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
Biochemistry & Molecular Biology
Tao Wang, Jinhua Wu, Wei Dong, Mengwen Wang, Xiaodan Zhong, Wenjun Zhang, Lei Dai, Yang Xie, Yujian Liu, Xingwei He, Wanjun Liu, Thati Madhusudhan, Hesong Zeng, Hongjie Wang
Summary: This study identifies the previously unknown function of the MEK/ERK pathway in regulating ER stress in diabetic cardiomyopathy. MEK inhibition with U0126 can ameliorate diabetic cardiomyopathy by regulating the IRE1 alpha-XBP1s pathway and promoting XBP1s' nuclear accumulation, indicating a potential therapeutic target for DCM.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Immunology
Helen Hoffmann, Marina Ebensperger, Annika Schoensiegel, Hazem Hamza, Julia Koch-Heier, Andre Schreiber, Stephan Ludwig, Michael Schindler, Oliver Planz
Summary: The urgent need for broad-spectrum antivirals has been highlighted by the COVID-19 pandemic. In this study, the antiviral efficacy of zapnometinib was compared between influenza A virus (IAV) and SARS-CoV-2, revealing that IAV is more susceptible to treatment with zapnometinib compared to SARS-CoV-2.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Immunology
Huan Cui, Cheng Zhang, Chunmao Zhang, Zhuming Cai, Ligong Chen, Zhaoliang Chen, Kui Zhao, Sina Qiao, Yingchun Wang, Lijia Meng, Shishan Dong, Juxiang Liu, Zhendong Guo
Summary: Lentinan has been shown to have a high degree of protection against influenza virus in the ICR mouse model, making it a potential new anti-influenza drug. Its mechanisms include inhibiting the inflammatory response and reducing cytokine storms caused by influenza virus infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Virology
Stephan Ludwig, Stephan Pleschka, Oliver Planz
Summary: Acute hyperinflammatory virus infections, such as influenza or coronavirus disease-19, are still a major health burden worldwide. Direct-acting antivirals may induce viral resistance, while a host-targeted strategy using inhibitors of the cellular Raf/MEK/ERK kinase cascade shows potential in blocking virus replication and suppressing cytokine response. The MEK inhibitor Zapnometinib has shown evidence of clinical benefit in a phase-II clinical trial.
CURRENT OPINION IN VIROLOGY
(2023)
Article
Chemistry, Medicinal
Hui-Xian Wang, Mao-Sen Zeng, Yi Ye, Jin-Yuan Liu, Pei-Ping Xu
Summary: Puerarin, a major isoflavone compound from Pueraria lobata root, exhibits various properties including anti-inflammatory, antioxidant, and antiviral effects. It shows inhibitory activity against H1N1 influenza virus by blocking viral NP transport and newly formed virus particle release. In vivo studies demonstrate its potential as a treatment for influenza virus infection, with effective antiviral activity and reduced inflammation in the lungs.
PHYTOTHERAPY RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Jeremy C. Jones, Hui-Ling Yen, Peter Adams, Kimberly Armstrong, Elena A. Govorkova
Summary: Effective antivirals play a crucial role in the early phase of an influenza pandemic, before vaccines are available. Currently, two classes of antiviral drugs are approved for influenza treatment, but resistance has been observed. Therefore, it is important to develop novel antiviral options that target both the virus and the host. This review explores the drawbacks of current antivirals and ongoing research on new agents or combination therapies to address these limitations.
ANTIVIRAL RESEARCH
(2023)
Article
Immunology
Minjin Kim, Yucheol Cheong, Jinhee Lee, Jongkwan Lim, Sanguine Byun, Yo Han Jang, Baik Lin Seong
Summary: This study demonstrated that caspase-triggered live attenuated influenza vaccine induced broad reactive antibody response and provided heterosubtypic protection against diverse influenza viruses in mice model. The protection relied on non-neutralizing antibodies-mediated ADCC activities and robust mucosal secretion of sIgA, which highlight the potential of this vaccine as a promising option for developing a universal influenza vaccine.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Avishak Sarker, Zichen Gu, Lu Mao, Yongzhuang Ge, Duoduo Hou, Jieyu Fang, Zhanyong Wei, Zhenya Wang
Summary: Influenza is a century-old disease that poses challenges to humans due to its mutating nature, seasonal epidemics, and occasional pandemics. The limited effectiveness of strain-specific vaccines and the growing drug resistance to anti-influenza drugs call for the development of novel drugs with broad reactivity, higher bioavailability, easier administration, and fewer side effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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.
