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)
Article
Gastroenterology & Hepatology
Qingyan Wu, Mirco Glitscher, Susanne Tonnemacher, Anja Schollmeier, Jan Raupach, Tobias Zahn, Regina Eberle, Jacomine Krijnse-Locker, Michael Basic, Eberhard Hildt
Summary: A newly identified virion egress pathway of hepatitis B virus was found, where intact virions are released as exosomes. These exosomes act as a transporter, impacting the spread of the virus.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(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)
Article
Multidisciplinary Sciences
Diana P. Baquero, Anastasia D. Gazi, Martin Sachse, Junfeng Liu, Christine Schmitt, Maryse Moya-Nilges, Stefan Schouten, David Prangishvili, Mart Krupovic
Summary: Research on the enveloped Sulfolobus islandicus filamentous virus (SIFV) infecting hyperthermophilic archaea has revealed unique virion structures, assembly processes, and release mechanisms. The findings suggest distinct virus-host interaction systems in Archaea, diverging from those of bacteria and eukaryotes. By studying the life cycle of SIFV, insights have been gained into the intracellular assembly of virions and their release through large pyramidal portals, shedding light on the evolution of virus-host interactions in Archaea.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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
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
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
Cell Biology
Gemma Bogard, Johanna Barthelemy, Aline Hantute-Ghesquier, Valentin Sencio, Patricia Brito-Rodrigues, Karin Seron, Cyril Robil, Anne Flourens, Florence Pinet, Delphine Eberle, Francois Trottein, Martine Duterque-Coquillaud, Isabelle Wolowczuk
Summary: COVID-19 primarily affects the respiratory system, but it also has extrapulmonary manifestations. It has been found that SARS-CoV-2 can directly affect white adipose tissue (WAT), leading to insulin resistance and dyslipidemia. However, there is limited data on the impact of SARS-CoV-2 on WAT in older individuals. This study revealed that SARS-CoV-2 infection caused changes in adipocyte size and lipid metabolism in WAT, and older hamsters had a more severe response. Additionally, older hamsters showed difficulties in clearing dead adipocytes by macrophages, leading to the persistence of large adipose crown-like structures (CLSs).
CELL DEATH & DISEASE
(2023)
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
Marion Chambon, Charline Herrscher, Dana Al Halabi, Nathan Francois, Sandrine Belouzard, Stephanie Boutet, Van Cuong Pham, Thi Mai Huong Doan, Karin Seron, Patrick Mavingui, Marc Litaudon, Chaker El Kalamouni, Cecile Apel
Summary: The COVID-19 pandemic has highlighted the need for antivirals against coronaviruses. A study found that an ethyl acetate extract from the leaves of Clausena harmandiana showed significant activity against SARS-CoV-2, with two phenolic lipids inhibiting the virus. This suggests that phenolic lipids from Clausena harmandiana could be a potential source of new antiviral agents against coronaviruses.
Article
Virology
Lowiese Desmarets, Marion Millot, Marylene Chollet-Krugler, Joel Boustie, Charline Camuzet, Nathan Francois, Yves Rouille, Sandrine Belouzard, Sophie Tomasi, Lengo Mambu, Karin Seron
Summary: This study identifies four lichen compounds that exhibit antiviral activity against human coronaviruses, including SARS-CoV-2. One of these compounds, perlatolic acid, shows promising antiviral activity against SARS-CoV-2.
Article
Plant Sciences
Alice Miral, Solenn Ferron, Isabelle Rouaud, Dinmukhammed Slyambayev, Latifa Bousarghin, Charline Camuzet, Sandrine Belouzard, Karin Seron, Pierre Le Pogam, Sylvain Tranchimand, Sophie Tomasi
Summary: An endolichenic strain of Xylaria hypoxylon cultivated alone or in coculture with Dendrothyrium variisporum produced seven new bioactive eremophilane sesquiterpenes. Eremoxylarin I exhibited selective activity against methicillin-resistant Staphylococcus aureus and HCoV-229E.
JOURNAL OF NATURAL PRODUCTS
(2023)
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)