Review
Chemistry, Multidisciplinary
Bo Kyeong Yoon, Won-Yong Jeon, Tun Naw Sut, Nam-Joon Cho, Joshua A. Jackman
Summary: This review highlights the importance of membrane-enveloped viruses and discusses the latest progress in developing novel membrane-targeting virus inhibition strategies with nanotechnology. These efforts have the potential to support the development of next-generation antiviral drug candidates and technologies, and to strengthen capabilities for virus pandemic preparedness.
Article
Chemistry, Medicinal
Zhenyu Li, Tian Li, Meisui Liu, Tijana Ivanovic
Summary: Understanding mechanisms of resistance to antiviral inhibitors can lead to improved strategies for inhibitor design. This study found that stabilizing mutations in the fusion peptide make the virus more sensitive to Arbidol, while destabilizing mutations make the virus resistant. Fusion-peptide destabilization leads to resistance, even without reduced Arbidol binding to the virus. Arbidol increases the free-energy cost for fusion-peptide release, explaining the observed resistance.
ACS INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Joshua A. Jackman
Summary: This mini-review covers the latest efforts to develop membrane-targeting antiviral peptides that inhibit enveloped viruses by preventing virus-cell fusion or disrupting the viral membrane envelope. Mechanisms of antiviral activity and peptide engineering strategies are discussed, with application examples demonstrating their usefulness in animal models. A stronger emphasis on biophysical concepts is proposed to refine mechanistic understanding and support potential clinical translation.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Article
Microbiology
Wooil Choi, Yang-Hoon Kim, Jiho Min
Summary: The study assesses the vacuoles isolated from the yeast Saccharomyces cerevisiae as green antiviral agents to decrease the concerns about massive use of chemical antiviral agents and its side effects. Using vacuole treatment can effectively reduce viral infectivity. This approach is environmentally friendly and cost-effective.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Medicinal
Matthew R. Freidel, Roger S. Armen
Summary: Umifenovir (Arbidol) shows efficacy as a monotherapy for COVID-19 and has synergistic inhibition with other antivirals. Derivatives with substitutions at C-4 and C-6 positions show modest improvement, but are still only partial inhibitors. Atomic resolution modeling of fusion inhibitor binding and molecular mechanism implications are discussed based on experimental structures of Spike protein.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Review
Biochemistry & Molecular Biology
Sai Li
Summary: This article reviews the recent advances in the applications of cryo-electron tomography (cryo-ET) on enveloped viral structures and intracellular viral activities.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Aditya K. Padhi, Aniruddha Seal, Javed Masood Khan, Maqusood Ahamed, Timir Tripathi
Summary: Research suggests that the anti-influenza drug arbidol has an advantage in inhibiting the coronavirus, with potential better treatment outcomes for patients. Molecular dynamics simulations show that arbidol binds and stabilizes at the receptor-binding domain (RBD)/ACE2 interface with increased affinity between RBD and ACE2 in the arbidol-bound complex, suggesting favorable interactions that limit structural rearrangements associated with membrane fusion and virus entry.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Xiangyang Guo, Jan Steinkuehler, Mariana Marin, Xiang Li, Wuyuan Lu, Rumiana Dimova, Gregory B. Melikyan
Summary: IFITM3 inhibits the transition from hemifusion to full fusion by inducing negative membrane curvature and increasing membrane order and stiffness, thus blocking the entry of diverse enveloped viruses.
Article
Chemistry, Multidisciplinary
Francesca T. Bovier, Ksenia Rybkina, Sudipta Biswas, Olivia Harder, Tara C. Marcink, Stefan Niewiesk, Anne Moscona, Christopher A. Alabi, Matteo Porotto
Summary: An antiviral peptide targeting the Measles virus fusion protein has been developed, showing high potency and minimal cytotoxicity in vitro. The chemical conjugation of FIP and HRC-derived peptides resulted in increased antiviral activity, with promising potential as a measles virus antiviral agent via specific targeting and stabilization of the prefusion MeV F structure.
Review
Immunology
Yue Kang, Yin Shi, Silu Xu
Summary: Influenza virus infection is a lethal disease with high morbidity and mortality, and the lack of effective antiviral drugs has worsened the problem. Arbidol (ARB) is a promising broad-spectrum antiviral drug that inhibits several viruses and has a high safety profile.
