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, Multidisciplinary
Jordan M. Mattheisen, Chris Limberakis, Roger B. Ruggeri, Matthew S. Dowling, Christopher W. am Ende, Emilie Ceraudo, Thomas Huber, Christopher L. McClendon, Thomas P. Sakmar
Summary: We developed a strategy to covalently tether drug fragments adjacent to allosteric sites in GPCRs to enhance their potency and enable fragment-based drug screening in cell-based systems.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Public, Environmental & Occupational Health
Yenisleidys Martinez-Montesinos, Vivian Kouri-Cordella, Lissette Perez-Santos, Rui Han, Yanet Pintos-Saavedra, Yoan Aleman-Campos, Yudira Soto-Brito, Yoanna Banos-Morales, Yaniris Caturla-Fernandez
Summary: The study found an association between CRF19_cpx and X4 and R5X4 tropic viruses. There is wide diversity in V3 sequences among different HIV-1 subtypes circulating in Cuba.
Article
Biochemistry & Molecular Biology
Anju Krishnan Anitha, Pratibha Narayanan, Neethu Ajayakumar, Krishnankutty Chandrika Sivakumar, Kesavakurup Santhosh Kumar
Summary: This study designed and generated peptide ligands targeting CCR5, which showed significant CCR5 specificity and did not mediate migration of responsive cells.
JOURNAL OF BIOCHEMISTRY
(2022)
Article
Virology
Celien Jacquemard, Florian Koensgen, Philippe Colin, Bernard Lagane, Esther Kellenberger
Summary: Research shows that different variants of HIV-1 gp120 binding to CCR5 can result in changes in receptor conformation, including reshaping of extracellular loops 2 and 3, affecting accessibility to the transmembrane binding cavity, and positioning movements in different protein regions.
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
Virology
Massimiliano Secchi, Luca Vangelista
Summary: The fusion of potent CCR5 antagonist CCL5 5p12 5m with gp41-targeted fusion inhibitor C37 resulted in a protein design with potential therapeutic effects against HIV-1 infection.
Article
Virology
Saumya Anang, Shijian Zhang, Christopher Fritschi, Ta-Jung Chiu, Derek Yang, Amos B. Smith, Navid Madani, Joseph Sodroski
Summary: CD4-mimetic compounds (CD4mcs) can inhibit the entry of HIV-1 into host cells. Changes distant from the binding pocket can influence the susceptibility of natural HIV-1 strains to the antiviral effects of multiple CD4mcs.
JOURNAL OF VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Christopher J. Fritschi, Saumya Anang, Zhen Gong, Mohammadjavad Mohammadi, Jonathan Richard, Catherine Bourassa, Kenny T. Severino, Hannah Richter, Derek Yang, Hung -Ching Chen, Ta-Jung Chiu, Michael S. Seaman, Navid Madani, Cameron Abrams, Andres Finzi, Wayne A. Hendrickson, Joseph G. Sodroski, Amos B. Smith
Summary: Binding of HIV-1 to host cell receptors CD4 and CCR5/CXCR4 causes conformational changes in the viral envelope protein, promoting virus entry. CD4-mimetic compounds (CD4mcs) are small molecules that induce inactivating conformational changes in the viral envelope, making it susceptible to neutralization and ADCC. Novel CD4mcs based on an indoline scaffold demonstrate increased potency and breadth against HIV-1 variants, making them potential candidates for antiviral therapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Multidisciplinary Sciences
Cecile Riviere-Cazaux, Jessica Cornell, Yang Shen, Miou Zhou
Summary: This review summarizes the mechanistic role of CCR5 in HIV-associated cognitive deficits, as well as the research outcomes of using CCR5 antagonists to treat cognitive impairments.
