiviral molecule against SARS-CoV-2, MERS-CoV, and other enveloped viruses. Pba inhibits virus entry by directly targeting the viral particle and stiffening the viral membrane. The antiviral activity of Pba is dependent on light exposure. This natural antiviral compound holds potential for COVID-19 therapy and disinfection of SARS-CoV-2-contaminated surfaces.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Virology
Eloine Bestion, Keivan Zandi, Sandrine Belouzard, Julien Andreani, Hubert Lepidi, Marie Novello, Clara Rouquairol, Jean-Pierre Baudoin, Madani Rachid, Bernard La Scola, Jean-Louis Mege, Jean Dubuisson, Raymond F. Schinazi, Soraya Mezouar, Philippe Halfon
Summary: Since December 2019, the rapid spread of SARS-CoV-2 worldwide has caused over 280 million confirmed cases and 5 million deaths. Researchers have found that coronaviruses can hijack the autophagic process to facilitate viral replication. GNS561, a late-stage autophagy inhibitor, has shown antiviral activity against SARS-CoV-2 with a range of 6-40 nM, making it the most powerful molecule investigated for SARS-CoV-2 infection. GNS561 disrupts the autophagy mechanism and reduces SARS-CoV-2 virions in a mouse model.
Article
Pharmacology & Pharmacy
Moussa Bamba, Simon Bordage, Marie-Emmanuelle Sahuc, Sophie Moureu, Jennifer Samaillie, Vincent Roumy, Peggy Vauchel, Krasimir Dimitrov, Yves Rouille, Jean Dubuisson, Fezan Honora Tra Bi, Karin Seron, Sevser Sahpaz
Summary: The Carapa procera DC. and Pericopsis laxiflora (Benth.ex Baker) Meeuwen species from Cote d'Ivoire were found to have high antiviral activity against HCV, with low toxicity for hepatic cells. The crude extracts from these plants were rich in polyphenols, including active tannins. Removing the tannins from the extracts resulted in a loss of anti-HCV activity. Using a hydro-ethanolic solvent instead of methanol produced tannin-rich extracts with similar antiviral activity.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Gastroenterology & Hepatology
Valentin Sencio, Arnaud Machelart, Cyril Robil, Nicolas Benech, Eik Hoffmann, Chloe Galbert, Lucie Deryuter, Severine Heumel, Aline Hantute-Ghesquier, Anne Flourens, Priscille Brodin, Fabrice Infanti, Virgile Richard, Jean Dubuisson, Corinne Grangette, Thierry Sulpice, Isabelle Wolowczuk, Florence Pinet, Vincent Prevot, Sandrine Belouzard, Francois Briand, Martine Duterque-Coquillaud, Harry Sokol, Francois Trottein
Summary: Mounting evidence suggests that the gut plays a critical role during respiratory viral infections. Using a hamster model, this study found that SARS-CoV-2 infection led to intestinal inflammation, altered intestinal barrier property, liver inflammation, and disrupted lipid metabolism. The changes were accompanied by alterations in the gut microbiota composition, characterized by an increase in harmful bacterial taxa and a decrease in bacteria that produce SCFAs. These alterations in the gut microbiota were correlated with disease severity in hamsters.
Article
Microbiology
Sandrine Belouzard, Arnaud Machelart, Valentin Sencio, Thibaut Vausselin, Eik Hoffmann, Nathalie Deboosere, Yves Rouille, Lowiese Desmarets, Karin Seron, Adeline Danneels, Cyril Robil, Loic Belloy, Camille Moreau, Catherine Piveteau, Alexandre Biela, Alexandre Vandeputte, Severine Heumel, Lucie Deruyter, Julie Dumont, Florence Leroux, Ilka Engelmann, Enagnon Kazali Alidjinou, Didier Hober, Priscille Brodin, Terence Beghyn, Francois Trottein, Benoit Deprez, Jean Dubuisson
Summary: In this study, the researchers screened a library of drug compounds to identify potential antivirals against SARS-CoV-2. They discovered that clofoctol, an antibacterial drug used for respiratory tract infections, exhibited significant antiviral activity and had favorable safety and pharmacokinetic properties. In vivo experiments showed that clofoctol reduced inflammatory gene expression and pulmonary pathology. These findings suggest that clofoctol could be a promising therapeutic candidate for the treatment of COVID-19 patients.
Article
Microbiology
Karoline Metzger, Cyrine Bentaleb, Kevin Hervouet, Virginie Alexandre, Claire Montpellier, Jean-Michel Saliou, Martin Ferrie, Charline Camuzet, Yves Rouille, Cecile Lecoeur, Jean Dubuisson, Laurence Cocquerel, Cecile-Marie Aliouat-Denis
Summary: This study aims to elucidate the replication step of Hepatitis E virus (HEV) and identify the replication location within host cells. By inserting epitope tags and conducting protein analysis, we discovered the significant role of ORF1 polyprotein in the cell nucleus and perinuclear substructures and identified potential replication factories for HEV.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aiwei Zhu, Fernando Real, Claude Capron, Arielle R. Rosenberg, Aymeric Silvin, Garett Dunsmore, Jaja Zhu, Andrea Cottoignies-Callamarte, Jean-Marc Masse, Pierre Moine, Simon Bessis, Mathieu Godement, Guillaume Geri, Jean-Daniel Chiche, Silvana Valdebenito, Sandrine Belouzard, Jean Dubuisson, Geoffroy Lorin de la Grandmaison, Sylvie Chevret, Florent Ginhoux, Eliseo A. Eugenin, Djillali Annane, Elisabeth Cramer Borde, Morgane Bomsel
Summary: This study found that circulating platelets containing SARS-CoV-2 are closely associated with fatal outcomes in severe COVID-19 patients. The infected platelets may originate from bone marrow and lung megakaryocytes, which are also found infected in COVID-19 autopsies. The interaction between infected platelets and lung macrophages may have an impact on the pathogenesis of COVID-19.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Virology
Muriel Lavie, Jean Dubuisson, Sandrine Belouzard
Summary: SARS-CoV-2 spike protein is essential for virus entry into host cells and is a target for therapeutics development. The processing and cleavage of spike protein at different sites are crucial for its entry functions, and these processes are influenced by the host cell background. Our findings highlight the heterogeneity in spike sequence requirements for entry functions in different host cells, which aligns with the adaptability of SARS-CoV-2 virus.
