Article
Biochemistry & Molecular Biology
Takuya Kobayakawa, Masaru Yokoyama, Kohei Tsuji, Masayuki Fujino, Masaki Kurakami, Sayaka Boku, Miyuki Nakayama, Moemi Kaneko, Nami Ohashi, Osamu Kotani, Tsutomu Murakami, Hironori Sato, Hirokazu Tamamura
Summary: A small molecule designed to mimic hydrophobic interactions between HIV-1 capsid proteins has shown significant anti-HIV-1 activity. Structure activity relationship (SAR) studies of its derivatives provide valuable information for the design and development of novel anti-HIV agents targeting the capsid protein. This new drug has the potential to be an effective treatment for HIV in the future.
Article
Multidisciplinary Sciences
James C. V. Stacey, Aaron Tan, John M. Lu, Leo C. James, Robert A. Dick, John A. G. Briggs
Summary: Using single-particle cryoEM, researchers have determined the structure of the mature HIV-1 CA pentamer and hexamer from conical CA-IP6 polyhedra. Comparison of these structures revealed that the conical HIV-1 capsid has different host-protein binding properties at different positions on its surface, which may facilitate cell entry and represent an evolutionary advantage of conical morphology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Manish Gupta, Alexander J. Pak, Gregory A. Voth
Summary: Researchers use molecular dynamics simulations to reveal the molecular mechanism of HIV-1 capsid formation, including the role of IP6. This study shows that IP6 initially promotes curvature generation by trapping pentameric defects and shifts the assembly behavior towards kinetically favored outcomes. Additionally, IP6 can stabilize metastable capsid intermediates and induce structural pleomorphism in mature capsids.
Article
Chemistry, Multidisciplinary
Takuya Kobayakawa, Masaru Yokoyama, Kohei Tsuji, Masayuki Fujino, Masaki Kurakami, Takato Onishi, Sayaka Boku, Takahiro Ishii, Yutaro Miura, Kouki Shinohara, Yuki Kishihara, Nami Ohashi, Osamu Kotani, Tsutomu Murakami, Hironori Sato, Hirokazu Tamamura
Summary: The HIV-1 capsid is crucial for viral replication and represents a potential target for antiviral drugs. A small molecule designed to mimic the interaction between CA proteins has shown significant anti-HIV-1 activity. In this study, molecules with different structures based on this small molecule were synthesized and found to have significant anti-HIV activity, with advantages over previous compounds.
Review
Microbiology
Sooin Jang, Alan N. Engelman
Summary: The HIV-1 capsid interacts with a variety of host factors during cell entry and nuclear transport, and the timing and location of capsid uncoating are still debated. Recent research suggests that the capsid remains largely intact during nuclear import and may require structural remodeling for nuclear pore complex traversal. Host factors like CPSF6 bind to the capsid using peptide sequences located within prion-like domains. Understanding capsid-host interactions is important for studying HIV-1 infection and has led to the development of drugs like lenacapavir that target the same capsid binding pocket as host factors.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2023)
Article
Virology
Nicholas T. N. Lo, Susan Z. Roodsari, Nicole L. Tin, Marcus P. Wong, Scott B. Biering, Eva Harris
Summary: Flavivirus NS1 is a viral protein that is secreted into the bloodstream during an infection. It plays a role in severe dengue pathology such as endothelial dysfunction and vascular leak. In this study, we investigated the molecular determinants that allow some flavivirus NS1 proteins to bind to specific endothelial cells and cause vascular leak in a mouse model. We found that the wing domain of NS1 is a primary determinant for endothelial dysfunction and vascular leak, and narrowed down the contributing amino acid residues to a three-residue motif within the wing domain.
