Article
Pharmacology & Pharmacy
Ling Ma, Quanjie Li, Yongli Xie, Jianyuan Zhao, Dongrong Yi, Saisai Guo, Fei Guo, Jing Wang, Long Yang, Shan Cen
Summary: In this study, a cell-based assay for screening inhibitors against SARS-CoV-2 3CLpro was established using bioluminescence resonance energy transfer (BRET) technology. The assay was applied to screen a collection of known HIV/HCV protease inhibitors, and it was found that simeprevir showed the most potency against 3CLpro with the ability to bind to its active site pocket. This research demonstrates the feasibility of using the cell-based BRET assay for screening 3CLpro inhibitors and supports the potential of simeprevir for the development of such inhibitors.
ANTIVIRAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen, Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon, Pieter Leyssen
Summary: This study reports the results of a phenotypic screening campaign in an EU-funded project, identifying 110 compounds with anti-cytopathic capabilities, including 18 marketed drugs suitable for potential therapies against COVID-19.
Article
Biochemistry & Molecular Biology
Ling Ma, Yongli Xie, Mei Zhu, Dongrong Yi, Jianyuan Zhao, Saisai Guo, Yongxin Zhang, Jing Wang, Quanjie Li, Yucheng Wang, Shan Cen
Summary: In this study, Darunavir derivatives that inhibit SARS-CoV-2 3CL(pro) were identified through a high-throughput screening method. These compounds showed favorable antiviral activity and similar potency against Omicron variants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Bruno Rizzuti, Laura Ceballos-Laita, David Ortega-Alarcon, Ana Jimenez-Alesanco, Sonia Vega, Fedora Grande, Filomena Conforti, Olga Abian, Adrian Velazquez-Campoy
Summary: Research has found that the natural compound eugenol can effectively inhibit the enzymatic activity of the main protease 3CLpro of SARS-CoV-2, with a low inhibition constant. Two other analogs also have an impact, but to a lesser extent. These compounds are capable of inhibiting the activity of the virus main protease in vitro.
Article
Biochemistry & Molecular Biology
Kazuhiro Sugamoto, Yuri L. Tanaka, Akatsuki Saito, Yoh Goto, Takayuki Nakayama, Tamaki Okabayashi, Hisato Kunitake, Kazuhiro Morishita
Summary: The study reveals that the proanthocyanidin (PAC) fraction in blueberry leaves has strong antiviral activity against HCV and HTLV-1, and the BB-PAC derived from Kunisato 35 Gou blueberry inhibits SARS-CoV-2 infection regardless of the time of infection.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Yash Gupta, Dawid Maciorowski, Samantha E. Zak, Krysten A. Jones, Rahul S. Kathayat, Saara-Anne Azizi, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Andrew S. Herbert, Ajay Bharti, Brijesh Rathi, Ravi Durvasula, Daniel P. Becker, Bryan C. Dickinson, John M. Dye, Prakasha Kempaiah
Summary: This study focused on the repurposing of approved and investigational drugs/compounds for SARS-CoV-2, utilizing virtual screening to identify potential inhibitors against the virus. The top eight candidates were further validated through molecular dynamics simulation and in-vitro experiments, with Bisindolylmaleimide IX (BIM IX) showing significant antiviral activity and validating the pipeline used in this study.
Article
Chemistry, Medicinal
Arun K. Ghosh, Jakka Raghavaiah, Dana Shahabi, Monika Yadav, Brandon J. Anson, Emma K. Lendy, Shin-ichiro Hattori, Nobuyo Higashi-Kuwata, Hiroaki Mitsuya, Andrew D. Mesecar
Summary: This study investigated the synthesis, structure-activity relationship, enzyme inhibition, antiviral activity, and X-ray crystallographic studies of 5-chloropyridinyl indole carboxylate derivatives as potent SARS-CoV-2 chymotrypsin-like protease inhibitors. Compound 1 demonstrated strong inhibitory and antiviral activity, comparable to Remdesivir. Compound 7d showed the most potent enzyme inhibitory activity. X-ray crystal structures of compounds 2, 7b, and 9d bound to SARS-CoV 3CLpro were determined to provide molecular insight into their binding properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Food Science & Technology
Carla Guijarro-Real, Mariola Plazas, Adrian Rodriguez-Burruezo, Jaime Prohens, Ana Fita
Summary: Research has identified plant extracts and molecules as potential treatments for COVID-19, laying the groundwork for future chemical, in vivo, and clinical trials.