Article
Biochemistry & Molecular Biology
Jimin Yoon, Emmanuel E. Nekongo, Jessica E. Patrick, Tiffani Hui, Angela M. Phillips, Anna I. Ponomarenko, Samuel J. Hendel, Rebecca M. Sebastian, Yu Meng Zhang, Vincent L. Butty, C. Brandon Ogbunugafor, Yu-Shan Lin, Matthew D. Shoulders
Summary: This study investigates the impact of proteostasis networks on the sequence space accessible to HIV-1 envelope protein. The upregulation of the unfolded protein response is found to globally reduce the mutational tolerance of the envelope protein, while specific regions targeted by broadly neutralizing antibodies exhibit enhanced mutational tolerance. These findings highlight the importance of proteostasis networks in shaping the mutational tolerance of client proteins and have implications for HIV adaptation.
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.
Review
Microbiology
Jason Segura, Biao He, Joanna Ireland, Zhongcheng Zou, Thomas Shen, Gwynne Roth, Peter D. Sun
Summary: Viral glycans play an important role in HIV entry, facilitating viral adhesion and entry by interacting with L-selectin. Shedding of L-selectin from infected CD4 T lymphocytes significantly reduces HIV viral release, causing aggregation of diminutive virus-like particles.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Physical
Jinbang Zhang, Zhengyang Li, Jiaxin Li, Hui Li, Junwei Che, Te Zhao, Pengfei Zou, Jingwan Han, Yang Yang, Meiyan Yang, Yuli Wang, Wei Gong, Haihua Xiao, Zhiping Li, Lin Li, Chunsheng Gao
Summary: A glycoprotein 120 (gp120)-targeting polypeptide UM15 reinforced lymphocyte-mimicking nanotrap was constructed to improve the HIV-1 inhibiting efficacy. The constructed nanotraps exhibited escaping ability from uptake of the mononuclear phagocyte system and improved binding ability with gp120 proteins. These nanotraps neutralized all tested HIV-1 pseudo-typed viruses and inhibited both X4-tropic and R5-tropic HIV-1.
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)
Review
Chemistry, Medicinal
Robert A. Pearlstein, K. Andrew MacCannell, Gul Erdemli, Sarita Yeola, Gabriel Helmlinger, Qi-Ying Hu, Ramy Farid, William Egan, Steven Whitebread, Clayton Springer, Jeremy Beck, Hao-Ran Wang, Mateusz Maciejewski, Laszlo Urban, Jose S. Duca
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Bradley Sherborne, Veerabahu Shanmugasundaram, Alan C. Cheng, Clara D. Christ, Renee L. DesJarlais, Jose S. Duca, Richard A. Lewis, Deborah A. Loughney, Eric S. Manas, Georgia B. McGaughey, Catherine E. Peishoff, Herman van Vlijmen
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2016)
Article
Chemistry, Multidisciplinary
Callum J. Dickson, Viktor Hornak, Robert A. Pearlstein, Jose S. Duca
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2017)
Article
Chemistry, Medicinal
Xin Chen, John Giraldes, Elizabeth R. Sprague, Subarna Shakya, Zhuoliang Chen, Yaping Wang, Carol Joud, Simon Mathieu, Christine Hiu-Tung Chen, Christopher Straub, Jose Duca, Kristen Hurov, Yanqiu Yuan, Wenlin Shao, B. Barry Toure
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Callum J. Dickson, Viktor Hornak, Dallas Bednarczyk, Jose S. Duca
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Chemistry, Medicinal
Jose Jimenez, Davide Sabbadin, Alberto Cuzzolin, Gerard Martinez-Rosell, Jacob Gora, John Manchester, Jose Duca, Gianni De Fabritiis
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Biochemistry & Molecular Biology