JOURNAL OF VIROLOGY
(2022)
Article
Medicine, General & Internal
Sorana Segal-Maurer, Edwin DeJesus, Hans-Jurgen Stellbrink, Antonella Castagna, Gary J. Richmond, Gary I. Sinclair, Krittaecho Siripassorn, Peter J. Ruane, Mezgebe Berhe, Hui Wang, Nicolas A. Margot, Hadas Dvory-Sobol, Robert H. Hyland, Diana M. Brainard, Martin S. Rhee, Jared M. Baeten, Jean-Michel Molina
Summary: Patients with multidrug-resistant HIV-1 infection showed greater reduction in viral load when treated with lenacapavir compared to placebo.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Infectious Diseases
Allison M. Hitchcock, Wesley D. Kufel, Keri A. Mastro Dwyer, Eric F. Sidman
Summary: Lenacapavir is a novel HIV-1 treatment option for patients with multidrug-resistant (MDR) HIV-1 infection. It has a favorable pharmacokinetic profile and has shown good tolerability and efficacy in clinical trials.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)
Article
Microbiology
Chunfu Wang, Haichang Huang, Kirsten Mallon, Lourdes Valera, Kyle Parcella, Mark I. Cockett, John F. Kadow, Eric P. Gillis, Mark Krystal, Robert A. Fridell
Summary: GSK878 is a potent inhibitor of HIV-1 that binds to the CA hexamer. It shows high efficacy against HIV-1 and variants with diverse CA sequences. Mechanism studies reveal that GSK878 blocks early and late steps of HIV-1 replication, primarily through altered stability of the HIV-1 CA core.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Paloma Troyano-Hernaez, Roberto Reinosa, Africa Holguin
Summary: The HIV-1 p24 protein plays a crucial role in the viral replication cycle and is important for vaccine design and antiretroviral drug development. This study analyzed the diversity of p24 among different HIV-1 variants and within its secondary structure. The results showed variations in conservation among different variants and secondary structure types, with overall high conservation. These findings provide valuable information for understanding the variability of p24 and developing effective strategies against HIV-1.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Chemistry, Analytical
Derrick Lau, James C. Walsh, Claire F. Dickson, Andrew Tuckwell, Jeffrey H. Stear, Dominic J. B. Hunter, Akshay Bhumkar, Vaibhav Shah, Stuart G. Turville, Emma Sierecki, Yann Gambin, Till Bocking, David A. Jacques
Summary: The study developed a fluorescence analysis method using HIV capsid as bait to screen for fluorescence-labeled binding molecules. By using a scanning stage, rapid detection was achieved without compromising sensitivity, providing a new approach for screening potential interactors.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sunnie M. Yoh, Joao Mamede, Derrick Lau, Narae Ahn, Maria T. Sanchez-Aparicio, Joshua Temple, Andrew Tuckwell, Nina Fuchs, Gianguido C. Cianci, Laura Riva, Heather Curry, Xin Yin, Stephanie Gambut, Lacy M. Simons, Judd F. Hultquist, Renate Koenig, Yong Xiong, Adolfo Garcia-Sastre, Till Bocking, Thomas J. Hope, Sumit K. Chanda
Summary: This study reveals a two-factor authentication strategy by the innate surveillance machinery to selectively respond to low concentration of HIV-1 DNA, using the decoration of PQBP1 on the viral capsid and the recruitment of cGAS.
Article
Multidisciplinary Sciences
Guangai Xue, Hyun Jae Yu, Cindy Buffone, Szu-Wei Huang, KyeongEun Lee, Shih Lin Goh, Anna T. T. Gres, Mehmet Hakan Guney, Stefan G. G. Sarafianos, Jeremy Luban, Felipe Diaz-Griffero, Vineet N. N. KewalRamani
Summary: The entry of HIV-1 into the nucleus is regulated by the interaction between the viral capsid protein CA and nuclear pore complex proteins Nup35 and POM121. This interaction is also influenced by soluble host factors such as Cyclophilin A. These findings highlight the role of CA as a macromolecular nuclear transport receptor and provide insights into the mechanism of HIV-1 nuclear invasion.
NATURE COMMUNICATIONS
(2023)
Review
Virology
Anabel Guedan, Eve R. Caroe, Genevieve C. R. Barr, Kate N. Bishop
Summary: HIV-1 infection involves traversing the nuclear envelope to access the host cell chromatin for integration. The uncoating process, which occurs prior to integration, is crucial for viral infectivity. The relationship between uncoating and nuclear entry is a topic of current debate in the field.
Article
Biochemistry & Molecular Biology
Sergi Chumillas, Saurabh Loharch, Manuela Beltran, Mateusz P. Szewczyk, Silvia Bernal, Maria C. Puertas, Javier Martinez-Picado, Jose Alcami, Luis M. Bedoya, Vicente Marchan, Jose Gallego
Summary: This study explored the optimization of the antiretroviral properties of benfluron and found that both the benzo[c] and cyclopentanone components are essential for its activity. The results provide insights for the design of new anti-HIV agents targeting the inhibition of Rev function.