Article
Biochemical Research Methods
Shaokang Ren, Keith Fraser, Lili Kuo, Neha Chauhan, Addison T. Adrian, Fuming Zhang, Robert J. Linhardt, Paul S. Kwon, Xing Wang
Summary: Researchers have designed DNA nanostructures that can bind to viral antigens and effectively inhibit dengue virus infection. By using existing structural data and various experimental methods, these DNA nanostructures can be synthesized, characterized, and evaluated for their antiviral efficacy.
Article
Biochemistry & Molecular Biology
Elena N. Esimbekova, Valeriya P. Kalyabina, Kseniya V. Kopylova, Victoria I. Lonshakova-Mukina, Anna A. Antashkevich, Irina G. Torgashina, Kirill A. Lukyanenko, Elena V. Nemtseva, Valentina A. Kratasyuk
Summary: Pesticides can adversely affect both individual organisms and the entire ecosystem. This study used an enzyme inhibition-based assay to examine the molecular-level effects of pesticides. The study found that pesticide formulations have a stronger inhibitory effect on enzyme activity and bioluminescence than the active ingredients alone, highlighting the contribution of formulants to the toxicological properties of pesticides. Additionally, the study revealed that inert ingredients in pesticide formulations can significantly enhance their inhibitory effects, suggesting the need for stricter control over their use.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Aarthy Murali, Sushil Kumar, Srinivasan Akshaya, Sanjeev K. K. Singh
Summary: This study investigates the binding sites of four flaviviral RdRp and provides insights into various molecular interactions using a computational approach. The research helps identify potent compounds that can inhibit viral proteins as common inhibitors and proposes possible mechanisms of inhibition through conformational stability analysis.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Chemistry, Physical
Xueying Luo, Xiaowei Wang, Yuan Yao, Xin Gao, Lu Zhang
Summary: This study has elucidated the template-dependent inhibitory mechanism of remdesivir on SARS-CoV-2 RdRp and identified the molecular mechanism of drug resistance caused by the V557L mutation.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Immunology
Marie-Clotilde Bernard, Joanna Waldock, Sylvie Commandeur, Lea Strauss, Claudia Maria Trombetta, Serena Marchi, Fan Zhou, Serge van de Witte, Peter van Amsterdam, Sammy Ho, Katja Hoschler, Vladimir Lugovtsev, Jerry P. Weir, Emanuele Montomoli, Rebecca J. Cox, Othmar G. Engelhardt, Damien Friel, Ralf Wagner, Thierry Ollinger, Sophie Germain, Hanna Sediri-Schoen
Summary: This study validated a harmonized assay for quantifying anti-NA antibodies in influenza. The assay demonstrated precision, specificity, and robustness in testing influenza vaccines. Additionally, the use of a calibrator significantly improved inter-laboratory agreement.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Senbiao Fang, Chuqi Lei, Meng Li, Yongfan Ming, Liren Liu, Xuming Zhou, Min Li
Summary: Studying the mutational characterization of 2019-nCoV-Spike protein is crucial for the development of effective drugs and new vaccines.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Xiaoting Liu, Caijing Han, Li Fang, Zhanqing Fan, Yanan Wang, Xin Gao, Junhua Shi, Weihong Min
Summary: The study successfully increased enzyme activity by mutating key allosteric regulatory sites. Molecular dynamics simulations revealed that Lys inhibits enzymatic reaction by affecting protein conformation.
Article
Biochemistry & Molecular Biology
Hebah Fatafta, Batuhan Kav, Bastian F. Bundschuh, Jennifer Loschwitz, Birgit Strodel
Summary: There is increasing evidence linking Alzheimer's disease progression and severity to neuronal membrane damage caused by aggregates of the amyloid-β (Aβ) peptide. The lipid-chaperone hypothesis suggests that complexes between Aβ and free lipids allow for easy insertion into membranes. However, experiments show that 1:1 complexes do not insert into membranes but rather adsorb to the membrane surface, with significant structural changes occurring when Aβ forms a complex with a cluster of lipid molecules.
BIOPHYSICAL CHEMISTRY
(2022)
Review
Virology
Rafaela dos S. Peinado, Raphael J. Eberle, Carolina C. Pacca, Raghuvir K. Arni, Monika A. Coronado
Summary: This article discusses arboviruses, which are transmitted to vertebrate hosts by arthropods, primarily mosquitoes. These viruses, such as Dengue, Zika, Saint Louis Encephalitis, and others, are associated with various neurological, viscerotropic, and hemorrhagic diseases. Researchers have used a variety of methods, including genomics and proteomics, to study the structures of these viruses and their interactions with hosts, which is crucial for the development of future antiviral therapies.