IMMUNITY INFLAMMATION AND DISEASE
(2023)
Article
Plant Sciences
Lianghao Huang, Jinyu Wang, Xiaoyao Ma, Lishan Sun, Cui Hao, Wei Wang
Summary: The study found that Piceatannol (PIC) has significant anti-influenza virus activity both in vitro and in vivo, mainly by interacting with HA to block membrane fusion and inhibit viral infection.
Article
Multidisciplinary Sciences
Yuta Shirogane, Hidetaka Harada, Yuichi Hirai, Ryuichi Takemoto, Tateki Suzuki, Takao Hashiguchi, Yusuke Yanagi
Summary: Measles virus (MeV) can persist in the brain and cause subacute sclerosing panencephalitis (SSPE). Mutations in the fusion (F) protein of persisting MeVs enhance its fusogenicity, but paradoxically, some mutations that reduce fusogenicity may be selected alongside the wild-type MeV genome. The presence of SSPE-derived substitutions in the F protein affects its fusogenicity, which can be enhanced or abolished by coexpression with the wild-type F protein. These findings provide insights into the long-term neuropathogenic process of MeV and the relationships between genotype and phenotype in en bloc transmitted viruses.
Review
Biochemistry & Molecular Biology
Alzbeta Tuerkova, Peter M. Kasson
Summary: Computational methods, especially molecular dynamics simulations, have become important for studying viral infection mechanisms, but the complexity of virus-host interactions at large molecular scales presents challenges. A multiresolution strategy may offer a good balance between computational efficiency and physical fidelity.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Muhammed Muhsin Varikkodan, Chun-Chung Chen, Tzong-Yuan Wu
Summary: Chikungunya virus (CHIKV) is a global threat due to its high contagion rate and lack of effective remedies. Two BEVS-based approaches were developed to screen anti-CHIKV drugs, with one involving cell fusion in insect cells and the other using a replicon system in human cells to identify potential inhibitory compounds. The results suggest that BEVS could be a valuable tool for drug screening against CHIKV.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Brian B. Gowen, Shibani Naik, Jonna B. Westover, Eric R. Brown, Vidyasagar R. Gantla, Alexandra Fetsko, Ashley L. Dagley, Dallan J. Blotter, Nicole Anderson, Ken McCormack, Greg Henkel
Summary: The novel broad-spectrum arenavirus fusion inhibitors, ARN-75039 and ARN-75041, showed promising antiviral activity and pre-clinical development, demonstrating significant prophylactic and therapeutic effects in animal models of arenavirus infection.
ANTIVIRAL RESEARCH
(2021)
Article
Oncology
Audrey Page, Emilie Laurent, Didier Negre, Caroline Costa, Veronique Pierre, Thierry Defrance, Francois-Loic Cosset, Floriane Fusil
Summary: This study introduces a novel experimental approach for adoptive transfer of gene-edited B cells in humanized immune system mice, bypassing the risk of xenogeneic graft-versus-host reaction and closely mimicking human immune responses for potential clinical applications. Results show that the transduced B cells post-transfer in recipient's spleens are comparable to pre-immune B cell populations specific for certain protein antigens in mice, suggesting the potential for eliciting significant immune responses upon immunization.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Akaash K. Mishra, Jan Hellert, Natalia Freitas, Pablo Guardado-Calvo, Ahmed Haouz, J. Maximilian Fels, Daniel P. Maurer, Dafna M. Abelson, Zachary A. Bornholdt, Laura M. Walker, Kartik Chandran, Francois-Loic Cosset, Jason S. McLellan, Felix A. Rey
Summary: This study reveals the structure and neutralization mechanism of the Crimean-Congo hemorrhagic fever virus membrane fusion glycoprotein Gc, providing important molecular insights for the development of virus-specific medical countermeasures.
Article
Biochemistry & Molecular Biology
Francesca De Giorgi, Muhammed Bilal Abdul-Shukkoor, Marianna Kashyrina, Leslie-Ann Largitte, Francesco De Nuccio, Brice Kauffmann, Alons Lends, Florent Laferriere, Sebastien Bonhommeau, Dario Domenico Lofrumento, Luc Bousset, Erwan Bezard, Thierry Buffeteau, Antoine Loquet, Francois Ichas
Summary: The distinct neuropathological features and inclusion bodies in different alpha-Synucleinopathies reflect the strain diversity of invasive alpha-Syn amyloids. However, the contribution of non-amyloid factors to specific diseases is still uncertain. In Multiple System Atrophy, alpha-Syn inclusions in oligodendrocytes seem to result from the storage of amyloid aggregates pre-assembled in neurons. These inclusions originate from unique molecular properties or other factors dysregulated in MSA.
