Article
Chemistry, Medicinal
Muya Xiong, Tianqing Nie, Qiang Shao, Minjun Li, Haixia Su, Yechun Xu
Summary: This study identified three potential covalent non-peptidomimetic inhibitors for the treatment of the coronavirus based on virtual screening. The effectiveness of one compound was validated through enzymatic activity assay and crystal structure analysis. The study also demonstrated an effective computational approach for seeking new covalent small molecules.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yea-In Park, Jang Hoon Kim, Siyun Lee, Ik Soo Lee, Junsoo Park
Summary: The COVID-19 pandemic has caused over six million deaths worldwide since 2019. In this study, researchers isolated eupatin from Inula japonica flowers and demonstrated its ability to inhibit coronavirus protease activity and viral replication. The results suggest that eupatin could be a potential treatment for coronavirus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Anirban Mandal, Ajeet Kumar Jha, Banasri Hazra
Summary: The ongoing COVID-19 pandemic poses a significant global health security threat with no specific treatment available. Research has shown that compounds from medicinal plants exhibit strong activity in inhibiting coronavirus 3CL protease, offering potential for the development of new drugs against COVID-19.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Lucile Brier, Haitham Hassan, Xavier Hanoulle, Valerie Landry, Danai Moschidi, Lowiese Desmarets, Yves Rouille, Julie Dumont, Adrien Herledan, Sandrine Warenghem, Catherine Piveteau, Paul Carr, Sarah Ikherbane, Francois-Xavier Cantrelle, Elian Dupre, Jean Dubuisson, Sandrine Belouzard, Florence Leroux, Benoit Deprez, Julie Charton
Summary: Since the end of 2019, the global outbreak of the coronavirus SARS-CoV-2 has caused a significant increase in infections and deaths worldwide. Researchers have identified two proteases, 3CLpro and papain-like protease, encoded by the virus that play a crucial role in the virus lifecycle. Targeting the 3CLpro, which is highly conserved within this viral family, a screening of over 89,000 small molecules led to the discovery of a potent inhibitor of the SARS-CoV-2 3CLpro. The mechanism of inhibition, interaction with the protease, specificity against host proteases, and promising antiviral properties in cells are reported.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Engineering, Environmental
Ella Borberg, Sofiya Pashko, Fernando Patolsky
Summary: This study presents an antibody-free smart pH paper-based detection platform for rapid detection of SARS-CoV-2 infection. The platform shows ultrafast detection, simplicity, cost-efficiency, and potential for multiplexed detection of other viral infections. It has implications for worldwide mass screening, particularly in remote and developing areas.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Jurica Novak, Hrvoje Rimac, Shivananda Kandagalla, Prateek Pathak, Vladislav Naumovich, Maria Grishina, Vladimir Potemkin
Summary: The study identified a more favorable allosteric binding site on the SARS-CoV-2 3CL protease, which could be a better target for non-covalent inhibitors to prevent dimerization and activation. The tyrosine kinase inhibitors radotinib and nilotinib, used for leukemia treatment, showed potential binding to this allosteric site, as confirmed by molecular dynamics simulations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Sho Kawashima, Yuki Matsui, Takumi Adachi, Yuji Morikawa, Kae Inoue, Shiori Takebayashi, Haruaki Nobori, Masatomo Rokushima, Yuki Tachibana, Teruhisa Kato
Summary: This study demonstrates that Ensitrelvir has good antiviral activity against newly emerging SARS-CoV-2 variants and globally prevalent 3CLpro mutations. Ensitrelvir shows similar inhibitory effects against Omicron variants and variants carrying 3CLpro mutations compared to the wild type.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Eunice Cho, Margarida Rosa, Ruhi Anjum, Saman Mehmood, Mariya Soban, Moniza Mujtaba, Khair Bux, Syed T. Moin, Mohammad Tanweer, Sarath Dantu, Alessandro Pandini, Junqi Yin, Heng Ma, Arvind Ramanathan, Barira Islam, Antonia S. J. S. Mey, Debsindhu Bhowmik, Shozeb Haider
Summary: This study compares the structural conservation of ligand-binding sites for M-pro enzymes from SARS-CoV2, SARS-CoV, and MERS-CoV, revealing that not all binding sites exhibit dynamic conservation despite high sequence and structural similarity. This complexity highlights the challenges of targeting all three M-pro enzymes with a single pan inhibitor.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Medicinal