Review
Medicine, General & Internal
Timothy M. Uyeki, David S. Hui, Maria Zambon, David E. Wentworth, Arnold S. Monto
Summary: Seasonal influenza caused by influenza A and B viruses is a significant global burden. Vaccination is the primary prevention measure, but novel influenza viruses still pose pandemic threats.
Review
Biochemistry & Molecular Biology
Hyeon Jin Kim, Mi Suk Jeong, Se Bok Jang
Summary: The influenza virus causes significant human morbidity and mortality worldwide. Developing new anti-influenza drugs is urgently needed, with small molecules targeting NS1 being identified as a potential pathway for drug development. NS1 plays a crucial role in host antiviral responses, making it a key target for new therapeutic interventions against the virus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
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
Virology
Emi Takashita, Shin Murakami, Yoko Matsuzaki, Seiichiro Fujisaki, Hiroko Morita, Shiho Nagata, Misa Katayama, Katsumi Mizuta, Hidekazu Nishimura, Shinji Watanabe, Taisuke Horimoto, Hideki Hasegawa
Summary: To minimize public health risks, monitoring antiviral susceptibilities of influenza viruses is crucial. This study tested the susceptibility of influenza C and D viruses to RNA polymerase inhibitors and found that all tested viruses were susceptible without any associated amino acid substitutions. The combined use of focus reduction assay and genotypic assay has proven valuable for monitoring antiviral susceptibilities of influenza C and D viruses.
Article
Public, Environmental & Occupational Health
Christian Boeing, Christian Sandten, Eike R. Hrincius, Darisuren Anhlan, Andreas Dworog, Stephanie Hanning, Thilo Kuennemann, Christopher Niehues, Thomas Schupp, Edyta Stec, Julius Thume, Daniel Triphaus, Markus Wilkens, Holger Uphoff, Josef Zuendorf, Anja Jacobshagen, Martin Kreyenschmidt, Stephan Ludwig, Hans-Christoph Mertins, Alexander Mellmann
Summary: This study aimed to develop a simple, inexpensive, and ecological method for decontamination of disposable FFPs while preserving filtration efficiency and material integrity. The results showed that immersion in a 6% acetic acid and 6% hydrogen peroxide solution for 30 minutes completely eliminated contaminants without compromising the performance of FFPs.
AMERICAN JOURNAL OF INFECTION CONTROL
(2022)
Article
Biotechnology & Applied Microbiology
Viktor Wixler, Igor Z. Zaytsev, Rafael Leite Dantas, Tanja Schied, Yvonne Boergeling, Veronika Luehrmann, Georg Varga, Doerthe Masemann, Stephan Ludwig
Summary: The restoration of immune tolerance is crucial in treating autoimmune diseases. Small splenic peptides (SSPs) have been found to convert dendritic cells (DCs) into tolerogenic cells, leading to the differentiation of naive CD4+ cells into Foxp3-expressing T regulatory cells (Tregs), and effectively suppressing the development of psoriatic arthritis.
