Article
Microbiology
Eva Maria Borst, Sarah Harmening, Saskia Sanders, Enrico Caragliano, Karen Wagner, Tihana Lenac Rovis, Stipan Jonjic, Jens Bernhard Bosse, Martin Messerle
Summary: In human cytomegalovirus (HCMV), the small capsid protein (SCP) plays an essential role in ensuring stable levels of major capsid protein (MCP) and their mutual dependence guarantees appropriate levels of the other respective protein. The study provides insights into the mechanism of capsid assembly and identifies SCP as a potential target for antiviral inhibitors.
Article
Chemistry, Multidisciplinary
Suzanne B. P. E. Timmermans, Alireza Ramezani, Toni Montalvo, Mark Nguyen, Paul van der Schoot, Jan C. M. van Hest, Roya Zandi
Summary: This study reports on the spontaneous and reversible size conversion of empty capsids of CCMV, which is mediated by a hydrophobic elastin-like polypeptide and pH jump. The conversion process from T = 1 to T = 3 is 10 times slower than that from T = 3 to T = 1. The experimental findings are explained using a simple model based on classical nucleation theory.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Medicinal
Scott D. Kuduk, Lindsey G. DeRatt, Bart Stoops, Paul Shaffer, Angela M. Lam, Christine Espiritu, Robert Vogel, Vincent Lau, Osvaldo A. Flores, George D. Hartman
Summary: The HBV capsid core protein plays crucial roles in the viral life cycle and is a potential drug target for treating chronic HBV infection. The optimization of diazepinone HBV CAMs, which interfere with capsid assembly, is described in this study.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Scott D. Kuduk, Bart Stoops, Angela M. Lam, Christine Espiritu, Robert Vogel, Vincent Lau, Klaus Klumpp, Osvaldo A. Flores, George D. Hartman
Summary: The HBV core protein plays multiple crucial roles in the viral life cycle, making it a promising drug target for chronic HBV infection. Modulation of HBV capsid assembly has shown effectiveness in early clinical trials through the use of small molecule capsid assembly modulators. The evolution and structure-activity relationship of a novel pyrazolo piperidine lead series into advanced oxadiazepinone HBV CAMs is described in this study.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Serena Calamaio, Marialaura Serzanti, Jennifer Boniotti, Annamaria Fra, Emirena Garrafa, Manuela Cominelli, Rosanna Verardi, Pietro Luigi Poliani, Silvia Dotti, Riccardo Villa, Giovanna Mazzoleni, Patrizia Dell'Era, Nathalie Steimberg
Summary: The process of developing a new drug is time-consuming and expensive, and hepatotoxicity is a major concern. Animal models have limitations due to interspecies differences, but human induced pluripotent stem cells (hiPSCs) offer new possibilities for drug testing. We miniaturized the process of generating hepatic organoids using hiPSC-derived mesenchymal stem cells, hepatocytes, and endothelial cells. These organoids were cultivated in vitro using static and dynamic cultures, and could be maintained for up to 1 week. This hiPSC-derived liver organoid model could potentially replace animal testing in pharmacological and toxicological studies.
Article
Multidisciplinary Sciences
Manish Gupta, Alexander J. Pak, Gregory A. Voth
Summary: Researchers use molecular dynamics simulations to reveal the molecular mechanism of HIV-1 capsid formation, including the role of IP6. This study shows that IP6 initially promotes curvature generation by trapping pentameric defects and shifts the assembly behavior towards kinetically favored outcomes. Additionally, IP6 can stabilize metastable capsid intermediates and induce structural pleomorphism in mature capsids.
Article
Multidisciplinary Sciences
Tobias P. Woerner, Antonette Bennett, Sana Habka, Joost Snijder, Olga Friese, Thomas Powers, Mavis Agbandje-McKenna, Albert J. R. Heck
Summary: Recent research on Adeno-associated viruses (AAVs) using high-resolution native mass spectrometry has revealed that the capsids of different AAV serotypes assemble stochastically, leading to a highly heterogeneous population of capsids with varying compositions. Even the most abundant VP stoichiometry represents only a small percentage of the total AAV population. The systematic scoring of simulations against experimental native MS data offers a sensitive new method to characterize these therapeutically important heterogeneous capsids.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Jingyuan Xi, Zhiqiang Gu, Chunyan Sun, Zimin Chen, Ting Zhang, Ran Chen, Tianyu Liu, Hao Liao, Jun Zou, Danli Yang, Qiang Xu, Jie Wang, Guochao Wei, Zhe Cheng, Fengmin Lu, Xiangmei Chen
Summary: QL-007, a small molecule compound, inhibits HBV replication by influencing the assembly of HBV core proteins, showing potential as an antiviral drug against HBV in preclinical studies and clinical trials.
