Article
Chemistry, Medicinal
Natalie Losada, Francesc X. Ruiz, Francesca Curreli, Kevin Gruber, Alyssa Pilch, Kalyan Das, Asim K. Debnath, Eddy Arnold
Summary: This study focuses on compounds (NBD derivatives) originally developed to bind to HIV-1 gp120, some of which inhibit RT. Crystal structures of three NBD compounds in complex with HIV-1 RT have been determined, correlating with RT enzyme inhibition and antiviral activity, to develop structure-activity relationships. Two lead compounds, NBD-14189 and NBD-14270, show potent antiviral activity and low cytotoxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Wei Pang, Ying Lu, Yan-Bo Zhao, Fan Shen, Chang-Fa Fan, Qian Wang, Wen-Qiang He, Xiao-Yan He, Ze-Kai Li, Tao-Tao Chen, Cui-Xian Yang, You-Zhi Li, Si-Xuan Xiao, Zu-Jiang Zhao, Xu-Sheng Huang, Rong-Hua Luo, Liu-Meng Yang, Mi Zhang, Xing-Qi Dong, Ming-Hua Li, Xiao-Li Feng, Qing-Cui Zhou, Wang Qu, Shibo Jiang, Songying Ouyang, Yong-Tang Zheng
Summary: The emerging SARS-CoV-2 variants are weakening the efficacy of current vaccines and antibody therapeutics. Researchers have developed a recombinant subunit vaccine, HR121, which targets a conserved region in the S protein. This vaccine generates highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, providing effective protection.
Article
Chemistry, Medicinal
Olaia Marti-Mari, Belen Martinez-Gualda, Irene Fernandez-Barahona, Alberto Mills, Rana Abdelnabi, Sam Noppen, Johan Neyts, Dominique Schols, Maria-Jose Camarasa, Fernando Herranz, Federico Gago, Ana San-Felix
Summary: Recently, we have discovered a novel family of compounds that are smaller in size and possess dual anti-HIV and anti-EV71 activities. Some of the derivatives showed greater potency and selectivity against HIV-1, HIV-2, and EV-A71 compared to the prototype compound AL-470. A fluorescent probe exhibited specific tropism for the intestines and lungs, which are important niches for the human microbiome in health and disease.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Matthew Weichseldorfer, Marvin Reitz, Olga S. Latinovic
Summary: Combined antiretroviral therapy (cART) is widely recommended for controlling HIV-1 replication and improving the quality of life of infected individuals. However, latent infected cells remain a major barrier to treatment efficacy in the long term.
Article
Cell Biology
Viktoria Stab, Christiane Stahl-Hennig, Armin Ensser, Elie Richel, Kirsten Fraedrich, Ulrike Sauermann, Bettina Tippler, Florian Klein, Dennis R. Burton, Matthias Tenbusch, Klaus Uberla
Summary: Neutralizing antibodies targeting HIV-1 Env can protect from systemic infection by blocking the entry of the virus into target cells during the first replication cycle. This mode of protection may be the most effective in preventing the formation of latently infected cells and the emergence of antibody-resistant mutants.
CELL REPORTS MEDICINE
(2023)
Article
Microbiology
Eva Mittler, Tanwee Alkutkar, Rohit K. Jangra, Kartik Chandran
Summary: Researchers introduced a novel in situ assay to monitor the binding of GPCL-NPC1 in intact, infected cells. This assay, based on DNA-assisted, antibody-mediated proximity ligation, allows for visualization of binding complexes and helps dissect the interaction between the Ebola virus glycoprotein and its receptor NPC1.