Sang Hoon Han, Christopher M. Goins, Tarun Arya, Woo-Jin Shin, Joshua Maw, Alice Hooper, Dhiraj P. Sonawane, Matthew R. Porter, Breyanne E. Bannister, Rachel D. Crouch, A. Abigail Lindsey, Gabriella Lakatos, Steven R. Martinez, Joseph Alvarado, Wendell S. Akers, Nancy S. Wang, Jae U. Jung, Jonathan D. Macdonald, Shaun R. Stauffer
Summary: Starting from ML300, a structure-based optimization campaign was conducted against the SARS-CoV-2 main protease, resulting in the discovery of compound 41 with antiviral activity. This study provides important insights for the development of antiviral drugs in combating SARS-like coronavirus outbreaks.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Virology
Ah Reum Lee, Yeong Cheon Kweon, Sang Min Lee, Chan Young Park
Summary: Coronaviruses target ciliate cells and cause ciliary defects by cleaving host protein septin, leading to disoriented septin filaments, defective ciliogenesis, and inhibited Sonic Hedgehog signaling. The use of 3CL protease inhibitors can prevent abnormal ciliary structures and SHH signaling, suggesting their potential as therapeutics for treating coronaviruses-induced ciliary defects.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Medicine, General & Internal
Jonathan Daniel Ip, Allen Wing-Ho Chu, Wan-Mui Chan, Rhoda Cheuk-Ying Leung, Syed Muhammad Umer Abdullah, Yanni Sun, Kelvin Kai -Wang To
Summary: This study aimed to estimate the global prevalence of 3CLpro inhibitor-resistant SARS-CoV-2 strains. Analysis of 13.4 million sequences revealed that 0.5% of the sequences contained mutations associated with resistance to nirmatrelvir or ensitrelvir. However, resistance to 3CLpro inhibitors is currently rare.
Article
Biochemistry & Molecular Biology
Mengwei Zhu, Tiantian Fu, Mengyuan You, Junyuan Cao, Hanxi Yang, Xinyao Chen, Qiumeng Zhang, Yechun Xu, Xiangrui Jiang, Leike Zhang, Haixia Su, Yan Zhang, Jingshan Shen
Summary: A series of new peptidomimetic SARS-CoV-2 3CL protease inhibitors with unique P2 and P4 positions were synthesized and evaluated. Compound 1a and 2b exhibited significant 3CLpro inhibitory activities with IC50 values of 18.06 nM and 22.42 nM, respectively. Both 1a and 2b showed excellent in vitro antiviral activities against SARS-CoV-2, with EC50 values of 313.0 nM and 170.2 nM, respectively, which were 2- and 4-fold better than nirmatrelvir. Furthermore, these compounds demonstrated no significant cytotoxicity in vitro. Metabolic stability tests and pharmacokinetic studies revealed improved metabolic stability of 1a and 2b in liver microsomes, and 2b showed similar pharmacokinetic parameters to nirmatrelvir in mice.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Sho Iketani, Seo Jung Hong, Jenny Sheng, Farideh Bahari, Bruce Culbertson, Fereshteh Fallah Atanaki, Arjun K. Aditham, Alexander F. Kratz, Maria Luck, Ruxiao Tian, Stephen P. Goff, Hesam Montazeri, Yosef Sabo, David D. Ho, Alejandro Chavez
Summary: This study systematically investigates the mutations of SARS-CoV-2 3CL protease using a yeast-based mutational scanning approach, and validates some of the results in authentic viruses. The research reveals the high malleability of 3CL protease, while identifying immutable residues that may serve as targets for future drug inhibitors.
CELL HOST & MICROBE
(2022)
Article
Biochemistry & Molecular Biology
Seri Jo, Luca Signorile, Suwon Kim, Mi-Sun Kim, Oscar Huertas, Raul Insa, Nuria Reig, Dong Hae Shin
Summary: In this study, researchers identified three compounds through drug repurposing that showed strong inhibitory activity against the main protease of the novel coronavirus. One of these compounds demonstrated potential antiviral activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Wei-Chung Chiou, Jui-Chieh Chen, Yun-Ti Chen, Jinn-Moon Yang, Lih-Hwa Hwang, Yi-Shuan Lyu, Hsin-Yi Yang, Cheng Huang
Summary: The COVID-19 pandemic has caused a global health crisis, and developing effective treatments is crucial. This study investigates the role of SARS-CoV-2 3CLpro in viral replication and identifies natural compounds PGG and EGCG as potential inhibitors. The findings highlight the therapeutic potentials of PGG and EGCG for treating SARS-CoV-2 infection.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Luna Song, Hehe Bai, Chenyang Liu, Wenjun Gong, Ai Wang, Li Wang, Yi Zhao, Xuan Zhao, Hongfei Wang
Summary: Two light-activated NO donors [RuCl(qn)(Lbpy)(NO)]X were synthesized and characterized using various spectroscopic techniques. One complex showed higher binding constants with human serum albumin and DNA, with HSA acting as a carrier to facilitate NO release from the complexes upon photoirradiation. Confocal imaging successfully demonstrated photo-induced NO release in living cells.
