Article
Chemistry, Medicinal
Chao Wang, Xinling Wang, Huan Wang, Jing Pu, Qing Li, Jiahui Li, Yang Liu, Lu Lu, Shibo Jiang
Summary: This study reports a dual-targeted drug compound with bifunctional entry inhibitors that effectively block HIV-1 entry. One chimera, CP12TAK, shows potent antiviral activity against both R5-tropic viruses and X4-tropic HIV-1 strains, suggesting promising potential for further development as a new anti-HIV-1 drug. Results indicate that this strategy could be extended to design therapies against infection of other enveloped viruses.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Avijit Sardar, Aritraa Lahiri, Mithila Kamble, Amirul I. Mallick, Pradip K. Tarafdar
Summary: The study identified a lipopeptide inspired by Mycobacterium, which effectively inhibits viral entry by modulating parameters such as interfacial order and surface potential during membrane fusion. This lipopeptide was successfully tested to combat influenza virus and coronavirus infections in experiments.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Pharmacology & Pharmacy
Renata Boldin, Bianca Cestari Zychar, Luis Roberto C. Goncalves, Juliana Mozer Sciani
Summary: In this study, a peptide derived from a marine fish was evaluated for its binding affinity to BACE-1 and pharmacokinetic properties. The peptide was found to stably bind to BACE-1 and competitively inhibit its activity, leading to a reduction in the production of beta-amyloid 42. It distributed rapidly to various tissues in mice without accumulation and could cross the blood-brain barrier to reach the brain. Histological analysis showed the peptide to be non-toxic.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Kailu Yang, Chuchu Wang, Alex J. B. Kreutzberger, Ravi Ojha, Suvi Kuivanen, Sergio Couoh-Cardel, Serena Muratcioglu, Timothy J. Eisen, K. Ian White, Richard G. Held, Subu Subramanian, Kendra Marcus, Richard A. Pfuetzner, Luis Esquivies, Catherine A. Doyle, John Kuriyan, Olli Vapalahti, Giuseppe Balistreri, Tom Kirchhausen, Axel T. Brunger
Summary: A newly designed extended HR2 peptide has been shown to effectively inhibit the infection of SARS-CoV-2 and its variants, demonstrating a higher antiviral efficacy. This finding may provide new insights for the development of novel therapeutic drugs targeting SARS-CoV-2 and other related viruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Deokhee Kang, Do-Wook Kim, Joo-Chan Kim, Hee-Sung Park
Summary: To facilitate the discovery of peptide-based drugs, researchers developed a screening platform called CWCPS, which successfully identified a potent inhibitor called CY5-6Q that targets HDAC8 with a K-D value of 15 nM. This approach could serve as a versatile and general platform for discovering cyclic peptide inhibitors.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Microbiology
Ippei Yoshida, Kaho Arikawa, Yusuke Honma, Shoko Inatani, Mitsukane Yoshinaga, Hiroyuki Sugiyama
Summary: The novel macrocyclic compound TP0591816 showed significant antiviral activities against both subgroup A and subgroup B RSV, inhibiting fusion of the virus with the cell membrane during viral entry and reducing lung virus titers in a dose-dependent manner. It also maintained its antiviral activity against a fusion inhibitor-resistant RSV strain, indicating its potential as a promising candidate for the treatment of resistant RSV infection.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Robotics
Zhen Yang, Zheng Gong, Yonggang Jiang, Yueri Cai, Zhiqiang Ma, Xin Na, Zihao Dong, Deyuan Zhang
Summary: In this study, the authors proposed a maximized hydrodynamic stimulation strategy for sensor placement optimization and successfully built an artificial lateral line (ALL) system mimicking a small fish model. Experimental results showed that the system performed well in yaw angle detection, comparable to the perception ability of cave fish. This sensor placement strategy has practical application value for equipping bionic robotic fish and other underwater vehicles.
IEEE ROBOTICS AND AUTOMATION LETTERS
(2022)
Article
Cell Biology
Liying Feng, Kai Chen, Wei Huang, Yuelong Jiang, Xihuan Sun, Yong Zhou, Li Li, Yin Li, Xianming Deng, Bing Xu
Summary: The novel dual-target inhibitor HZX-02-059 showed highly cytotoxic activity against double-hit lymphoma cell lines through caspase-independent cell death, methuosis. It induced cell death by targeting the PIKfyve/TFEB axis and inhibiting tubulin and mTOR/Myc axis-induced cell cycle arrest.