Article
Biochemistry & Molecular Biology
Jorge E. Hernandez Gonzalez, Raphael J. Eberle, Dieter Willbold, Monika A. Coronado
Summary: This study identified D-peptides as potential drug candidates against SARS-CoV-2 main protease through structure-based virtual screening and in vitro enzymatic assays, presenting a promising computational strategy for identifying D-peptides capable of inhibiting the protease.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Maryam O. Olagunju, Jennifer Loschwitz, Olujide O. Olubiyi, Birgit Strodel
Summary: Sickle cell disease is caused by a protein mutation leading to pathological aggregation, which can be studied through multiscale molecular dynamics simulations to understand the aggregation mechanism for the development of potential treatments.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2022)
Article
Chemistry, Medicinal
Raphael J. Eberle, Ian Gering, Markus Tusche, Philipp N. Ostermann, Lisa Muller, Ortwin Adams, Heiner Schaal, Danilo S. Olivier, Marcos S. Amaral, Raghuvir K. Arni, Dieter Willbold, Monika A. Coronado
Summary: The C30 endopeptidase is crucial for the life cycle of SARS-CoV-2 and is a potential drug target. Crotamine, a peptide isolated from rattlesnake venom, has shown promising activities and derivatives such as L-peptides have exhibited inhibitory effects on 3CL protease. D-peptides have shown potential as a prototype for peptide-based drugs targeting viral protease 3CL(pro).
Article
Chemistry, Physical
Lara Pfaff, Jian Gao, Zhishuai Li, Anna Jaeckering, Gert Weber, Jan Mican, Yinping Chen, Weiliang Dong, Xu Han, Christian G. Feiler, Yu-Fei Ao, Christoffel P. S. Badenhorst, David Bednar, Gottfried J. Palm, Michael Lammers, Jiri Damborsky, Birgit Strodel, Weidong Liu, Uwe T. Bornscheuer, Ren Wei
Summary: Thermophilic polyester hydrolases (PES-H) play a crucial role in the biocatalytic recycling of synthetic polyester polyethylene terephthalate (PET). By studying the crystal structures of two enzymes derived from metagenomes, researchers gained insights into the mechanism of enzymatic PET hydrolysis. Mutations in key residues resulted in improved hydrolytic activity of certain variants, making them potential candidates for industrial plastic recycling processes.
Article
Microbiology
Raphael J. Eberle, Danilo S. Olivier, Marcos S. Amaral, Carolina C. Pacca, Mauricio L. Nogueira, Raghuvir K. Arni, Dieter Willbold, Monika A. Coronado
Summary: This study demonstrates the inhibitory potential of the water-soluble vitamin riboflavin against NS2B/NS3(pro) of ZIKV and YFV and nsP2(pro) of CHIKV, and its ability to inhibit the viral entry of CHIKV. Molecular dynamics simulations validate the repurposing of riboflavin as a promising molecule in drug development against these viruses.
Editorial Material
Biochemistry & Molecular Biology
Catherine Musselman, Voula Kanelis, Sophie Lecomte, Birgit Strodel
BIOPHYSICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Moritz Schaeffler, Mohammed Khaled, Birgit Strodel
Summary: The structural heterogeneity and dynamics of intrinsically disordered proteins (IDPs) present a challenge for their characterization solely by experimental techniques. Molecular dynamics simulations offer a powerful complement to experimental approaches. In this study, the construction of transition networks from MD trajectories is demonstrated as a means to reveal the configurational ensemble and structural interconversions of IDPs, using amyloid-beta peptide as an example.
Review
Virology
Rafaela dos S. Peinado, Raphael J. Eberle, Raghuvir K. Arni, Monika A. Coronado
Summary: This article reviews the omics studies on mosquito-borne viruses and highlights the importance of multi-omics approaches in understanding the pathogenesis and host-viral interactions of these viruses. It suggests that these studies can offer new perspectives for developing antiviral drugs or therapies.
Article
Biochemistry & Molecular Biology
Oliver H. Weiergraeber, Dusan Petrovic, Andreas Kislat, Martin Pattky, Judith Fabig, Renu Batra-Safferling, Jan Schulte Am Esch, Karen Haenel, Carolin Huhn, Birgit Strodel, Bernhard Homey, Dieter Willbold
Summary: CCL16 is primarily synthesized by hepatocytes, circulates in the blood as a full-length protein, and the C-terminal extension may impair its biological activity modulation.