Article
Chemistry, Inorganic & Nuclear
Leilei Xie, Hehe Bai, Luna Song, Chenyang Liu, Wenjun Gong, Wenming Wang, Xuan Zhao, Chie Takemoto, Hongfei Wang
Summary: The study synthesized a water-soluble nitrosylruthenium complex and investigated its binding with human serum albumin. The release and fluorescence imaging of the complex in vivo were studied using photoinduction and crystallography techniques.
INORGANIC CHEMISTRY
(2021)
Article
Biophysics
Fahu He, Kanako Kuwasako, Masayuki Takizawa, Mari Takahashi, Kengo Tsuda, Takashi Nagata, Satoru Watanabe, Akiko Tanaka, Naohiro Kobayashi, Takanori Kigawa, Peter Guntert, Mikako Shirouzu, Shigeyuki Yokoyama, Yutaka Muto
Summary: Matrin-3 is a multifunctional protein with DNA-binding and RNA-binding activities, which are associated with nuclear matrix formation, transcriptional regulation, and mRNA metabolism. Pathogenic mutations in its disordered region cause ALS and FTD, linked to its RNA-binding activity mediated by the RRM domains.
BIOMOLECULAR NMR ASSIGNMENTS
(2022)
Article
Oncology
Yuta Ikami, Kazue Terasawa, Kensaku Sakamoto, Kazumasa Ohtake, Hiroyuki Harada, Tetsuro Watabe, Shigeyuki Yokoyama, Miki Hara-Yokoyama
Summary: This study reveals the direct interaction between Hsc70 and LAMP2A in chaperone-mediated autophagy (CMA), as well as the significance of the two-domain architecture of the lumenal domains of LAMP2A in this interaction.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Wenming Wang, Xiaojia Liu, Yajie Wang, Yuan Wang, Dan Fu, Hongfang Xi, Yi Zhao, Hongfei Wang
Summary: Ferritins can be classified into four subfamilies based on their structural characteristics, but the ferritin from Mycoplasma penetrans possesses unique characteristics and should be categorized as a new subfamily called Mycoplasma Ferritin (Mfr).
CHINESE CHEMICAL LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Hehe Bai, Jia Shi, Qingyu Guo, Wenming Wang, Zhigang Zhang, Yafeng Li, Manohar Vennampalli, Xuan Zhao, Hongfei Wang
Summary: An Fe(II) complex with DPA-Bpy as the ligand was synthesized and characterized, and its binding properties with DNA and HSA were evaluated. The complex showed cleavage ability towards DNA and significant inhibitory effect on cell proliferation, inducing cell apoptosis.
FRONTIERS IN CHEMISTRY
(2022)
Article
Engineering, Biomedical
Eiji Kobayashi, Aishun Jin, Hiroshi Hamana, Kiyomi Shitaoka, Kazuto Tajiri, Seisuke Kusano, Shigeyuki Yokoyama, Tatsuhiko Ozawa, Tsutomu Obata, Atsushi Muraguchi, Hiroyuki Kishi
Summary: By analyzing T cells at the single-cell level on a microwell array, researchers discovered that T-cell activation can occur via both trans and cis interactions, and successfully cloned tumor-antigen-specific TCRs.
NATURE BIOMEDICAL ENGINEERING
(2022)
Article
Biophysics
Kanako Kuwasako, Sakura Suzuki, Nobukazu Nameki, Masayuki Takizawa, Mari Takahashi, Kengo Tsuda, Takashi Nagata, Satoru Watanabe, Akiko Tanaka, Naohiro Kobayashi, Takanori Kigawa, Peter Guentert, Mikako Shirouzu, Shigeyuki Yokoyama, Yutaka Muto
Summary: The structure and sequence characteristics of the KH domain of mtRbfA were studied, and differences were found compared to RbfA, which may be related to its function in ribosome biogenesis.
