Article
Chemistry, Multidisciplinary
Victor K. Outlaw, Ross W. Cheloha, Eric M. Jurgens, Francesca T. Bovier, Yun Zhu, Dale F. Kreitler, Olivia Harder, Stefan Niewiesk, Matteo Porotto, Samuel H. Gellman, Anne Moscona
Summary: Lower respiratory tract infections in children globally are largely caused by parainfluenza viruses (HPIVs), with no available vaccines or effective treatments against these pathogens. Research has shown that lipopeptides derived from HPIV3 F can inhibit infection, and the modification of the peptide backbone with beta-amino acid residues has resulted in improved antiviral activity and in vivo stability.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Microbiology
Victoria Ortega, J. Lizbeth Reyes Zamora, I. Abrrey Monreal, Daniel T. Hoffman, Shahrzad Ezzatpour, Gunner P. Johnston, Erik M. Contreras, Fernando J. Vilchez-Delgado, Hector C. Aguilar
Summary: This study uncovers new mechanisms by which the G stalk and its mobility modulate the triggering of F and also unexpectedly affect a very late step in membrane fusion, namely fusion pore expansion. These novel findings may extend to other paramyxoviruses, offering new potential targets for therapeutic interventions.
Article
Chemistry, Physical
Amy Lam, Daniel S. Yuan, Samir H. Ahmed, Robert J. Rawle
Summary: Binding to the host membrane is the initial infection step for animal viruses. This study found that the distribution of viral sizes and the lateral distribution of receptors play a mechanistic role in viral infection.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Medicine, Research & Experimental
Alexander L. Greninger, Ksenia Rybkina, Michelle J. Lin, Jennifer Drew-Bear, Tara C. Marcink, Ryan C. Shean, Negar Makhsous, Michael Boeckh, Olivia Harder, Francesca Bovier, Shana R. Burstein, Stefan Niewiesk, Bert K. Rima, Matteo Porotto, Anne Moscona
Summary: Respiratory viruses have the ability to evolve within the respiratory tract under the selective pressure of the host environment or drug treatment. Long-term infections in immunocompromised hosts lead to viral evolution and development of infectious variants. In chronic human parainfluenza virus 3 (HPIV3) infection, mutations favoring viral entry and persistence were observed, suggesting potential evolution of viruses to alter their biophysical characteristics to persist in the face of host-directed therapeutics.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Multidisciplinary Sciences
Tara C. Marcink, Gillian Zipursky, Wenjing Cheng, Kyle Stearns, Shari Stenglein, Kate Golub, Frances Cohen, Francesca Bovier, Daniel Pfalmer, Alexander L. Greninger, Matteo Porotto, Amedee des Georges, Anne Moscona
Summary: This study used cryo-electron tomography to visualize the fusion complex of human parainfluenza virus 3, revealing the mechanism of fusion and potential druggable targets for paramyxoviruses.
Review
Virology
Pablo Guardado-Calvo, Felix A. Rey
Summary: The fusion of viral and cell lipid bilayers is a key step in the entry of enveloped viruses into cells, driven by a dedicated membrane fusion protein located on the virion surface. Class II fusion machinery consists of two glycoproteins that fold together in the ER of infected cells to avoid premature fusion. Despite diverging in 3D fold during evolution, class II accompanying proteins also derive from a common ancestor and play different functional roles.
Review
Clinical Neurology
Elisa Cali, Clarissa Rocca, Vincenzo Salpietro, Henry Houlden
Summary: SNAREs are a heterogeneous family of proteins involved in synaptic vesicle exocytosis and transmission, with mutations in associated genes leading to a spectrum of neurological conditions known as SNAREopathies. These conditions range from simple febrile seizures to severe early-onset epileptic encephalopathies. Research focuses on the core SNARE proteins and related regulators in delineating epileptic phenotypes.
FRONTIERS IN NEUROLOGY
(2022)
Review
Virology
Charles J. Russell, Julia L. Hurwitz
Summary: This study reviews the development of Sendai virus (SeV) as a versatile pediatric vaccine targeting various respiratory viruses, with positive results from clinical trials completed. Collaborative efforts with multiple institutions have advanced further development of the vaccine, showing promising prospects for successful application in infants.