Article
Agricultural Engineering
Estelle Morvan, Brice Kauffmann, Axelle Grelard, Antoine Loquet, Anne-Julie Dixon, Erick J. Dufourc, Denis Rontein
Summary: This study reports a new eco-responsible method to produce (E)-(R)-4-thujanol crystals on a kilogram scale, which may open up new opportunities for the flavor, fragrance and pharmaceutical industries.
INDUSTRIAL CROPS AND PRODUCTS
(2022)
Article
Chemistry, Multidisciplinary
Lea Marie Becker, Melanie Berbon, Alicia Vallet, Axelle Grelard, Estelle Morvan, Benjamin Bardiaux, Roman Lichtenecker, Matthias Ernst, Antoine Loquet, Paul Schanda
Summary: Aromatic side chains play a significant role in protein plasticity and protein-protein interactions. Through isotope-labeling and NMR techniques, we studied the behavior of aromatic residues in two structurally homologous amyloid fibrils. We found that the hydrophobic amyloid core is rigid, while aromatic residues on the fibril surface undergo ring flips. This insight provides a better understanding of the conformational heterogeneity in amyloid cross-beta architecture.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Estelle Morvan, Nada Taib-Maamar, Axelle Grelard, Antoine Loquet, Erick J. Dufourc
Summary: Since the 1970s, the concept of biological membranes has become more diverse and dynamic. Solid-state NMR can be used to study the movement of membranes from picoseconds to seconds. Various factors such as order parameters, phase transitions, correlation times, activation energies, and membrane elasticity can be determined using motionally averaged spectra and relaxation times. Sterols play a role in modulating membrane properties and dynamics, reducing the impact of environmental changes on molecular order and dynamics. Large-scale membrane dynamics can be seen as a way to adapt to evolutionary constraints.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2023)
Article
Biochemistry & Molecular Biology
Fanfan Zhao, Yongfen Xu, Na Liu, Dawei Lv, Yujie Chen, Zhi Liu, Xia Jin, Mingbing Xiao, Dimitri Lavillette, Jin Zhong, Ralf Bartenschlager, Gang Long
Summary: This study developed a rigorous method to study extracellular vesicles (EVs) from Zika virus (ZIKV)-infected cells. The EVs did not transmit infection, but displayed abundant E proteins which have an antigenic landscape similar to that of virions. These results suggest that modulation of E protein release via virions and EVs may present a new approach to regulating flavivirus-host interactions.
Article
Gastroenterology & Hepatology
Julie Lucifora, Dulce Alfaiate, Caroline Pons, Maud Michelet, Ricardo Ramirez, Floriane Fusil, Fouzia Amirache, Axel Rossi, Anne-Flore Legrand, Emilie Charles, Serena Vegna, Rayan Farhat, Michel Rivoire, Guillaume Passot, Nicolas Gadot, Barbara Testoni, Charlotte Bach, Thomas F. Baumert, Anastasia Hyrina, Rudolf K. Beran, Fabien Zoulim, Andre Boonstra, Hildegard Buening, Eloi R. Verrier, Francois-Loic Cosset, Simon P. Fletcher, Anna Salvetti, David Durantel
Summary: This study elucidates the molecular mechanisms underlying how HDV interferes with HBV in patients with chronic coinfection. The researchers found that HDV induces the expression of interferon-stimulated genes (ISGs), and these genes are upregulated in HDV/HBV-coinfected patients. Inhibiting the hepatocyte's response to interferon partially restores the levels of HBV.