BIOMOLECULAR NMR ASSIGNMENTS
(2022)
Article
Biochemistry & Molecular Biology
K. Dhanalakshmi, Seiki Kuramitsu, Shigeyuki Yokoyama, Kumarevel Thirumananseri, Karthe Ponnuraj
Summary: This study reports the crystal structure of arginase from Thermus thermophilus (TtArginase), and compares it with other homologous structures. The results show that TtArginase is more stable compared to its mesophilic counterpart, Bacillus subtilis arginase (BsArginase). Additionally, the study reveals the critical role of metal ions in both the catalytic function and maintenance of proper active site geometry. These findings are important for optimizing the enzymatic action of arginase in various conditions.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
K. Dhanalakshmi, Seiki Kuramitsu, Shigeyuki Yokoyama, Thirumananseri Kumarevel, Karthe Ponnuraj
Summary: The crystal structure of pyrrolidone carboxyl peptidase from Thermus thermophilus (TtPCP) was solved and refined at 1.9 angstrom resolution using the molecular replacement method. Comparing TtPCP with its structural homologs, it was found that the putative thermal stability of TtPCP may be attributed to more intra and inter-molecular hydrogen bonds, hydrophobic and ion pair interactions. This structural information of TtPCP can contribute to understanding the intrinsic stability of thermophilic proteins and can be useful for protein engineering.
BIOPHYSICAL CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Wenming Wang, Yuan Wang, Hongfang Xi, Zidan Song, Wenlong Zhang, Leilei Xie, Danyang Ma, Nan Qin, Hongfei Wang
Summary: The extension peptide (EP) is a unique feature of mature plant ferritin and may have protease activity related to iron uptake and release. Our study on the crystal structure of ferritin-1 from Setaria italica revealed that the EP in this monocotyledon plant had a different folding pattern than other plant ferritins, suggesting a novel fold pattern for EPs in monocotyledons. Additionally, our study found additional iron atoms binding in the fourfold channels, highlighting the important role of these channels in iron diffusion.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mutsuko Kukimoto-Niino, Kentaro Ihara, Chiemi Mishima-Tsumagari, Mio Inoue, Yoshinori Fukui, Shigeyuki Yokoyama, Mikako Shirouzu
Summary: This study reveals the crystal structures of the catalytic DHR2 domain of mouse DOCK10, complexed with either Cdc42 or Rac1, and uncovers the unique dual activation mechanism of DOCK10.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Tatsuo Yanagisawa, Eiko Seki, Hiroaki Tanabe, Yoshifumi Fujii, Kensaku Sakamoto, Shigeyuki Yokoyama
Summary: Pairs of pyrrolysyl-tRNA synthetase (PylRS) and tRNA(Pyl) from Methanosarcina mazei and Methanosarcina barkeri are used for site-specific incorporations of non-canonical amino acids into proteins. Mutations in Methanomethylophilus alvus PylRS allow efficient binding with N-e-((((E)-cyclooct-2-en-1-yl)oxy)carbonyl)-L-lysine (TCO*Lys) but not with N-e-(p-ethynylbenzyloxycarbonyl)-L-lysine (pEtZLys).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hehe Bai, Wenjun Gong, Yating Pang, Chaoyang Shi, Zhigang Zhang, Lili Guo, Yafeng Li, Wenming Wang, Hongfei Wang
Summary: Three isomeric nitrosylruthenium complexes were synthesized and their crystal structures were determined. The complexes showed inhibition of HeLa cell proliferation and induced cell apoptosis and cell cycle arrest. Binding constants with DNA and HSA were evaluated, and HSA was found to be a potential nano-delivery system. This study provides a framework for the rational design of metal-based drugs.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Immunology
Seisuke Kusano, Sho Ueda, Daisuke Oryoji, Aya Toyoumi, Akiko Hashimoto-Tane, Hiroyuki Kishi, Hiroshi Hamana, Atsushi Muraguchi, Hui Jin, Hisashi Arase, Hiroko Miyadera, Reiko Kishikawa, Yasunobu Yoshikai, Hisakata Yamada, Ken Yamamoto, Yasuharu Nishimura, Takashi Saito, Takehiko Sasazuki, Shigeyuki Yokoyama
Summary: Cry j 1 is a major allergen in Japanese cedar pollens. The NF region of Cry j 1 peptide plays a role in enhancing T-cell activation. Mutation of Ser and Lys in the NF region to Glu reduces the affinity for HLA-DP5, antigen presentation, and T-cell activation.
INTERNATIONAL IMMUNOLOGY
(2023)