Article
Multidisciplinary Sciences
Vidya Mangala Prasad, Jelle S. Blijleven, Jolanda M. Smit, Kelly K. Lee
Summary: In this study, time-resolved cryo-electron tomography and subtomogram averaging were used to capture the 3D organization and population evolution of intermediates during membrane fusion of CHIKV, a medically important alphavirus. The findings provide important insights into the mechanism of virus entry into cells and virus biology.
NATURE COMMUNICATIONS
(2022)
Article
Engineering, Electrical & Electronic
Yong Wang, Xinhui Liu, Quanxiao Zhao, Haiteng He, Zongwei Yao
Summary: This article presents a research on road target detection based on deep learning by combining image data of vision with point cloud data from light detection and ranging (LiDAR). The proposed approach utilizes a MY3Net network, which integrates Mobilenet v2 and YOLO v3, to detect RGB images and densified depth maps. A decision-level fusion model is proposed to integrate the detection results of RGB images and depth maps. Experimental results show high detection accuracy even under complex illumination conditions.
IEEE SENSORS JOURNAL
(2023)
Article
Multidisciplinary Sciences
Ramon Martinez-Mamol, Rosina Giordano-Santini, Eva Kaulich, Ann-Na Cho, Magdalena Przybyla, Md Asrafuzzaman Riyadh, Emilija Robinson, Keng Yih Chew, Rumelo Amor, Frederic A. Meunier, Giuseppe Balistreri, Kirsty R. Short, Yazi D. Ke, Lars M. Ittner, Massimo A. Hilliard
Summary: Viruses, including SARS-CoV-2, can infect the brain and cause severe neurological symptoms through the fusion of neurons and glia. This fusion is mediated by the viral fusogen and leads to the formation of multicellular syncytia, as well as the spread of molecules and organelles. Furthermore, the fusion severely compromises neuronal activity. These findings contribute to our understanding of the mechanisms by which viruses affect the nervous system and cause neuropathology.
Article
Biophysics
Geunseon Park, Jong-Woo Lim, Chaewon Park, Minjoo Yeom, Sojeong Lee, Kwang-Soo Lyoo, Daesub Song, Seungjoo Haam
Summary: Cell-mimetic nanoparticles (CMPs) developed in this study can rapidly detect highly pathogenic avian influenza viruses (HPAIVs) and low pathogenic avian influenza viruses (LPAIVs). This method has the potential to be an efficient diagnostic tool for early detection of viruses, preventing economic losses associated with viral outbreaks.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Medicine, Research & Experimental
Helen M. Parrington, Nurgun Kose, Erica Armstrong, Laura Handal, Summer Diaz, Joseph Reidy, Jinhui Dong, Guillaume B. E. . Stewart-Jones, Punya Shrivastava-Ranjan, Shilpi Jain, Cesar G. Albarino, Robert H. Carnahan, James E. Crowe
Summary: Research has found that antibodies against SOSV can neutralize the virus, with antibodies targeting the attachment protein showing higher potency. This provides insights into the mechanisms of human immune response to SOSV and the molecular basis of antibody recognition.