JOURNAL OF HEPATOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Alejandro Villalta, Batoul Srour, Audrey Lartigue, Martin Clemancey, Deborah Byrne, Florence Chaspoul, Antoine Loquet, Bruno Guigliarelli, Genevieve Blondin, Chantal Abergel, Benedicte Burlat
Summary: Scientists have discovered a protein in the giant virus mimivirus that is rich in the amino acids glycine and cysteine. This protein, called GciS, is one of the most abundant proteins in the viral particles and is likely essential for infection. It has unique binding properties with iron and inorganic sulfide.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Chelsea M. Brown, Robin A. Corey, Axelle Grelard, Ya Gao, Yeol Kyo Choi, Emanuel Luna, Martine Gilleron, Nicolas Destainville, Jerome Nigou, Antoine Loquet, Elizabeth Fullam, Wonpil Im, Phillip J. Stansfeld, Matthieu Chavent
Summary: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB) and is responsible for millions of deaths each year. The current treatment for TB is lengthy and expensive, and missed doses contribute to drug resistance. Understanding the structure and function of the Mtb cell envelope, particularly the plasma membrane, is crucial for developing new anti-TB drugs and improving treatment outcomes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Analytical
Estelle Morvan, Nada Taib-Maamar, Axelle Grelard, Antoine Loquet, Erick J. Dufourc
Summary: Understanding the membrane dynamics of complex systems is crucial to understanding their function. This study explores NMR methods to filter highly mobile molecular parts from more restricted environments. The researchers developed a quantitative MAS C-13 NMR approach coupled with CP and/or INEPT techniques to study rigid and fluid model membranes. They found that INEPT can detect only very mobile lipid headgroups in gel phases, while CP is required to detect the rigid parts. The study also reveals the potential of C-13 NMR chemical shift to monitor order-disorder phase transitions and provide information about membrane dynamics without isotopic labeling.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Huu Trong Phan, Victor Passos Gibson, Aurore Guedin, Emmanuel Ibarboure, Nadia El Mammeri, Axelle Grelard, Jean-Francois Le Meins, Erick J. Dufourc, Antoine Loquet, Suzanne Giasson, Jeanne Leblond Chain
Summary: It has been found that using conformationally pH-switchable lipids can greatly improve the cytosolic drug delivery of lipid vesicles. Understanding how these pH-switchable lipids disrupt the lipid assembly of nanoparticles and trigger cargo release is vital for optimizing their design. By combining morphological observations, physicochemical characterization, and phase behavior studies, we propose a mechanism of pH-triggered membrane destabilization. It is demonstrated that the switchable lipids are uniformly incorporated with other co-lipids and promote a temperature-insensitive liquid-ordered phase. The protonation of these switchable lipids upon acidification leads to conformational changes, causing fluctuations and local defects in the lipid vesicles and ultimately affecting the membrane permeability and cargo release.
Article
Immunology
Huguette Simo Tchetgna, Francine S. Yousseu, Francois-Loic Cosset, Natalia Bezerra de Freitas, Basile Kamgang, Philip J. McCall, Roland Ndip Ndip, Vincent Legros, Charles S. Wondji
Summary: This study aimed to determine the prevalence of CCHFV in domestic ruminants and its vector ticks in Cameroon. CCHFV-specific antibodies were detected in the plasma samples of cattle, sheep, and goats, and ticks were screened for the presence of the virus. The seroprevalence of CCHFV was highest in cattle (98.18%) and one CCHFV strain was identified in ticks collected from cattle.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Microbiology
Christelle Granier, Johan Toesca, Chloe Mialon, Maureen Ritter, Natalia Freitas, Bertrand Boson, Eve-Isabelle Pecheur, Francois-Loic Cosset, Solene Denolly
Summary: Hepatitis C virus (HCV) particles are stable when secreted from cells, but become highly unstable after freeze-thawing of producer cells. Cell-secreted proteins can protect HCV particles from degradation, specifically those that are lipidated and low-density. HCV particles are sensitive to oxidation, but can be protected from lipid oxidation by secreted factors.
Review
Biology
Natalia Freitas, Vincent Legros, Francois-Loic Cosset
Summary: Tick-borne infectious diseases, including Crimean-Congo hemorrhagic fever virus (CCHFV), pose a serious threat to public health. Although CCHF had not been reported in western Europe, high seropositivity rates in wildlife and detection of multiple strains of CCHFV in ticks in Spain indicate the establishment of an enzootic cycle in some areas of southwestern Europe. Currently, there are no approved therapeutic options or vaccines for the treatment of CCHFV.
COMPTES RENDUS BIOLOGIES
(2022)