CELL DEATH DISCOVERY
(2022)
Article
Chemistry, Multidisciplinary
Ye Wu, Yan Zou, Lingling Sun, Alfredo Garzino-Demo, Honggang Hu, Weidong Zhang, Xiang Li
Summary: In this study, a double side-chains retention hydrocarbon stapling strategy was developed and successfully applied in the synthesis of stapled peptides. This method not only enhanced the conformational stability and protease resistance of peptides, but also preserved the structural characteristics of linear peptides to the maximum extent, which is crucial for anti-HIV-1 activity.
CHINESE CHEMICAL LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Yonglan Liu, Mingzhen Zhang, Hyunbum Jang, Ruth Nussinov
Summary: Bcr-Abl, a nonreceptor tyrosine kinase, plays a crucial role in leukemias, particularly chronic myeloid leukemia (CML). The fusion of Bcr and Abl leads to constitutive activation of Bcr-Abl. Oligomerization of Bcr-Abl is critical for its membrane clustering, MAPK signaling, and cell proliferation. Understanding the structural basis of Bcr-Abl oligomerization can guide the development of novel drugs targeting this process.
Article
Biology
Qingxin Wei, Ruheng Wang, Yi Jiang, Leyi Wei, Yu Sun, Jie Geng, Ran Su
Summary: The study proposes a deep learning framework, ConPep, for predicting peptide contact maps. The framework utilizes a pretrained biological language model and prior knowledge from large scale databases, and incorporates Bidirectional Gated Recurrent Unit and attention mechanisms to improve prediction accuracy and robustness. Experimental results demonstrate the excellent performance of the method on short peptide fragments.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Lin Huang, Xiaozhan Qu, Yao Chen, Weiya Xu, Chengdong Huang
Summary: Efficient production of soluble, properly folded proteins is critical in genomics; a sandwiched-fusion strategy incorporating protein tags at both ends of the target protein can protect against proteolysis; this novel method allows for economical and successful production of labile proteins, and may be widely applicable to other systems.
Review
Oncology
Sarah A. Holstein, Caroline A. Heckman, Faith E. Davies, Gareth J. Morgan, Stefan Svensson Gelius, Fredrik Lehmann
Summary: Aminopeptidases play a crucial role in cellular processes and functions, and their overexpression can facilitate rapid tumor cell proliferation. Inhibiting aminopeptidase activity holds potential as a targeted approach for new oncological treatments.
CURRENT CANCER DRUG TARGETS
(2023)
Article
Biology
Lili Wu, Anqi Zheng, Yangming Tang, Yan Chai, Jiantao Chen, Lin Cheng, Yu Hu, Jing Qu, Wenwen Lei, William Jun Liu, Guizhen Wu, Shaogui Zeng, Hang Yang, Qihui Wang, George Fu Gao
Summary: Scientists designed a derivative called P315V3, which showed the most efficient antiviral activity against SARS-CoV-2 variants and other coronaviruses. It also demonstrated effective prophylactic efficacy against the Delta and Omicron variants in mice. These findings highlight the potential of P315V3 as a nasal pan-SARS-CoV-2 or pan-coronavirus inhibitor for preventing or treating coronavirus diseases.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Yanfei Liu, Lili Gan, Peili Feng, Lei Huang, Luoying Chen, Shuhua Li, Hui Chen
Summary: Artificial carboxylesterases specific for short chain fatty acids were constructed via peptide self-assembly. The designed peptides self-assembled into nanofibers with an active center composed of extending histidine units and hydrophobic edge.