JOURNAL OF VIROLOGY
(2022)
Article
Genetics & Heredity
Antoine Rebendenne, Priyanka Roy, Boris Bonaventure, Ana Luiza Chaves Valadao, Lowiese Desmarets, Mary Arnaud-Arnould, Yves Rouille, Marine Tauziet, Donatella Giovannini, Jawida Touhami, Yenarae Lee, Peter DeWeirdt, Mudra Hegde, Serge Urbach, Khadija El Koulali, Francisco Garcia de Gracia, Joe McKellar, Jean Dubuisson, Melanie Wencker, Sandrine Belouzard, Olivier Moncorge, John G. Doench, Caroline Goujon
Summary: Genome-wide CRISPR knockout and activation screens in Calu-3 lung cells and Caco-2 colorectal cells identify host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs.
Article
Microbiology
Stephanie Thebault, Nathalie Lejal, Alexis Dogliani, Amelie Donchet, Agathe Urvoas, Marie Valerio-Lepiniec, Muriel Lavie, Cecile Baronti, Franck Touret, Bruno Da Costa, Clara Bourgon, Audrey Fraysse, Audrey Saint-Albin-Deliot, Jessica Morel, Bernard Klonjkowski, Xavier de Lamballerie, Jean Dubuisson, Alain Roussel, Philippe Minard, Sophie Le Poder, Nicolas Meunier, Bernard Delmas
Summary: The study identified candidates that can interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, inhibiting virus entry into cells and neutralizing various SARS-CoV-2 variants. These findings provide a new strategy for developing therapeutics against SARS-CoV-2.
Article
Oncology
Olga A. Smirnova, Olga N. Ivanova, Irina T. Fedyakina, Gaukhar M. Yusubalieva, Vladimir P. Baklaushev, Dmitry V. Yanvarev, Olga I. Kechko, Vladimir A. Mitkevich, Pavel O. Vorobyev, Vyacheslav S. Fedorov, Birke Bartosch, Vladimir T. Valuev-Elliston, Anastasiya L. Lipatova, Alexander V. Ivanov
Summary: This study found that the novel coronavirus can infect liver cancer cells and certain types of brain tumor cells, but not normal liver cells. Additionally, the study found that viral infection may lead to a decrease in the differentiation level of liver cells. Overall, these results suggest that liver dysfunction during COVID-19 is not caused by SARS-CoV-2 infection, and tumors may potentially serve as reservoirs for the virus during infection.
Article
Chemistry, Medicinal
Lucile Brier, Haitham Hassan, Xavier Hanoulle, Valerie Landry, Danai Moschidi, Lowiese Desmarets, Yves Rouille, Julie Dumont, Adrien Herledan, Sandrine Warenghem, Catherine Piveteau, Paul Carr, Sarah Ikherbane, Francois-Xavier Cantrelle, Elian Dupre, Jean Dubuisson, Sandrine Belouzard, Florence Leroux, Benoit Deprez, Julie Charton
Summary: Since the end of 2019, the global outbreak of the coronavirus SARS-CoV-2 has caused a significant increase in infections and deaths worldwide. Researchers have identified two proteases, 3CLpro and papain-like protease, encoded by the virus that play a crucial role in the virus lifecycle. Targeting the 3CLpro, which is highly conserved within this viral family, a screening of over 89,000 small molecules led to the discovery of a potent inhibitor of the SARS-CoV-2 3CLpro. The mechanism of inhibition, interaction with the protease, specificity against host proteases, and promising antiviral properties in cells are reported.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Olga N. Ivanova, George S. Krasnov, Anastasiya V. Snezhkina, Anna V. Kudryavtseva, Vyacheslav S. Fedorov, Natalia F. Zakirova, Michail V. Golikov, Sergey N. Kochetkov, Birke Bartosch, Vladimir T. Valuev-Elliston, Alexander V. Ivanov
Summary: ROS play a major role in cell regulation, and their increase is associated with the development of various pathologies. This study analyzed gene expression of redox systems and related metabolic processes in hepatoma cells and liver progenitor cell lines, shedding light on the redox biology of viral hepatitis and the influence of laboratory models.
Article
Biochemistry & Molecular Biology
Olga A. Smirnova, Olga N. Ivanova, Furkat Mukhtarov, Vladimir T. Valuev-Elliston, Artemy P. Fedulov, Petr M. Rubtsov, Natalia F. Zakirova, Sergey N. Kochetkov, Birke Bartosch, Alexander V. Ivanov
Summary: Hepatitis delta virus (HDV) enhances oxidative and ER stress induced by hepatitis B virus (HBV), aggravating HBV-associated pathologies.
Article
Biochemistry & Molecular Biology
Lowiese Desmarets, Adeline Danneels, Julien Burlaud-Gaillard, Emmanuelle Blanchard, Jean Dubuisson, Sandrine Belouzard
Summary: The membrane protein of Middle East respiratory syndrome coronavirus (MERS-CoV) plays a crucial role in the virus assembly process. Proper intracellular trafficking and subcellular localization of the M protein are essential for virus formation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)