Article
Biochemistry & Molecular Biology
Raphael J. Eberle, Marc Sevenich, Ian Gering, Lara Scharbert, Birgit Strodel, Nils A. . Lakomek, Karoline Santur, Jeannine Mohrlueder, Monika A. . Coronado, Dieter Willbold
Summary: A novel and efficient next-generation sequencing (NGS) supported phage display selection strategy was used to identify a set of peptide ligands that inhibit the SARS-CoV-2 3CL protease. These ligands have the potential to be lead compounds for therapeutic development and address limitations associated with current L-peptide inhibitors.
ACS CHEMICAL BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Monika A. Coronado, Ian Gering, Marc Sevenich, Danilo S. Olivier, Mohammadamin Mastalipour, Marcos S. Amaral, Dieter Willbold, Raphael J. Eberle
Summary: Epigallocatechin molecules, found in green tea, have shown great potential in inhibiting flaviviruses such as Dengue, yellow fever, West Nile, and Zika. This discovery could lead to the development of more effective antiviral drugs.
Article
Chemistry, Multidisciplinary
Batuhan Kav, Birgit Strodel
Summary: Simulating the amyloid aggregation process with atomic detail is challenging due to the difficulty in parametrizing a force field that accurately represents all protein states. In this study, the consideration of electronic polarizability was tested to improve the description of different states of A beta(16-22). Surprisingly, the CHARMM Drude polarizable force field performed worse than its unpolarizable counterpart CHARMM36m. The sources for this failure of the Drude model are discussed.
Correction
Biochemistry & Molecular Biology
Mohamed Marzouk, Shimaa M. Khalifa, Amal H. Ahmed, Ahmed M. Metwaly, Hala Sh. Mohammed, Hanan A. A. Taie
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Gerardo Andres Libreros-Zuniga, Danilo Pava e Pavao, Vinicius de Morais Barroso, Nathalya Cristina de Moraes Roso Mesquita, Saulo Fehelberg Pinto Braga, Glaucius Oliva, Rafaela Salgado Ferreira, Kelly Ishida, Marcio Vinicius Bertacine Dias
Summary: Tuberculosis is a major global cause of death, and the emergence of drug-resistant strains has increased the burden of this disease. New alternative therapies are constantly needed, and recent research has identified small molecules as potential inhibitors of Ldts in M. tuberculosis, which have antimycobacterial activity.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Xiao-Dong Wang, Yong-Si Liu, Ming-Hao Hu
Summary: In this study, a selffolded fluorescent probe was designed to selectively illuminate G4s by unfolding its intramolecular aggregation mediated by G4 binding. This probe showed more controllable background emission and promising ability to track G4 forming dynamics compared to previous disaggregation-induced emission (DIE) probes.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yu Xiang, Zhuo Yuan, Qichuan Deng, Linshen Xie, Dongke Yu, Jianyou Shi
Summary: This review provides a brief description of the diagnosis, pathogenesis, and potential therapeutic inhibitors for renal fibrosis. Currently, there are no clear therapeutic targets or drugs for renal fibrosis; however, some natural products may have potential efficacy for treating renal fibrosis.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Simone Giovannuzzi, Anna Nikitjuka, Bruna Rafaela Pereira Resende, Michael Smietana, Alessio Nocentini, Claudiu T. Supuran, Jean-Yves Winum
Summary: Boron-based compounds have been extensively studied in medicinal chemistry, playing a crucial role in designing small molecule drugs for various diseases. Boron is particularly valuable in developing inhibitors for metalloenzymes carbonic anhydrases, and it can modulate ligand recognition ability and selectivity. Recent advancements have led to the discovery of novel boron-based inhibitors that can inhibit carbonic anhydrases through a Lewis acid-base mechanism. Further research is needed to fully explore the potential of boron-based inhibitors and advance their clinical applications.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Xinxin Liu, Lei Chen, Ze Chen
Summary: This study developed a nanostructured photosensitizer loaded with oxygen-throttling drug and demonstrated its enhanced cytotoxicity against tumor cells under hypoxic conditions. Animal experiments showed the enhanced tumor targeting capability of the photosensitizer and its inhibitory effect on tumor growth.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Shuai Jiang, Wen-Yan Li, Zai-Feng Yuan, Qin-Shi Zhao