Article
Biochemistry & Molecular Biology
Jason D. Fernandes, Tyler B. Faust, Nicolas B. Strauli, Cynthia Smith, David C. Crosby, Robert L. Nakamura, Ryan D. Hernandez, Alan D. Frankel
Review
Cell Biology
Jason D. Fernandes, David S. Booth, Alan D. Frankel
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2016)
Article
Biochemical Research Methods
Stefanie Jaeger, Natali Gulbahce, Peter Cimermancic, Joshua Kane, Nanhai He, Seemay Chou, Ivan D'Orso, Jason Fernandes, Gwendolyn Jang, Alan D. Frankel, Tom Alber, Qiang Zhou, Nevan J. Krogan
Article
Multidisciplinary Sciences
Stefanie Jaeger, Peter Cimermancic, Natali Gulbahce, Jeffrey R. Johnson, Kathryn E. McGovern, Starlynn C. Clarke, Michael Shales, Gaelle Mercenne, Lars Pache, Kathy Li, Hilda Hernandez, Gwendolyn M. Jang, Shoshannah L. Roth, Eyal Akiva, John Marlett, Melanie Stephens, Ivan D'Orso, Jason Fernandes, Marie Fahey, Cathal Mahon, Anthony J. O'Donoghue, Aleksandar Todorovic, John H. Morris, David A. Maltby, Tom Alber, Gerard Cagney, Frederic D. Bushman, John A. Young, Sumit K. Chanda, Wesley I. Sundquist, Tanja Kortemme, Ryan D. Hernandez, Charles S. Craik, Alma Burlingame, Andrej Sali, Alan D. Frankel, Nevan J. Krogan
Article
Biochemistry & Molecular Biology
Jason D. Fernandes, Bhargavi Jayaraman, Alan D. Frankel
Article
Multidisciplinary Sciences
Bhargavi Jayaraman, Jason D. Fernandes, Shumin Yang, Cynthia Smith, Alan D. Frankel
SCIENTIFIC REPORTS
(2019)
Article
Multidisciplinary Sciences
Mariam Okhovat, Kimberly A. Nevonen, Brett A. Davis, Pryce Michener, Samantha Ward, Mark Milhaven, Lana Harshman, Ajuni Sohota, Jason D. Fernandes, Sofie R. Salama, Rachel J. O'Neil, Nadav Ahituv, Krishna R. Veeramah, Lucia Carbone
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biology
Jason D. Fernandes, Sarvenaz Sarabipour, Christopher T. Smith, Natalie M. Niemi, Nafisa M. Jadavji, Ariangela J. Kozik, Alex S. Holehouse, Vikas Pejaver, Orsolya Symmons, Alexandre W. Bisson Filho, Amanda Haage
Article
Genetics & Heredity
Yatish Turakhia, Nicola De Maio, Bryan Thornlow, Landen Gozashti, Robert Lanfear, Conor R. Walker, Angie S. Hinrichs, Jason D. Fernandes, Rui Borges, Greg Slodkowicz, Lukas Weilguny, David Haussler, Nick Goldman, Russell Corbett-Detig
Article
Biology
Maliheh Safari, Bhargavi Jayaraman, Shumin Yang, Cynthia Smith, Jason D. Fernandes, Alan D. Frankel, Karla Kirkegaard
Summary: Overlapping coding regions can balance selective forces between multiple genes, even when both protein products are structured over the same sequence. This study in HIV-1 found that even in an overlapped region, functional segregation occurs as each protein spaces its functional residues in a way that allows important functional residues to be encoded on a different helix.
Article
Multidisciplinary Sciences
Wesley C. Warren, R. Alan Harris, Marina Haukness, Ian T. Fiddes, Shwetha C. Murali, Jason Fernandes, Philip C. Dishuck, Jessica M. Storer, Muthuswamy Raveendran, LaDeana W. Hillier, David Porubsky, Yafei Mao, David Gordon, Mitchell R. Vollger, Alexandra P. Lewis, Katherine M. Munson, Elizabeth DeVogelaere, Joel Armstrong, Mark Diekhans, Jerilyn A. Walker, Chad Tomlinson, Tina A. Graves-Lindsay, Milinn Kremitzki, Sofie R. Salama, Peter A. Audano, Merly Escalona, Nicholas W. Maurer, Francesca Antonacci, Ludovica Mercuri, Flavia A. M. Maggiolini, Claudia Rita Catacchio, Jason G. Underwood, David H. O'Connor, Ashley D. Sanders, Jan O. Korbel, Betsy Ferguson, H. Michael Kubisch, Louis Picker, Ned H. Kalin, Douglas Rosene, Jon Levine, David H. Abbott, Stanton B. Gray, Mar M. Sanchez, Zsofia A. Kovacs-Balint, Joseph W. Kemnitz, Sara M. Thomasy, Jeffrey A. Roberts, Erin L. Kinnally, John P. Capitanio, J. H. Pate Skene, Michael Platt, Shelley A. Cole, Richard E. Green, Mario Ventura, Roger W. Wiseman, Benedict Paten, Mark A. Batzer, Jeffrey Rogers, Evan E. Eichler
Article
Biotechnology & Applied Microbiology
Jana Ebler, Marina Haukness, Trevor Pesout, Tobias Marschall, Benedict Paten