Article
Immunology
Yeonsu Kim, Xiaoyan Zheng, Kathrin Eschke, M. Zeeshan Chaudhry, Federico Bertoglio, Adriana Tomic, Astrid Krmpotic, Markus Hoffmann, Yotam Bar-On, Julia Boehme, Dunja Bruder, Thomas Ebensen, Linda Brunotte, Stephan Ludwig, Martin Messerle, Carlos Guzman, Ofer Mandelboim, Michael Hust, Stefan Poehlmann, Stipan Jonjic, Luka Cicin-Sain
Summary: CMV vectors induce long-term cellular immunity and long-term immune protection against clinically relevant respiratory pathogens.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Jonas Schuhenn, Toni Luise Meister, Daniel Todt, Thilo Bracht, Karin Schork, Jean-Noel Billaud, Carina Elsner, Natalie Heinen, Zehra Karakoese, Sibylle Haid, Sriram Kumar, Linda Brunotte, Martin Eisenacher, Yunyun Di, Jocelyne Lew, Darryl Falzarano, Jieliang Chen, Zhenghong Yuan, Thomas Pietschmann, Bettina Wiegmann, Hendrik Uebner, Christian Taube, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Adalbert Krawczyk, Stephan Ludwig, Barbara Sitek, Eike Steinmann, Ulf Dittmer, Kerry J. Lavender, Kathrin Sutter, Stephanie Pfaender
Summary: This study found that different subtypes of IFN-alpha have varying antiviral activity against SARS-CoV-2, with IFN-alpha 5 showing the highest efficacy. Combination treatment with the broad antiviral drug remdesivir enhanced the antiviral effect. These findings are important for understanding the mechanism of IFN-I-mediated antiviral response and developing treatments for COVID-19.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Aaqib Sohail, Azeem A. Iqbal, Nishika Sahini, Fangfang Chen, Mohamed Tantawy, Syed F. H. Waqas, Moritz Winterhoff, Thomas Ebensen, Kristin Schultz, Robert Geffers, Klaus Schughart, Matthias Preusse, Mahmoud Shehata, Heike Baehre, Marina C. Pils, Carlos A. Guzman, Ahmed Mostafa, Stephan Pleschka, Christine Falk, Alessandro Michelucci, Frank Pessler
Summary: Excessive inflammation caused by viral infections, including influenza, can lead to severe illness and death. Itaconate, a metabolite that modulates the immune response, has been found to have antiviral effects and can redirect inflammatory responses. In this study, researchers investigated the effects of itaconate and its variants on the host's response to influenza A virus. They found that treatment with itaconate and its variants reduced viral replication and inflammation in both mice and human cells. The compounds also modulated interferon responses and reduced the release of pro-inflammatory chemokines. Overall, these findings suggest that itaconates could be used as immunomodulatory and antiviral interventions for influenza virus infection.
Article
Virology
Wiebke Obermann, Alexandra Friedrich, Ramakanth Madhugiri, Paul Klemm, Jan Philipp Mengel, Torsten Hain, Stephan Pleschka, Hans-Guido Wendel, Roland K. Hartmann, Susanne Schiffmann, John Ziebuhr, Christin Mueller, Arnold Gruenweller
Summary: Rocaglates are a class of broad-spectrum antiviral compounds that inhibit viral protein synthesis for different RNA viruses. They have differences in cytotoxicity against human immune cells, RNA-clamping efficiency, and antiviral activity. The results suggest that they have the potential to be effective antiviral drugs and are unlikely to lead to the emergence of viral escape mutations.
Article
Cell & Tissue Engineering
Yotam Menuchin-Lasowski, Andre Schreiber, Aaron Lecanda, Angeles Mecate-Zambrano, Linda Brunotte, Olympia E. Psathaki, Stephan Ludwig, Thomas Rauen, Hans R. Schoeler
Summary: Several studies have shown that SARS-CoV-2 can infect and replicate in retinal cells, inducing inflammatory responses and relying on ACE2 for infection. Therefore, it is important to monitor the potential effects of COVID-19 on the retina.
Article
Respiratory System
Katja Hoenzke, Benedikt Obermayer, Christin Mache, Diana Fathykova, Mirjana Kessler, Simon Doekel, Emanuel Wyler, Morris Baumgardt, Anna Loewa, Karen Hoffmann, Patrick Graff, Jessica Schulze, Maren Mieth, Katharina Hellwig, Zeynep Demir, Barbara Biere, Linda Brunotte, Angeles Mecate-Zambrano, Judith Bushe, Melanie Dohmen, Christian Hinze, Sefer Elezkurtaj, Mario Toennies, Torsten T. Bauer, Stephan Eggeling, Hong-Linh Tran, Paul Schneider, Jens Neudecker, Jens C. Rueckert, Kai M. Schmidt-Ott, Jonas Busch, Frederick Klauschen, David Horst, Helena Radbruch, Josefine Radke, Frank Heppner, Victor M. Corman, Daniela Niemeyer, Marcel A. Mueller, Christine Goffinet, Ronja Mothes, Anna Pascual-Reguant, Anja Erika Hauser, Dieter Beule, Markus Landthaler, Stephan Ludwig, Norbert Suttorp, Martin Witzenrath, Achim D. Gruber, Christian Drosten, Leif-Erik Sander, Thorsten Wolff, Stefan Hippenstiel, Andreas C. Hocke
Summary: This study reveals that severe lung injury in COVID-19 may result from macrophage-triggered immune activation rather than direct viral damage to the alveolar compartment.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Review
Cell Biology
Aileen Faist, Josua Janowski, Sriram Kumar, Saskia Hinse, Duygu Merve Caliskan, Julius Lange, Stephan Ludwig, Linda Brunotte
Summary: Respiratory infections with newly emerging zoonotic viruses can cause severe disease and high mortality by perturbing the human immune responses. This review discusses the similarities and differences between SARS-CoV-2 and highly pathogenic avian influenza viruses in terms of immune induction, disease dynamics, and long-term sequelae. It also highlights important lessons about the effectiveness of antiviral and immunomodulatory therapeutic strategies learned from this pandemic.