Summary: This study isolated two new dimeric Lycopodium alkaloids and twelve previously undescribed Lycopodium alkaloids from Lycopodiastrum casuarinoides. The structures of these compounds were determined and their inhibitory activities on the Cav3.1 channel were evaluated.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yan Yang, Dong-Xiao Yan, Rui-Xue Rong, Bing-Ye Shi, Man Zhang, Jing Liu, Jie Xin, Tao Xu, Wen-Jie Ma, Xiao-Liu Li, Ke-Rang Wang
Summary: In this study, a series of nucleolar fluorescent probes based on naphthalimide derivatives were designed and synthesized, which could achieve clear nucleolar staining in living cells. The results showed that these probes exhibited good targeting to the cell nucleolus and could bind to RNA and enhance fluorescence. This has positive implications for the diagnosis and treatment of nucleolus-related diseases.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yongxi Dong, Fang Wang, Jinlan Wen, Yongqing Mao, Shanhui Zhang, Tiemei Long, Zhangxiang Yang, Lei Li, Jiquan Zhang, Li Dong, Gang Liu, Jianwei Xu
Summary: The hybrid molecules of Scutellarein and Tertramethylpyrazine show excellent neuroprotective and antiplatelet effects in the treatment of ischemic stroke. Compound 1e is particularly effective, enhancing cell membrane permeability and inhibiting cell uptake, as well as significantly reducing cerebral infarction volume.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yu Chen, Yuanyuan Ying, Jonathan Lalsiamthara, Yuheng Zhao, Saber Imani, Xin Li, Sijing Liu, Qingjing Wang
Summary: This paper examines the role and metabolic regulation of NAD+ in bacteria, highlighting its impact on physiology and virulence. It explores enzymes associated with NAD+ metabolism as potential targets for antibacterial drugs and vaccine candidates. Additionally, it scrutinizes the medical potential of NAD+ and provides insights for its application in biomedicine.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Jon Macicior, Daniel Fernandez, Silvia Ortega-Gutierrez
Summary: Hutchinson-Gilford progeria syndrome (HGPS), also known as progeria, is a rare genetic disease that causes premature aging and significantly reduces life expectancy. Currently, there is only one approved drug for treating progeria, but its efficacy is limited. Progerin levels are believed to be the most important biomarker related to disease severity.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Fuko Hirano, Naoya Kondo, Yusuke Murata, Aya Sudani, Takashi Temma
Summary: Fluorinated alpha-methyl 3BPA derivatives showed improved water solubility, tumor targetability, and biodistribution compared to 3BPA and BPA, resulting in significantly improved tumor-to-normal tissue ratios.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Ying Shi, Jiaqin Tang, Shumeng Zhi, Ruiqi Jiang, Qing Huang, Lei Sun, Zhizhong Wang, Yanran Wu
Summary: Necroptosis is a type of cell death associated with various diseases. In this study, we identified a small molecule inhibitor, SY-1, that effectively blocks necroptosis by inhibiting the phosphorylation of RIP1/RIP3/MLKL pathway. SY-1 also showed protective effects against TNF-induced hypothermia and improved survival in mice with SIRS. These findings highlight the potential therapeutic applications of SY-1.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Andrea Bagan, Sonia Abas, Judith Pala-Pujadas, Alba Irisarri, Christian Grinan-Ferre, Merce Pallas, Itziar Muneta-Arrate, Carolina Muguruza, Luis F. Callado, Belen Perez, Elies Molins, Jose A. Morales-Garcia, Carmen Escolano
Summary: Recent studies have identified the modulation of imidazoline I-2 receptors (I-2-IR) by selective ligands as a potential strategy for treating neurodegenerative diseases. This study reports a family of bicyclic alpha-iminophosphonates that show high affinity and selectivity for I-2-IR and demonstrates their neuroprotective and anti-inflammatory effects in in vitro and in vivo models. The findings emphasize the importance of exploring structurally novel I-2-IR ligands for therapeutic strategies in neurodegeneration.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Qiuping Xiang, Tianbang Wu, Cheng Zhang, Chao Wang, Hongrui Xu, Qingqing Hu, Jiankang Hu, Guolong Luo, Xiaoxi Zhuang, Xishan Wu, Yan Zhang, Yong Xu
Summary: This study reports the discovery of a 1-(indolizin-3-yl)ethan-1-one derivative as a potent and selective CBP bromodomain inhibitor for AML drug development.
BIOORGANIC CHEMISTRY
(2024)