FRONTIERS IN CHEMISTRY
(2022)
Letter
Immunology
Xinling Wang, Wei Xu, Gaowei Hu, Shuai Xia, Zhiping Sun, Zezhong Liu, Youhua Xie, Rong Zhang, Shibo Jiang, Lu Lu
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Review
Virology
Qiaoshuai Lan, Lijue Wang, Fanke Jiao, Lu Lu, Shuai Xia, Shibo Jiang
Summary: This review summarizes the recent development of pan-coronavirus fusion inhibitors targeting SARS-CoV-2 and its variants, highlighting their potential application in combating COVID-19 infection, reinfection, and future emerging coronavirus infectious diseases.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Review
Virology
Jie Zhou, Zezhong Liu, Guangxu Zhang, Wei Xu, Lixiao Xing, Lu Lu, Qian Wang, Shibo Jiang
Summary: The emergence of new SARS-CoV-2 variants poses a challenge to current vaccines, highlighting the need for broad-spectrum vaccines that can address these variants, sarbecoviruses, and beta-CoVs. This review discusses the target antigens and protective efficacy of current SARS-CoV-2 vaccines, as well as recent advances in broad-spectrum vaccines against sarbecoviruses and beta-CoVs.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Letter
Cell Biology
Simeng Zhao, Fengjiang Liu, Shizhen Qiu, Qiaoshuai Lan, Yiran Wu, Wei Xu, Junzi Ke, Jie Yang, Xiaoyan Liu, Kun Wang, Hangtian Guo, Shuai Xia, Fangfang Zhang, Jiabei Wang, Xiaowen Hu, Lu Lu, Shibo Jiang, Suwen Zhao, Lianxin Liu, Youhua Xie, Xiuna Yang, Haopeng Wang, Guisheng Zhong
Article
Microbiology
Lu Meng, Jialu Zha, Bingjie Zhou, Long Cao, Congli Jiang, Yuanfei Zhu, Teng Li, Lu Lu, Junqi Zhang, Heng Yang, Jian Feng, Zhifeng Gu, Hong Tang, Lubin Jiang, Dianfan Li, Dimitri Lavillette, Xiaoming Zhang
Summary: A monoclonal antibody (Ab08) isolated from a convalescent patient effectively neutralizes SARS-CoV-2 and its variants, and shows therapeutic potential in infected mice.
Article
Biochemistry & Molecular Biology
Ming Xiao, Fubo Ma, Jun Yu, Jianghang Xie, Qiaozhen Zhang, Peng Liu, Fei Yu, Yuming Jiang, Le Zhang
Summary: This study proposes a novel accurate strand-specific SARS-CoV-2 intra-host mutation spectra computation method, develops an efficient and fast SARS-CoV-2 intra-host mutation simulation method based on mutation spectra, and establishes an online analysis and visualization platform. The main results include: significant variability in the SARS-CoV-2 intra-host mutation spectra across different lineages, with major mutations occurring on both the positive and negative sense strands; our mutation simulation reveals a deviation from the base content percentage of Alpha-CoV/Delta-CoV after approximately 620 mutation steps; 2019-NCSS provides an easy-to-use and visualized online platform for SARS-Cov-2 analysis and mutation simulation.
Article
Chemistry, Medicinal
Chao Wang, Huan Wang, Xinling Wang, Lujia Sun, Qian Wang, Qing Li, Ruiying Liang, Dou Dou, Fei Yu, Lu Lu, Shibo Jiang
Summary: A multitarget-directed ligand strategy was used to develop a series of short-peptide HIV-1 entry inhibitors that combined the pharmacological activities of a peptide fusion inhibitor and a small-molecule CCR5 antagonist. The dual-target 23-residue peptides SP12T and SP12L showed significantly increased inhibitory activities against HIV-1 replication compared to the marketed 36-residue peptide T20. These short-peptide-based HIV-1 entry inhibitors have the potential to be further developed as candidates for novel multitarget therapy for HIV-1 infection.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Shuai Xia, Lijue Wang, Fanke Jiao, Xueying Yu, Wei Xu, Ziqi Huang, Xicheng Li, Qian Wang, Yun Zhu, Qiuhong Man, Shibo Jiang, Lu Lu
