Review
Chemistry, Medicinal
Zhaoyu Chen, Qinghua Cui, Michael Caffrey, Lijun Rong, Ruikun Du
Summary: This review summarizes the latest advances in the development of small molecule inhibitors targeting HA, including the structural basis and mode of action of these inhibitors, and looks forward to the development of more potent anti-influenza drugs in the future.
Article
Pharmacology & Pharmacy
Ruikun Du, Han Cheng, Qinghua Cui, Norton P. Peet, Irina N. Gaisina, Lijun Rong
Summary: A novel antiviral agent, CBS1194, specific to group 2 IAVs was identified through high-throughput screening, showing potential as a lead compound for further development.
ANTIVIRAL RESEARCH
(2021)
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)
Review
Biochemistry & Molecular Biology
Mariangela Agamennone, Marialuigia Fantacuzzi, Giovanni Vivenzio, Maria Carmina Scala, Pietro Campiglia, Fabiana Superti, Marina Sala
Summary: Influenza viruses are a major cause of high morbidity and mortality worldwide. Current approaches for fighting flu include seasonal vaccines and antiviral drugs, but they have limitations. Due to the highly mutative nature of influenza viruses, there is an urgent need for the development of new antiviral therapies, and peptide-based therapies show great promise.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Biology
Thitiya Boonma, Nattharuja Soikudrua, Bodee Nutho, Thanyada Rungrotmongkol, Nadtanet Nunthaboot
Summary: This study investigated the molecular binding mechanism of arbidol and its derivative with HA of H3N2 influenza virus. The results showed that the derivative could form stronger hydrogen bonds with HA amino acids compared to arbidol, resulting in higher inhibitory potency.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Oliver F. Harder, Sarah V. Barrass, Marcel Drabbels, Ulrich J. Lorenz
Summary: Microsecond time-resolved cryo-EM allows for observation of fast protein dynamics, as demonstrated by the contraction of the CCMV capsid induced by a pH jump.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Xueyong Zhu, Julianna Han, Weina Sun, Eduard Puente-Massaguer, Wenli Yu, Peter Palese, Florian Krammer, Andrew B. Ward, Ian A. Wilson
Summary: Broadly protective antibodies targeting conserved regions of the influenza virus hemagglutinin (HA) have the potential to generate universal influenza immunity. The study validates the potential of two chimeric HAs, cH4/3 and cH15/3, as universal vaccine immunogens. In addition to targeting the conserved HA stem, the chimeric HAs may also be able to elicit antibodies against the conserved trimer interface in the HA head domain.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Michael Caffrey, Arnon Lavie
Summary: This review discusses the critical role of influenza virus membrane protein HA in the viral life cycle, as well as its conformational changes and potential therapeutic strategies in response to pH changes in the endosomal compartment.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Chemistry, Medicinal
Liang Shao, Yangqing Su, Yuan Zhang, Fan Yang, Jihong Zhang, Tao Tang, Fei Yu
Summary: The influenza pandemic is a global public health challenge, especially for vulnerable and immunocompromised individuals. Designing effective drugs to inhibit the highly infectious and genetically variable influenza virus is difficult. However, previous studies have shown that oleanolic acid (OA) and its derivatives can block interactions between the virus and host cells, making them potential antiviral agents. In this study, a series of OA nonamers were synthesized and evaluated for their antiviral activities. Compound 15 was found to have the highest potency, comparable to the antiviral drug oseltamivir, and demonstrated activity against both influenza A and B viruses. Mechanistic experiments revealed that the OA nonamers effectively target the influenza HA protein. This study demonstrates the effectiveness of a multivalent structure-activity binding strategy for designing influenza virus inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Yanmei Luo, Jin Li, Yuliang Zong, Mengxin Sun, Wan Zheng, Jiapeng Zhu, Liu Liu, Bing Liu
Summary: This study identifies a potent SHP2 allosteric inhibitor and provides insights into its structure-activity relationship through comparison of co-crystal structures. These results have implications for understanding the mode of action and designing other allosteric inhibitors of SHP2.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Xiuxiu Ma, Meng Wang, Fan Wang, Jiao Li, Zhengguang Zhang, Jiapeng Zhu, Bing Liu
Summary: In this study, a small-molecule BRD4 inhibitor named compound 3 was identified as an effective inhibitor of BRD4 activity. Co-crystal structure analysis revealed that compound 3 occupies the KAc recognition pockets of BRD4 by forming key hydrogen bonds with Asn140 and engaging in hydrophobic interactions, thereby hindering the binding of acetylated lysine to BRD4. These findings suggest that compound 3 can serve as a lead compound for the development of structurally novel BRD4 inhibitors.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Multidisciplinary Sciences
Gonzalo L. Gonzalez-Del Pino, Kunhua Li, Eunyoung Park, Anna M. Schmoker, Byung Hak Ha, Michael J. Eck
Summary: The dysregulation of the RAF/MEK/ERK pathway is associated with many cancers, making the proteins involved, like MEK, a focus of drug discovery efforts. Allosteric MEK inhibitors have complex effects on this pathway and are used in combination with BRAF inhibitors in malignant melanoma. Recent studies suggest that these inhibitors act most potently on BRAF/MEK complexes rather than on free active MEK.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Microbiology
Kin Kui Lai, James B. B. Munro, Guoli Shi, Saliha Majdoul, Alex A. A. Compton, Alan Rein
Summary: Serine incorporator 5 (Ser5) is a host antiviral factor against HIV-1, gammaretroviruses, and Influenza A virus (IAV). It inhibits virus-cell fusion by interacting with HA proteins and destabilizing the pre-fusion conformation of IAV HA. This study provides insights into the antiviral mechanism of Ser5.
Article
Chemistry, Multidisciplinary
Guillermo Moreno-Pescador, Mohammad Reza Arastoo, Victoria Thusgaard Ruhoff, Salvatore Chiantia, Robert Daniels, Poul Martin Bendix
Summary: Many cellular processes involve the lateral organization of membrane proteins into nanoscale domains. The mechanisms behind the clustering of membrane proteins into nanoscale lipid domains are not well understood. In this study, a method combining optical trapping, thermo-plasmonic-mediated membrane fusion, and confocal imaging was developed to investigate the phase affinity of membrane proteins. It was observed that the transferred membrane proteins partitioned into the liquid disordered phase of the model membranes. This generic platform allows the study of phase affinity for any plasma membrane protein labeled with a fluorescent marker.