Article
Biochemistry & Molecular Biology
Li Zhang, Jiyuan Zou, Zhihao Wang, Lin Li
Summary: Long non-coding RNAs (lncRNAs) have emerged as critical regulators in controlling gene expression in cell differentiation and development, particularly during the process of follicle maturation. This study shows that the expression of lncRNAs is more specific than protein-coding genes in both follicles and granulosa cells, indicating their crucial role in follicle development. By analyzing subpathways and clustering target genes based on their expression similarity, the diverse regulatory functions of lncRNAs during primordial follicle activation (PFA) were revealed. Knockdown experiments further validated the regulatory functions of specific lncRNAs in specific subpathways. Overall, this study emphasizes the importance of subpathway analysis in understanding the functions of lncRNAs during PFA and opens new avenues for future research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Evgeniia A. Diatlova, Grigory V. Mechetin, Anna V. Yudkina, Vasily D. Zharkov, Natalia A. Torgasheva, Anton V. Endutkin, Olga V. Shulenina, Andrey L. Konevega, Irina P. Gileva, Sergei N. Shchelkunov, Dmitry O. Zharkov
Summary: The protein encoded by the D4R gene in vaccinia virus has both base excision repair uracil-DNA N-glycosylase (vvUNG) activity and acts as a processivity factor in the viral replication complex. The processivity of vvUNG has been characterized using the correlated cleavage assay, which suggests that it plays a role in lesion search through one-dimensional diffusion. Inhibitors carrying a tetrahydro-2,4,6-trioxopyrimidinylidene moiety can suppress the processivity of vvUNG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Nicole A. P. Lieberman, Vikas Peddu, Hong Xie, Lasata Shrestha, Meei-Li Huang, Megan C. Mears, Maria N. Cajimat, Dennis A. Bente, Pei-Yong Shi, Francesca Bovier, Pavitra Roychoudhury, Keith R. Jerome, Anne Moscona, Matteo Porotto, Alexander L. Greninger
Article
Microbiology
Tara C. Marcink, Tong Wang, Amedee des Georges, Matteo Porotto, Anne Moscona
Article
Biochemical Research Methods
Ana Luisa Rodrigues Toste de Carvalho, Hsiao-Yun Liu, Ya-Wen Chen, Matteo Porotto, Anne Moscona, Hans-Willem Snoeck
Summary: This protocol details a method for direct differentiation of human pluripotent stem cells into various mature lung and airway cell types using a 3D collagen I matrix. The resulting cultures have potential applications in regenerative medicine, lung disease modeling, drug screening, and studying human lung development.
Article
Multidisciplinary Sciences
Rory D. de Vries, Katharina S. Schmitz, Francesca T. Bovier, Camilla Predella, Jonathan Khao, Danny Noack, Bart L. Haagmans, Sander Herfst, Kyle N. Stearns, Jennifer Drew-Bear, Sudipta Biswas, Barry Rockx, Gael McGill, N. Valerio Dorrello, Samuel H. Gellman, Christopher A. Alabi, Rik L. de Swart, Anne Moscona, Matteo Porotto
Summary: The lipopeptide fusion inhibitors designed effectively blocked the critical first step of SARS-CoV-2 infection. Daily intranasal administration to ferrets prevented transmission completely, showcasing potential as safe and effective prophylaxis for reducing SARS-CoV-2 transmission.
Editorial Material
Immunology
Cyrille Mathieu, Marion Ferren, Olivia Harder, Francesca T. Bovier, Tara C. Marcink, Camilla Predella, Fabrizio Angius, Jennifer Drew-Bear, N. Valerio Dorrello, Alex L. Greninger, Anne Moscona, Stefan Niewiesk, Branka Horvat, Matteo Porotto
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Victor K. Outlaw, Ross W. Cheloha, Eric M. Jurgens, Francesca T. Bovier, Yun Zhu, Dale F. Kreitler, Olivia Harder, Stefan Niewiesk, Matteo Porotto, Samuel H. Gellman, Anne Moscona
Summary: Lower respiratory tract infections in children globally are largely caused by parainfluenza viruses (HPIVs), with no available vaccines or effective treatments against these pathogens. Research has shown that lipopeptides derived from HPIV3 F can inhibit infection, and the modification of the peptide backbone with beta-amino acid residues has resulted in improved antiviral activity and in vivo stability.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
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.
Article
Microbiology
Cyrille Mathieu, Francesca T. Bovier, Marion Ferren, Nicole A. P. Lieberman, Camilla Predella, Alexandre Lalande, Vikas Peddu, Michelle J. Lin, Amin Addetia, Achchhe Patel, Victor Outlaw, Barbara Corneo, N. Valerio Dorrello, Thomas Briese, Diana Hardie, Branka Horvat, Anne Moscona, Alexander L. Greninger, Matteo Porotto
Summary: The study found that a single amino acid change in the fusion protein (F) of measles virus (MeV) can enhance the virus's ability to spread in the central nervous system, leading to serious complications. Furthermore, the research showed that virus spread in brain tissue can be blocked by an inhibitory peptide targeting the F protein.