Keith Jendza, Mitsunori Kato, Michael Salcius, Honnappa Srinivas, Andrea De Erkenez, Anh Nguyen, Doug McLaughlin, Celine Be, Christian Wiesmann, Jason Murphy, Philippe Bolduc, Muneto Mogi, Jose Duca, Abdel Namil, Michael Capparelli, Veronique Darsigny, Erik Meredith, Ritesh Tichkule, Luciana Ferrara, Jessica Heyder, Fang Liu, Patricia A. Horton, Michael J. Romanowski, Markus Schirle, Nello Mainolfi, Karen Anderson, Gregory A. Michaud
NATURE CHEMICAL BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Lieyang Chen, Anthony Cruz, Steven Ramsey, Callum J. Dickson, Jose S. Duca, Viktor Hornak, David R. Koes, Tom Kurtzman
Article
Biochemistry & Molecular Biology
Kellyann N. Jones-Jamtgaard, Ann L. Wozniak, Hiroshi Koga, Robert Ralston, Steven A. Weinman
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Virology
Dandan Liu, Philip R. Tedbury, Shuiyun Lan, Andrew D. Huber, Maritza N. Puray-Chavez, Juan Ji, Eleftherios Michailidis, Mohsan Saeed, Tanyaradzwa P. Ndongwe, Leda C. Bassit, Raymond F. Schinazi, Robert Ralston, Charles M. Rice, Stefan G. Sarafianos
Article
Chemistry, Medicinal
Callum J. Dickson, Camilo Velez-Vega, Jose S. Duca
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2020)
Review
Biotechnology & Applied Microbiology
Petra Schneider, W. Patrick Walters, Alleyn T. Plowright, Norman Sieroka, Jennifer Listgarten, Robert A. Goodnow, Jasmin Fisher, Johanna M. Jansen, Jose S. Duca, Thomas S. Rush, Matthias Zentgraf, John Edward Hill, Elizabeth Krutoholow, Matthias Kohler, Jeff Blaney, Kimito Funatsu, Chris Luebkemann, Gisbert Schneider
NATURE REVIEWS DRUG DISCOVERY
(2020)
Article
Chemistry, Physical
Christos Lamprakis, Ioannis Andreadelis, John Manchester, Camilo Velez-Vega, Jose S. Duca, Zoe Cournia
Summary: The study suggests that Martini 2.2P overestimates the free energy of association for proteins, while Martini 3 performs better in describing the association of membrane proteins. Near-native dimer complexes are identified as minima in the free energy surface, although not always as the lowest minima.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Multidisciplinary
Anna Pavlova, Diane L. Lynch, Isabella Daidone, Laura Zanetti-Polzi, Micholas Dean Smith, Chris Chipot, Daniel W. Kneller, Andrey Kovalevsky, Leighton Coates, Andrei A. Golosov, Callum J. Dickson, Camilo Velez-Vega, Jose S. Duca, Josh V. Vermaas, Yui Tik Pang, Atanu Acharya, Jerry M. Parks, Jeremy C. Smith, James C. Gumbart
Summary: The main protease of SARS-CoV-2 is a promising target for antiviral therapeutics, crucial in the viral life cycle. The stability of its structure is highly sensitive to the protonation states of key residues, impacting drug design efforts.
Review
Chemistry, Medicinal
Robert A. Pearlstein, Daniel J. J. McKay, Viktor Hornak, Callum Dickson, Andrei Golosov, Tyler Harrison, Camilo Velez-Vega, Jose Duca
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2017)
Article
Virology
Naiqing Xu, Xinen Tang, Xin Wang, Miao Cai, Xiaowen Liu, Xiaolong Lu, Shunlin Hu, Min Gu, Jiao Hu, Ruyi Gao, Kaituo Liu, Yu Chen, Xiufan Liu, Xiaoquan Wang
Summary: This study found that the H9N2 subtype avian influenza virus has a high airborne transmissibility, while the H7N9 virus does not. The Hemagglutinin protein of the H9N2 virus was found to play a key role in replication, stability, and airborne transmission.
Article
Virology
Samar S. Ewies, Sabry M. Tamam, Ahmed S. Abdel-Moneim, Sherin R. Rouby
Summary: Contagious ecthyma (CE) is a highly contagious viral disease of sheep and goats worldwide. The study provided a clinical description of CE and screened for genetic variation in the B2L gene. Infected sheep exhibited anorexia and oral lesions, while inoculated chicken embryos showed pock lesions. The B2L gene was successfully amplified and found to be highly conserved.