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
Chemistry, Medicinal
Shengchao Zhou, Kun Wang, Ziwei Hu, Tao Chen, Yao Dong, Rongmei Gao, Mengyuan Wu, Yuhuan Li, Xingyue Ji
Summary: This study identified a series of quinazoline derivatives with potent antiviral activity against coronavirus through screening of a compound library. The derivatives showed high selectivity and could be potentially used for further development of antiviral drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, General & Internal
Oriol Mitja, Andrea Alemany, Michael Marks, Jezer I. Lezama Mora, Juan Carlos Rodriguez-Aldama, Mayara Secco Torres Silva, Ever Arturo Corral Herrera, Brenda Crabtree-Ramirez, Jose Luis Blanco, Nicolo Girometti, Valentina Mazzotta, Aniruddha Hazra, Macarena Silva, Juan Jose Montenegro-Idrogo, Kelly Gebo, Jade Ghosn, Maria Fernanda Pena Vazquez, Eduardo Matos Prado, Uche Unigwe, Judit Villar-Garcia, Noah Wald-Dickler, Jason Zucker, Roger Paredes, Alexandra Calmy, Laura Waters, Cristina Galvan-Casas, Sharon Walmsley, Chloe M. Orkin
Summary: In the 2022 multicountry mpox outbreak, 38-50% of those affected were people living with HIV. Clinical outcomes and mortality were worse in people with more advanced HIV.
Review
Microbiology
Jean-Francois Bruxelle, Nino Trattnig, Marianne W. Mureithi, Elise Landais, Ralph Pantophlet
Summary: This review discusses the challenges in developing effective strategies to prevent HIV-1 infection based on insights from the current model of mucosal transmission and cell entry. It examines key viral and host factors, preventive strategies using antibody-mediated protection against T/F viruses and mucosal immunity, and treatment strategies targeting viral entry with a focus on clinically advanced entry inhibitors.
Article
Multidisciplinary Sciences
Chih-Feng Tien, Wan-Ting Tsai, Chun Hwa Chen, Hui-Ju Chou, Mingzi M. Zhang, Jhe-Jhih Lin, En-Ju Lin, Shih-Syong Dai, Yueh-Hsin Ping, Chia-Yi Yu, Yi-Ping Kuo, Wei-Hsiang Tsai, Hsin-Wei Chen, Guann-Yi Yu
Summary: Post-translational modifications play critical roles in protein folding, stability, trafficking, and function. This study investigates the impact of glycosylation and palmitoylation on the maturation and infectivity of SARS-CoV-2 spike protein. The results show that mutations in specific motifs alter intracellular trafficking, glycosylation pattern, and infectivity of pseudoviruses, highlighting the importance of these modifications in the fusion and infection mediated by the S protein.
Article
Biochemistry & Molecular Biology
Jing Xue, Huihui Chong, Yuanmei Zhu, Jingjing Zhang, Ling Tong, Jiahan Lu, Ting Chen, Zhe Cong, Qiang Wei, Yuxian He
Summary: The new HIV fusion-inhibitory lipopeptide LP-98 showed potent antiviral activity in rhesus macaques, with some achieving potential posttreatment control effectiveness.
Article
Virology
Wei Li, Ji Liu, Yuanyuan Liu, Qin Li, Wen Yin, Kevin K. Wanderi, Xiaowei Zhang, Zhiping Zhang, Xian-En Zhang, Zongqiang Cui
Summary: This study reveals the dynamic podosome-mediated entry of HIV-1 into macrophages, where the core and ring structures of podosomes play complex roles in viral entry, with the CCR5 coreceptor recruited to form specific clusters. The podosome facilitates HIV-1 entry with a rotation mode triggered by dynamic actin.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xia Yang, Hailiang Sun, Zhening Zhang, Weixin Ou, Fengxiang Xu, Ling Luo, Yahong Liu, Weisan Chen, Jianxin Chen
Summary: Influenza A virus (IAV) infections pose a serious threat to public health and there is an urgent need for novel anti-IAV medications. This study reveals that ginsenoside rk1 (G-rk1) and G-rg5, derived from panax ginseng, exhibit significant antiviral effects against different IAV subtypes both in vitro and in vivo. G-rk1 specifically blocks IAV binding to sialic acid and interacts with HA1, making it a potential approach for preventing and treating IAV infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Paolo Governa, Fabrizio Manetti
Summary: The current treatment for HIV-1 infection is not curative and leads to non-compliance and drug resistance. To achieve a cure, new anti-HIV-1 drugs should be developed and viral reservoirs within host cells should be depleted.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)