Article
Virology
Li He, Guangyan Zhou, Vladimir Sofiyev, Eddie Garcia, Newton Nguyen, Kathy H. H. Li, Miriam Gochin
Summary: The study investigates the conversion of molecules with better drug-like properties to improve antiviral efficacy. By adding an electrophilic warhead, equilibrium binders can be converted into inhibitors. This method shows promise in inhibiting HIV-1 entry.
Article
Pharmacology & Pharmacy
Jing Pu, Yu Dai, Qian Wang, Lu Lu, Junqi Zhang, Wei Xu, Lan Xie, Shengqi Wang, Fei Yu, Xiaoyang He, Shibo Jiang
Summary: Virus inactivator FD028, a new small-molecule HIV-1 inactivator, shows promising activity in inactivating cell-free virions at moderate nanomolar concentrations by targeting both gp120 and gp41 regions of HIV-1. With broad-spectrum inhibition and minimal cytotoxicity, FD028 has potential for further development as an HIV-1 inactivator-based therapeutic.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Wei Xu, Zhe Cong, Qianyu Duan, Qian Wang, Shan Su, Rui Wang, Lu Lu, Jing Xue, Shibo Jiang
Summary: A protein-based, long-acting HIV fusion inhibitor called FLT was designed and constructed, which binds with human serum albumin in a reversible manner to prolong the half-life of the HIV fusion inhibitor T1144. FLT showed high efficiency in inhibiting HIV infection and is considered a promising candidate for a new protein-based anti-HIV drug.
Article
Biochemistry & Molecular Biology
Yue Hu, Wenjiang Yu, Xiuzhu Geng, Yuanmei Zhu, Huihui Chong, Yuxian He
Summary: In this study, we investigated the effect of C16 modification on the resistance barrier of the inhibitor LP-40. The results showed that the LP-40 activity is enhanced and that it has a high resistance barrier. LP-40 and T20 have similar resistance mutation sites.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mario Cano-Munoz, Julie Lucas, Li-Yun Lin, Samuele Cesaro, Christiane Moog, Francisco Conejero-Lara
Summary: This study identified the vulnerability of the gp41 C-terminal heptad repeat to inhibition and demonstrated that engineering stable miniproteins can enhance inhibitory potency against HIV-1. These findings have implications in the development of new strategies to inhibit HIV targeting the gp41 CHR region.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Caelan E. Radford, Philipp Schommers, Lutz Gieselmann, Katharine H. D. Crawford, Bernadeta Dadonaite, Timothy C. Yu, Adam S. Dingens, Julie Overbaugh, Florian Klein, Jesse D. Bloom
Summary: Understanding the specificities of human serum antibodies that neutralize HIV can inform prevention and treatment strategies. A deep mutational scanning system was developed to measure the effects of mutations to HIV envelope on antibody neutralization. The study found that different polyclonal serum show neutralizing activity against HIV by targeting various epitopes, similar to characterized monoclonal antibodies. Mapping the specificity of neutralizing activity in polyclonal serum will help in evaluating anti-HIV immune responses for prevention strategies.
CELL HOST & MICROBE
(2023)
Article
Biology
Christophe Caillat, Delphine Guilligay, Johana Torralba, Nikolas Friedrich, Jose L. Nieva, Alexandra Trkola, Christophe J. Chipot, Francois L. Dehez, Winfried Weissenhorn
Summary: The study presents the crystal structure of HIV-1 gp41 locked in a fusion intermediate state by a neutralizing antibody, showing the structural plasticity and conformational flexibility of membrane anchors. Molecular dynamics simulation suggests a possible transition pathway into the final post-fusion conformation, highlighting the potential of MPER-specific broadly neutralizing antibodies to block membrane fusion.
Article
Chemistry, Multidisciplinary
Guangyan Zhou, Li He, Kathy H. Li, Cassio C. S. Pedroso, Miriam Gochin
Summary: The study presented a low molecular weight covalent inhibitor targeting a conserved lysine residue within the hydrophobic pocket of HIV-1 glycoprotein-41, which exhibited significantly enhanced anti-viral activity compared to its non-covalent counterpart. This represents a major advancement in the quest for non-peptide fusion inhibitors.
CHEMICAL COMMUNICATIONS
(2021)
Article
Microbiology
Ana Valades-Alcaraz, Roberto Reinosa, Africa Holguin
Summary: This study provides a comprehensive conservation analysis of gp41/gp36 variants in the largest panel of HIV variants to date, offering valuable information for the rational design of drugs, vaccines, and molecular detection tests targeting the HIV transmembrane glycoprotein.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rongyi Wang, Kohei Tsuji, Takuya Kobayakawa, Yishan Liu, Kazuhisa Yoshimura, Shuzo Matsushita, Shigeyoshi Harada, Hirokazu Tamamura
Summary: This study developed hybrid molecules containing small CD4 mimics and gp41-C-terminal heptad repeat-related peptides, and compared the efficacy of different synthesis methods. The results showed that these hybrid molecules have dual targets and significantly inhibit HIV activity.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Igor de la Arada, Johana Torralba, Igor Tascon, Adai Colom, Iban Ubarretxena-Belandia, Jose L. R. Arrondo, Beatriz Apellaniz, Jose L. Nieva
Summary: Envelope glycoproteins from genetically-divergent virus families contain fusion peptides that can insert into and disrupt target cell membranes during virus-cell fusion. Membrane-proximal external regions (MPERs) have been implicated in promoting the viral membrane restructuring event required for fusion, but it is unclear whether the structure-function relationships governing canonical fusion peptides also apply to MPER sequences.