Article
Immunology
Sebastian Schloer, Daniel Treuherz, Aileen Faist, Marlous de Witt, Katharina Wunderlich, Rainer Wiewrodt, Karsten Wiebe, Peter Barth, Joo-Hee Waelzlein, Susann Kummer, Anne Balkema-Buschmann, Stephan Ludwig, Linda Brunotte, Ursula Rescher
Summary: In order to study the viral life cycle, describe the pathophysiological consequences of viral infection, and explore possible drug targets and treatment options, it is necessary to establish physiologically relevant models. This study established a murine lung tissue explant platform for studying influenza A virus and SARS-CoV-2. The platform demonstrated efficient viral replication, release of inflammatory cytokines, and induction of antiviral interferon response.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Pharmacology & Pharmacy
Andre Schreiber, Benjamin Ambrosy, Oliver Planz, Sebastian Schloer, Ursula Rescher, Stephan Ludwig
Summary: In this study, researchers found that the MEK1/2 inhibitor ATR-002 can synergistically enhance the effect of direct-acting antivirals against SARS-CoV-2, reducing the effective concentrations of the drugs and minimizing side effects.
Article
Microbiology
Selvarani Vimalanathan, Mahmoud Shehata, Kannan Sadasivam, Serena Delbue, Maria Dolci, Elena Pariani, Sarah D'Alessandro, Stephan Pleschka
Summary: This study analyzed the inhibitory effects of Echinacea extract on various SARS-CoV-2 variants, finding that the extract has stable antiviral activity against different variants, possibly through interacting with viral proteins.
Article
Microbiology
Dayly Mashaal, Sara H. Mahmoud, Christin Mueller, Noura M. Abo Shama, Amal Abo Kamer, Ahmed A. Abdelaziz, Mohamed A. Ali, Stephan Pleschka, Ahmed Mostafa
Summary: Avian influenza virus (AIV) H9N2 is endemic in birds in the Middle East, particularly in Egypt, with multiple cases of human infections. Adaptive amino acid mutations in the viral polymerase, specifically in the PB2 gene, can enhance cross-species transmission of the virus. The presence of 591K in the PB2 gene of H9N2 strains in Egypt significantly increases the replication efficiency and polymerase activity of H5N1 variants in mammalian cells.
Article
Virology
Stephan Ludwig, Stephan Pleschka, Oliver Planz
Summary: Acute hyperinflammatory virus infections, such as influenza or coronavirus disease-19, are still a major health burden worldwide. Direct-acting antivirals may induce viral resistance, while a host-targeted strategy using inhibitors of the cellular Raf/MEK/ERK kinase cascade shows potential in blocking virus replication and suppressing cytokine response. The MEK inhibitor Zapnometinib has shown evidence of clinical benefit in a phase-II clinical trial.
CURRENT OPINION IN VIROLOGY
(2023)
Article
Cell Biology
Matthias Rohrbeck, Verena Hoerr, Ilaria Piccini, Boris Greber, Jan Sebastian Schulte, Sara-Sophie Huebner, Elena Jeworutzki, Carsten Theiss, Veronika Matschke, Joerg Stypmann, Andreas Unger, Huyen Tran Ho, Paul Disse, Nathalie Strutz-Seebohm, Cornelius Faber, Frank Ulrich Mueller, Stephan Ludwig, Ursula Rescher, Wolfgang A. A. Linke, Karin Klingel, Karin Busch, Stefan Peischard, Guiscard Seebohm
Summary: Using a transgenic mouse strain (TG) containing a CVB3 Delta VP0 genome, we have revealed virus-mediated cardiac pathophysiological processes in vivo and in vitro. Transgenic mice showed significant alterations in cardiac function, pathologic ECG alterations, calcium homeostasis, intracellular organization, and gene expression. The results also suggest that mitochondrial impairment may contribute to cardiac contractile dysfunction.