Summary: The continuous emergence of Omicron variant and its subvariants has led to an increasing number of infections, reinfections, and vaccine-breakthrough infections, posing a serious threat to human health. Several new Omicron subvariants with distinct mutation profiles in their spike proteins have shown enhanced ability to evade vaccine-induced immunity, increased infectivity, and transmissibility, becoming dominant sublineages. The study found that these novel Omicron subvariants have more efficient membrane fusion kinetics compared to the original variant, indicating increased pathogenicity. Peptide-based pan-CoV fusion inhibitors, EK1 and EK1C4, were found to be effective against membrane fusion and infection mediated by the S proteins of these Omicron subvariants. Immune sera induced by wild-type SARS-CoV-2 RBD-based vaccine or BA.2 convalescent sera showed synergism with EK1 against both wild-type SARS-CoV-2 and various Omicron subvariants, suggesting EK1-based fusion inhibitors as promising candidates for clinical antiviral agents against circulating Omicron subvariants.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Immunology
Tianyu Lu, Qiuhong Man, Xueying Yu, Shuai Xia, Lu Lu, Shibo Jiang, Lize Xiong
Summary: A prognostic model based on immune variables was developed and validated to early recognize potentially severe cases of Omicron variant-infected patients. Six predictors, including age, neutrophils, lymphocytes, procalcitonin, IL-2, and IL-10, were selected to establish the model. The model showed satisfactory high discrimination, calibration, and net benefit, indicating its potential use in reducing the severity and mortality of Omicron variant infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Songyi Xue, Wei Xu, Lei Wang, Xinling Wang, Qianyu Duan, Laurent Calcul, Shaohui Wang, Wenqi Liu, Xingmin Sun, Lu Lu, Shibo Jiang, Jianfeng Cai
Summary: We report a series of helical peptidomimetics, D-sulfonyl-gamma-AApeptides, which effectively mimic the key residues of heptad repeat 2 and interact with heptad repeat 1 in the SARS-CoV-2 S2 subunit, resulting in inhibiting SARS-CoV-2 spike protein-mediated fusion between virus and cell membranes. The leads also displayed broad-spectrum inhibitory activity against a panel of other human CoVs and showed strong potency in vitro and in vivo. Meanwhile, they also demonstrated complete resistance to proteolytic enzymes or human sera and exhibited extremely long half-life in vivo and highly promising oral bioavailability, delineating their potential as pan-CoV fusion inhibitors with the potential to combat SARS-CoV-2 and its variants.
ACS CENTRAL SCIENCE
(2023)
Article
Biology
Fanlin Li, Wei Xu, Xiaoqing Zhang, Wanting Wang, Shan Su, Ping Han, Haiyong Wang, Yanqin Xu, Min Li, Lilv Fan, Huihui Zhang, Qiang Dai, Hao Lin, Xinyue Qi, Jie Liang, Xin Wang, Shibo Jiang, Youhua Xie, Lu Lu, Xuanming Yang
Summary: Neutralizing antibodies are not as effective in therapeutic models as in prophylactic models due to limited efficacy in eliminating virus-producing cells. A SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy is presented, which blocks viral entry and eliminates infected cells through T cell-mediated cytotoxicity. S-BiTE is effective against both original and Delta variants of SARS-CoV-2, suggesting potential application against immune-escaping variants. In a humanized mouse model with live SARS-CoV-2 infection, S-BiTE significantly reduces viral load compared to neutralization treatment only.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Xinling Wang, Lujia Sun, Zezhong Liu, Lixiao Xing, Yun Zhu, Wei Xu, Shuai Xia, Lu Lu, Shibo Jiang
Summary: This study reports the development of a recombinant protein called HR1LS, which inhibits the fusion and entry of human coronaviruses into host cells and generates neutralizing antibodies. It is considered a promising candidate for the treatment and prevention of infections caused by SARS-CoV-2 and other potentially infectious coronaviruses.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Biochemistry & Molecular Biology
Xiaojie Su, Ziqi Huang, Wei Xu, Qian Wang, Lixiao Xing, Lu Lu, Shibo Jiang, Shuai Xia
Summary: The peptide-based pan-coronavirus fusion inhibitor EK1 is showing promising clinical application prospects against SARS-CoV-2 and its variants. By conjugating EK1 with the human immunoglobulin G Fc-binding peptide (IBP), the engineered peptide IBP-EK1 demonstrates broad-spectrum inhibitory activity against various coronaviruses with improved in vivo half-life. It also shows synergistic effects when combined with monoclonal neutralizing antibodies, suggesting its potential as a long-acting, broad-spectrum antiviral agent against COVID-19 and future highly pathogenic coronaviruses.