SCIENTIFIC REPORTS
(2021)
Article
Virology
Daniel P. Leaman, Armando Stano, Yajing Chen, Lei Zhang, Michael B. Zwick
Summary: The study introduces a novel multivalent mEnv vaccine platform called MELs, which does not require protein engineering or extraneous proteins. Through a sequential immunization scheme in rabbits, MELs were able to elicit antibodies that neutralized tier 2 HIV isolates.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Blandine Noailly, Melyssa Yaugel-Novoa, Justine Werquin, Fabienne Jospin, Daniel Drocourt, Thomas Bourlet, Nicolas Rochereau, Stephane Paul
Summary: Broadly neutralizing antibodies (bNAbs) show promising potential for HIV-1 prevention. Different bNAb isotypes have varying abilities in viral neutralization and ADCC-like activity. These findings contribute to the search for new treatments and antibody-based vaccines.
Article
Multidisciplinary Sciences
David C. Montefiori, Maria V. Filsinger Interrante, Benjamin N. Bell, Adonis A. Rubio, Joseph G. Joyce, John W. Shiver, Celia C. LaBranche, Peter S. Kim
Summary: Research has shown that the neutralization activity of the well-characterized NHR-targeting antibody D5 is significantly enhanced in TZM-bl cells expressing Fc gamma RI, resulting in potent neutralization of tier-2 viruses. Moreover, guinea pig antisera immunized with the NHR-based vaccine candidate (ccIZN36)(3) neutralized tier-2 viruses from multiple clades in an Fc gamma RI-dependent manner, suggesting the potential importance of targeting Fc gamma RI in the development of a prophylactic HIV-1 vaccine.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Xinling Wang, Miao Cao, Yanling Wu, Wei Xu, Qian Wang, Tianlei Ying, Lu Lu, Shibo Jiang
Summary: Despite the progress made with HAART therapy, challenges remain for the treatment of HIV-1 virus. Studies have shown that combining a gp120 binding protein and a gp41 binding antibody may have a synergistic effect in inhibiting the spread of HIV-1.
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)
Letter
Cell Biology
Shuai Xia, Jasper Fuk-Woo Chan, Lijue Wang, Fanke Jiao, Kenn Ka-Heng Chik, Hin Chu, Qiaoshuai Lan, Wei Xu, Qian Wang, Chao Wang, Kwok-Yung Yuen, Lu Lu, Shibo Jiang
Editorial Material
Immunology
Shan Su, Weihua Li, Shibo Jiang
Summary: The simultaneous presence of SARS-CoV-2 and MERS-CoV raises concerns about the potential emergence of new beta-coronavirus strains with high transmissibility similar to SARS-CoV-2 and high mortality rates similar to MERS-CoV. Therefore, there is an urgent need to develop pan-beta-CoV vaccines capable of targeting not only current variants of concern, but also potential future coronaviruses resembling SARS-CoV-3 or MERSCoV-2.
TRENDS IN IMMUNOLOGY
(2022)
Article
Virology
Naru Zhang, Kangchen Li, Zezhong Liu, Kutty Selva Nandakumar, Shibo Jiang
Summary: This article focuses on the research progress and achievements of adjuvanted COVID-19 subunit and inactivated vaccines, and compares the advantages and disadvantages of different adjuvant formulations, aiming to provide a scientific reference for designing an effective strategy for future vaccine development.
Article
Microbiology
Xinling Wang, Wei Xu, Zezhong Liu, Yanling Wu, Qian Wang, Miao Cao, Tianlei Ying, Na He, Lu Lu, Shibo Jiang
Summary: In this study, a dual-targeting recombinant protein, DL35D, was designed and constructed to simultaneously target HIV-1 virus and latent cells. DL35D-DM1, produced by linking the DM1 toxin to DL35D, showed inhibitory and inactivation activity against HIV-1 infection and effectively killed HIV-1-infected cells and LRA-reactivated latent cells, making it a promising candidate for the development of a novel antiviral drug for potential HIV functional cure.