Article
Virology
Yigal Farnoushi, Dan Heller, Avishai Lublin
Summary: In recent years, new variants of avian reovirus (ARV) have caused a variety of symptoms in chickens worldwide, including viral arthritis/tenosynovitis. This study analyzed emerging ARV variants in Israel and found significant genetic diversity. Most ARV isolates in Israel belonged to genotypic cluster 5 (GC5). The study suggests that Israel has not experienced the emergence of new ARV variants since the introduction of the live vaccine (ISR-7585), but ongoing monitoring is needed due to the continuous emergence of ARV variants.
Article
Virology
Shigeru Tajima, Michiyo Kataoka, Yuki Takamatsu, Hideki Ebihara, Chang-Kweng Lim
Summary: Yokose virus (YOKV), a bat-associated flavivirus, was found to replicate at a slower rate in mosquito cells compared to other mosquito-borne flaviviruses. Specific nucleotide mutations in the virus were identified to enhance its proliferation ability in mosquito cells.
Article
Virology
Alejandra Borjabad, Baojun Dong, Wei Chao, David J. Volsky, Mary Jane Potash
Summary: This study investigated HIV brain disease using a mouse model, and found that poly I:C can reverse associated cognitive impairment and reduce virus burden. The results also revealed transcriptional changes related to neuronal function and innate immune responses.
Article
Virology
Ching-Hung Lin, Feng-Cheng Hsieh, Meilin Wang, Chieh Hsu, Hsuan-Wei Hsu, Chun-Chun Yang, Cheng-Yao Yang, Hung-Yi Wu
Summary: This study demonstrates that the synthesis of coronavirus subgenomic mRNA is not solely determined by the sequence homology between the leader TRS and TRS-B, but also by the disassociation of the coronavirus polymerase from the viral genome. This finding provides a new insight into the transcription mechanism of coronaviruses.
Article
Virology
Nicholas S. Kron, Benjamin W. Neuman, Sathish Kumar, Patricia L. Blackwelder, Dayana Vidal, Delphina Z. Walker-Phelan, Patrick D. I. Gibbs, Lynne A. Fieber, Michael C. Schmale
Summary: Two recent studies documented the genome of a novel virus in marine animals, finding that the virus is widespread in apparently healthy animals but not highly expressed in neurons. The studies also identified viral replication factories and high levels of defective genomes in chronically infected animals.
Article
Virology
Andrew M. Ramey, Laura C. Scott, Christina A. Ahlstrom, Evan J. Buck, Alison R. Williams, Mia Kim Torchetti, David E. Stallknecht, Rebecca L. Poulson
Summary: We successfully detected and characterized highly pathogenic avian influenza viruses in hunter-harvested wild waterfowl samples from western Alaska. Genomic analysis revealed three independent viral introductions into Alaska. Our findings demonstrate the utility and potential limitations of using molecular processing approaches directly on original swab samples for viral research and monitoring.
Article
Virology
Ting Gong, Dongdong Wu, Yongzhi Feng, Xing Liu, Qi Gao, Xiaoyu Zheng, Zebu Song, Heng Wang, Guihong Zhang, Lang Gong
Summary: This study discovered that quercetin can inhibit PEDV replication both in vivo and in vitro, and alleviate the clinical symptoms and intestinal injury caused by the virus. This provides a new direction for the development of PED antiviral drugs.
Article
Virology
Min Zhu, Hao Zeng, Jianqiao He, Yaohui Zhu, Pingping Wang, Jianing Guo, Jinfan Guo, Huabo Zhou, Yifeng Qin, Kang Ouyang, Zuzhang Wei, Weijian Huang, Ying Chen
Summary: The reassortment between avian H9N2 and Eurasian avian-like (EA) H1N1 viruses may have potentially changed from avian-to-mammals adaptation. This study found that the introduction of EA H1N1 internal genes into H9N2 virus restored the replication capability and resulted in extreme virulence in some cases. This raises new concerns for public health due to the possible coexistence of H9N2 and EA H1N1 viruses in dogs.