Article
Microbiology
Debora Stelitano, Stuart P. Weisberg, Monica P. Goldklang, Yun Zhu, Francesca T. Bovier, Gavreel F. Kalantarov, Giuseppe Greco, Didier Decimo, Gianluigi Franci, Michele Cennamo, Giuseppe Portella, Massimiliano Galdiero, Cyrille Mathieu, Branka Horvat, Ilya N. Trakht, Anne Moscona, Michael A. Whitt, Matteo Porotto
Summary: This study introduces a new platform strategy for assessing virus-neutralizing activity and a cell-based immunofluorescent assay to accurately measure the neutralization potential of antibodies, providing useful tools for evaluating antiviral immunity acquired through natural infection or vaccination.
Article
Microbiology
Allison N. Tucker, Travis J. Carlson, Aurijit Sarkar
Summary: The development of novel drugs to treat diseases caused by intracellular bacterial pathogens faces challenges such as understanding the nature of chemicals that can penetrate bacterial cells, lack of publicly available information on virulence factors, and the need for advanced technologies in experimental investigation. Overcoming these hurdles will significantly advance drug discovery against intracellular bacterial pathogens.
Article
Biochemistry & Molecular Biology
Patricia M. Silva, Marcelo T. Augusto, Matteo Porotto, Nuno C. Santos
Summary: Influenza viruses cause respiratory diseases with high morbidity and mortality worldwide. Current antiviral strategies are limited by viral mutations, highlighting the need for new approaches. This study evaluated HA-derived peptides and found that they may interfere with viral fusion by binding to cell membranes, offering potential for new influenza virus inhibitors.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Microbiology
Laurine C. Rijsbergen, Katharina S. Schmitz, Lineke Begeman, Jennifer Drew-Bear, Lennert Gommers, Mart M. Lamers, Alexander L. Greninger, Bart L. Haagmans, Matteo Porotto, Rik L. de Swart, Anne Moscona, Rory D. de Vries
Summary: This study evaluated the infection and transmission of HPIV-3 in ferrets and found that ferrets are naturally susceptible to HPIV-3 infection, but the infection is limited and does not cause overt clinical signs or ferret-to-ferret transmission.
Article
Microbiology
Katharina S. Schmitz, Daryl Geers, Rory D. de Vries, T. Francesca Bovier, Anna Z. Mykytyn, Corine H. Geurts van Kessel, Bart L. Haagmans, Matteo Porotto, Rik L. de Swart, Anne Moscona
Summary: SARS-CoV-2 continues to spread globally, with new variants that evade immunity generated by vaccines and previous strains. Fusion-inhibitory peptides may provide an intervention strategy that is not affected by viral evolution.
Article
Chemistry, Multidisciplinary
Rui Su, Jin Zeng, Tara C. Marcink, Matteo Porotto, Anne Moscona, Ben O'Shaughnessy
Summary: SARS-CoV-2 enters cells by unleashing the spike fusion intermediate, which undergoes giant fluctuations to capture target cells and may trigger refolding. A computational model of the fusion intermediate (FI) was constructed based on known structures of SARS-CoV-2. Molecular dynamics simulations revealed that the FI is highly flexible and exhibits large bending and extensional fluctuations due to three hinges at the C-terminal base. The simulated configurations are consistent with recent cryo-electron tomography measurements. The FI utilizes massive configurational fluctuations for efficient membrane capture and may provide potential drug targets.
ACS CENTRAL SCIENCE
(2023)
Article
Immunology
Stuart P. Weisberg, Thomas J. Connors, Yun Zhu, Matthew R. Baldwin, Wen-Hsuan Lin, Sandeep Wontakal, Peter A. Szabo, Steven B. Wells, Pranay Dogra, Joshua Gray, Emma Idzikowski, Debora Stelitano, Francesca T. Bovier, Julia Davis-Porada, Rei Matsumoto, Maya Meimei Li Poon, Michael Chait, Cyrille Mathieu, Branka Horvat, Didier Decimo, Krystalyn E. Hudson, Flavia Dei Zotti, Zachary C. Bitan, Francesca La Carpia, Stephen A. Ferrara, Emily Mace, Joshua Milner, Anne Moscona, Eldad Hod, Matteo Porotto, Donna L. Farber
Summary: This study found distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts showed a broader range of antibody responses, while children predominantly generated antibodies specific for the S protein and had reduced neutralizing activity compared to adults.