Article
Immunology
Xun Wang, Xiaoyu Zhao, Jieyu Song, Jing Wu, Yuqi Zhu, Minghui Li, Yuchen Cui, Yanjia Chen, Lulu Yang, Jun Liu, Huanzhang Zhu, Shibo Jiang, Pengfei Wang
Summary: This study found that the Omicron variant is highly resistant to neutralization by sera from convalescents or individuals vaccinated with two doses of inactivated whole-virion vaccines. However, a homologous or heterologous booster significantly increased neutralization titers. Additionally, the Omicron variant resists most monoclonal antibodies targeting distinct epitopes. These findings highlight the importance of pushing forward booster vaccinations to combat emerging SARS-CoV-2 variants.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Biochemistry & Molecular Biology
Cheng Li, Wuqiang Zhan, Zhenlin Yang, Chao Tu, Gaowei Hu, Xiang Zhang, Wenping Song, Shujuan Du, Yuanfei Zhu, Keke Huang, Yu Kong, Meng Zhang, Qiyu Mao, Xiaodan Gu, Yi Zhang, Youhua Xie, Qiang Deng, Yuanlin Song, Zhenguo Chen, Lu Lu, Shibo Jiang, Yanling Wu, Lei Sun, Tianlei Ying
Summary: This study identifies two highly conserved regions on the Omicron variant receptor-binding domain that are recognized by broadly neutralizing antibodies, and generates a bispecific antibody that can simultaneously bind these regions, showing excellent therapeutic efficacy and neutralization breadth.
Article
Chemistry, Medicinal
Huan Wang, Xinling Wang, Jiahui Li, Qing Li, Siliang Feng, Lu Lu, Chao Wang, Shibo Jiang
Summary: Both the deep pocket region and its neighboring subpocket site on the N-trimer of HIV-1 gp41 protein can be targeted for the development of HIV-1 entry inhibitors. This study reports the design of alpha-helical lipopeptides with non-native protein sequences as highly active HIV-1 fusion inhibitors that can occupy both the deep pocket and subpocket sites.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Virology
Naru Zhang, Qianting Ji, Zezhong Liu, Kaiming Tang, Yubin Xie, Kangchen Li, Jie Zhou, Sisi Li, Haotian Shang, Zecan Shi, Tianyu Zheng, Jiawei Yao, Lu Lu, Shuofeng Yuan, Shibo Jiang
Summary: The nanoparticle manganese adjuvant enhances the immunogenicity of protein-based COVID-19 subunit vaccines, inducing high levels of antibodies and effectively reducing viral load.
Article
Chemistry, Medicinal
Wei Xu, Zhe Cong, Qianyu Duan, Qian Wang, Shan Su, Rui Wang, Lu Lu, Jing Xue, Shibo Jiang
Summary: A protein-based, long-acting HIV fusion inhibitor called FLT was designed and constructed, which binds with human serum albumin in a reversible manner to prolong the half-life of the HIV fusion inhibitor T1144. FLT showed high efficiency in inhibiting HIV infection and is considered a promising candidate for a new protein-based anti-HIV drug.
Article
Virology
Xiaoyu Zhao, Cun Li, Man Chun Chiu, Rui Qiao, Shibo Jiang, Pengfei Wang, Jie Zhou
Summary: In this study, potent inhibitors against EV-A71 infection were identified through screening a kinase inhibitor library. Among the hits, the Rock inhibitor GSK269962A was found to efficiently suppress EV-A71 replication in RD cells and human intestinal organoids in a dose-dependent manner. Knockdown of Rock1, but not Rock2, significantly restricted viral replication in RD cells, suggesting that Rock1 could serve as a novel host dependency factor and target for the development of anti-EV-A71 therapeutics.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Virology
Chao Wang, Qing Li, Lujia Sun, Xinling Wang, Huan Wang, Wenpeng Zhang, Jiahui Li, Yang Liu, Lu Lu, Shibo Jiang
Summary: Researchers developed a novel dual-target inhibitor by integrating a small-molecule HIV-1 inhibitor with an artificial peptide. This inhibitor showed improved activity against multiple drug-resistant HIV-1 strains.
Article
Biochemistry & Molecular Biology
Ling Xu, Chao Wang, Wei Xu, Lixiao Xing, Jie Zhou, Jing Pu, Mingming Fu, Lu Lu, Shibo Jiang, Qian Wang
Summary: By replacing the PEG linker in EK1C4 with a short peptide, we designed and synthesized a dePEGylated lipopeptide, EKL1C, which showed potent inhibitory activity against coronaviruses, including SARS-CoV-2, and HIV-1. This indicates that HR1 may serve as a common target for the development of broad-spectrum viral fusion inhibitors, and EKL1C has potential clinical application as a therapeutic or preventive agent against coronavirus, HIV-1, and other class I enveloped viruses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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.
Article
Biology
Shan Su, Wei Xu, Shibo Jiang
Summary: The approval of enfuvirtide represents a significant advancement in the development of virus entry inhibitor-based antiviral therapeutics. Peptide-, small-molecule-, and protein-based entry inhibitors have since been identified and approved for viral diseases. This review highlights the future trend of these antivirals and discusses the advantages and disadvantages associated with each type.
VIRUS ENTRY INHIBITORS: Stopping the Enemy at the Gate
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