ANTIVIRAL RESEARCH
(2023)
Article
Microbiology
Nadine Renner, Donna L. Mallery, K. M. Rifat Faysal, Wang Peng, David A. Jacques, Till Boecking, Leo C. James
Summary: HIV protects its RNA genome while copying it into DNA by constructing a capsid with highly charged pores that can import nucleotides, preventing host sensing and allowing DNA synthesis. The metabolite IP6 plays a crucial role in coordinating positively charged residues in the capsid, and mutations in K25 affect HIV infectivity and DNA synthesis.
Article
Pharmacology & Pharmacy
Yue Luo, Junjun Cheng, Zhanying Hu, Haiqun Ban, Shuo Wu, Nicky Hwang, John Kulp, Yuhuan Li, Yanming Du, Jinhong Chang, Usha Viswanathan, Ju-Tao Guo
Summary: The study identified critical Cp amino acid residues for capsid assembly, pgRNA encapsidation, and resistance to CpAMs through systematic mutagenesis analysis. Specific residues such as W102 and Y132 are crucial for capsid assembly, while other residues affect pgRNA encapsidation. Several mutant Cp support high levels of DNA replication but show strong resistance to CpAMs.
ANTIVIRAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Lindsey G. DeRatt, Bart Stoops, Paul Shaffer, Angela M. Lam, Christine Espiritu, Robert Vogel, Vincent Lau, Osvaldo A. Flores, Scott D. Kuduk
Summary: The capsid core protein of the HBV virus is essential for the persistence of chronic HBV infections. Disrupting the assembly of the capsid has shown promise in combating the virus, and a new series of di-fluoro azepane CAMs with exceptional properties has been described in this study.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Farzaneh Mohajerani, Botond Tyukodi, Christopher J. Schlicksup, Jodi A. Hadden-Perilla, Adam Zlotnick, Michael F. Hagan
Summary: In this study, computer simulations and analysis were used to reveal the assembly process of hepatitis B virus (HBV) and the mechanism of capsid polymorphism. The findings are important for understanding the HBV lifecycle and developing new antiviral drugs.
Article
Biochemical Research Methods
Maryam Parsian, Pelin Mutlu, Ender Yildirim, Can Ildiz, Can Ozen, Ufuk Gunduz
Summary: The study introduces a new tissue culture approach that combines a microfluidic chip with microdissected breast cancer tumors, maintaining the viability of tissue samples and enabling stable culturing of tumor tissues compared to conventional methods. This new culturing technique may have the potential to develop new treatment strategies more effectively.
Article
Chemistry, Physical
Elvira Tarasova, Noriaki Okimoto, Shanshan Feng, Dmitry Nerukh, Reza Khayat, Makoto Taiji
Summary: The study found that pure PCV2 capsid proteins require acidic conditions to assemble into empty capsids in vitro in the absence of nucleic acids. Molecular dynamics simulation revealed that an appropriate protonation configuration is necessary for driving capsid assembly, with assembly being prohibited at neutral pH due to electrostatic repulsion.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Multidisciplinary Sciences
Thais C. Neves-Martins, Nathane C. Mebus-Antunes, Carlos H. G. Neto, Glauce M. Barbosa, Fabio C. L. Almeida, Icaro P. Caruso, Andrea T. Da Poian
Summary: The researchers designed a mutant of the dengue virus capsid protein (DENVC) by replacing a positively charged spot with a cysteine residue, resulting in the self-assembly of capsid-like particles (CLP) in solution without nucleic acids.
Article
Virology
Naiqing Xu, Xinen Tang, Xin Wang, Miao Cai, Xiaowen Liu, Xiaolong Lu, Shunlin Hu, Min Gu, Jiao Hu, Ruyi Gao, Kaituo Liu, Yu Chen, Xiufan Liu, Xiaoquan Wang
Summary: This study found that the H9N2 subtype avian influenza virus has a high airborne transmissibility, while the H7N9 virus does not. The Hemagglutinin protein of the H9N2 virus was found to play a key role in replication, stability, and airborne transmission.
Article
Virology
Samar S. Ewies, Sabry M. Tamam, Ahmed S. Abdel-Moneim, Sherin R. Rouby
Summary: Contagious ecthyma (CE) is a highly contagious viral disease of sheep and goats worldwide. The study provided a clinical description of CE and screened for genetic variation in the B2L gene. Infected sheep exhibited anorexia and oral lesions, while inoculated chicken embryos showed pock lesions. The B2L gene was successfully amplified and found to be highly conserved.
Article
Virology
Yigal Farnoushi, Dan Heller, Avishai Lublin
Summary: In recent years, new variants of avian reovirus (ARV) have caused a variety of symptoms in chickens worldwide, including viral arthritis/tenosynovitis. This study analyzed emerging ARV variants in Israel and found significant genetic diversity. Most ARV isolates in Israel belonged to genotypic cluster 5 (GC5). The study suggests that Israel has not experienced the emergence of new ARV variants since the introduction of the live vaccine (ISR-7585), but ongoing monitoring is needed due to the continuous emergence of ARV variants.
Article
Virology
Shigeru Tajima, Michiyo Kataoka, Yuki Takamatsu, Hideki Ebihara, Chang-Kweng Lim
Summary: Yokose virus (YOKV), a bat-associated flavivirus, was found to replicate at a slower rate in mosquito cells compared to other mosquito-borne flaviviruses. Specific nucleotide mutations in the virus were identified to enhance its proliferation ability in mosquito cells.
Article
Virology
Alejandra Borjabad, Baojun Dong, Wei Chao, David J. Volsky, Mary Jane Potash
Summary: This study investigated HIV brain disease using a mouse model, and found that poly I:C can reverse associated cognitive impairment and reduce virus burden. The results also revealed transcriptional changes related to neuronal function and innate immune responses.
Article
Virology
Ching-Hung Lin, Feng-Cheng Hsieh, Meilin Wang, Chieh Hsu, Hsuan-Wei Hsu, Chun-Chun Yang, Cheng-Yao Yang, Hung-Yi Wu
Summary: This study demonstrates that the synthesis of coronavirus subgenomic mRNA is not solely determined by the sequence homology between the leader TRS and TRS-B, but also by the disassociation of the coronavirus polymerase from the viral genome. This finding provides a new insight into the transcription mechanism of coronaviruses.
Article
Virology
Nicholas S. Kron, Benjamin W. Neuman, Sathish Kumar, Patricia L. Blackwelder, Dayana Vidal, Delphina Z. Walker-Phelan, Patrick D. I. Gibbs, Lynne A. Fieber, Michael C. Schmale
Summary: Two recent studies documented the genome of a novel virus in marine animals, finding that the virus is widespread in apparently healthy animals but not highly expressed in neurons. The studies also identified viral replication factories and high levels of defective genomes in chronically infected animals.
Article
Virology
Andrew M. Ramey, Laura C. Scott, Christina A. Ahlstrom, Evan J. Buck, Alison R. Williams, Mia Kim Torchetti, David E. Stallknecht, Rebecca L. Poulson
Summary: We successfully detected and characterized highly pathogenic avian influenza viruses in hunter-harvested wild waterfowl samples from western Alaska. Genomic analysis revealed three independent viral introductions into Alaska. Our findings demonstrate the utility and potential limitations of using molecular processing approaches directly on original swab samples for viral research and monitoring.
Article
Virology
Ting Gong, Dongdong Wu, Yongzhi Feng, Xing Liu, Qi Gao, Xiaoyu Zheng, Zebu Song, Heng Wang, Guihong Zhang, Lang Gong
Summary: This study discovered that quercetin can inhibit PEDV replication both in vivo and in vitro, and alleviate the clinical symptoms and intestinal injury caused by the virus. This provides a new direction for the development of PED antiviral drugs.
Article
Virology
Min Zhu, Hao Zeng, Jianqiao He, Yaohui Zhu, Pingping Wang, Jianing Guo, Jinfan Guo, Huabo Zhou, Yifeng Qin, Kang Ouyang, Zuzhang Wei, Weijian Huang, Ying Chen
Summary: The reassortment between avian H9N2 and Eurasian avian-like (EA) H1N1 viruses may have potentially changed from avian-to-mammals adaptation. This study found that the introduction of EA H1N1 internal genes into H9N2 virus restored the replication capability and resulted in extreme virulence in some cases. This raises new concerns for public health due to the possible coexistence of H9N2 and EA H1N1 viruses in dogs.
