ArticlebioRxiv : the preprint server for biology2025
Structural, biophysical, and virological mechanistic characterization of HIV-1 capsid-targeting antivirals.
Karen A Kirby, William M McFadden, Lei Wang, Haijuan Du, Huanchun Zhang, Andres Emanuelli Castaner, Zachary C Lorson, Arvin Nafisi, Charlotte Luchsinger, Atsuko Hachiya and 10 more
Abstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registryThe trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
3 · Its place in the literatureWho cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
4 · The recordCorrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what moneyAuthors and funding
20 authors.
Karen A KirbyCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.ORCID 0000-0003-2468-4796 William M McFaddenCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.ORCID 0000-0001-6911-2172 Lei WangCenter for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN.
Haijuan DuCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.
Huanchun ZhangCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.
Andres Emanuelli CastanerCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.ORCID 0009-0005-1275-9684 Zachary C LorsonCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.ORCID 0009-0002-1404-9086 Arvin NafisiInstitute of Molecular Biophysics and Department of Biological Sciences, Florida State University, Tallahassee, FL.
Charlotte LuchsingerDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY.ORCID 0000-0001-6775-7778 Atsuko HachiyaClinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
Maria E CilentoCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.ORCID 0000-0001-7597-1248 Alexa A SnyderCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.ORCID 0000-0001-9326-343X Shreya M RavichandranCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.ORCID 0009-0007-4960-3194 Xinyong CaiCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.ORCID 0009-0005-0989-2863 Philip R TedburyCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.ORCID 0000-0001-8151-4967 Ashwanth C FrancisInstitute of Molecular Biophysics and Department of Biological Sciences, Florida State University, Tallahassee, FL.ORCID 0000-0002-8663-2038 Gregory B MelikyanDivision of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.
Felipe Diaz-GrifferoDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY.ORCID 0000-0002-7021-6152 Zhengqiang WangCenter for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN.ORCID 0000-0002-1326-5986 Stefan G SarafianosCenter for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.ORCID 0000-0002-5840-154X Funding
Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Ann M Chahroudi, Colleen F Kelley · 2002 to 2026
$74.0MStructural studies of HIV Capsid with host factors and Capsid-targeting antiviralsR01AI120860 · NIAID · UNIVERSITY OF MISSOURI-COLUMBIA · PI Stefan G Sarafianos, Zhengqiang Wang · 2015 to 2026
$6.0MTraining Program in Biochemistry, Cell and Molecular BiologyT32GM135060 · NIGMS · EMORY UNIVERSITY · PI Lawrence H. Boise, ANITA H. CORBETT · 2020 to 2026
$2.8MPhase II SER-CAT Optimization: Acquisition of a next generation area detectorS10RR028976 · NCRR · UNIVERSITY OF GEORGIA · PI WANG, BI-CHENG · 2010 to 2010
$1.5MAcquisition of a High Precision Micro Diffractometer to Support NIH funded Research at SER-CATS10OD027000 · OD · UNIVERSITY OF GEORGIA · PI ROSE, JOHN PATRICK · 2019 to 2019
$600kNovel HIV capsid-targeting antivirals maintain activity against lenacapavir-resistant virusesR21AI189247 · NIAID · EMORY UNIVERSITY · PI Karen A Kirby · 2025 to 2026
$457kAcquition of a microdiffractometer for SER-CATS10RR025528 · NCRR · UNIVERSITY OF GEORGIA · PI ROSE, JOHN PATRICK · 2009 to 2009
$414kCytoskeletal regulation of T cell-APC interactionsR56AI094923 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI HUTTENLOCHER, ANNA · 2012 to 2012
$410kStructural and Biochemical Effects of Capsid-targeting Molecules on HIV-1 Capsid AssemblyF31AI174951 · NIAID · EMORY UNIVERSITY · PI WILLIAM MICHAEL MCFADDEN · 2023 to 2026
$196kMechanisms of HIV-1 Hypersensitivity to IslatravirF31AI172618 · NIAID · EMORY UNIVERSITY · PI SNYDER, ALEXA ANNE · 2022 to 2025
$193kNovel Antivirals Targeting Lenacapavir-Resistant HIVF31AI194923 · NIAID · EMORY UNIVERSITY · PI Shreya Meenakshi Ravichandran · 2025 to 2026
$100kNCRR NIH HHS S10 RR025528NCRR NIH HHS S10 RR028976NIAID NIH HHS F31 AI172618NIAID NIH HHS F31 AI174951NIAID NIH HHS F31 AI194923NIAID NIH HHS P30 AI050409NIAID NIH HHS R01 AI120860NIAID NIH HHS R21 AI189247NIAID NIH HHS R56 AI094923NIGMS NIH HHS T32 GM135060NIH HHS S10 OD027000
6 · The paper itselfAbstract
Due to its significant role in virus replication, the HIV capsid is an attractive antiviral target. This is validated by the recent clinical approval of lenacapavir for both treatment and pre-exposure prophylaxis (PrEP). PF74 is a well-characterized capsid-targeting antiviral that was discontinued in further study due to potency and metabolic issues. We hypothesized that making chemical modifications at certain sites of PF74 could result in capsid-targeting antivirals with improved potency and bioavailability. Our cumulative studies show that making changes at the R1 and R3 positions of PF74 results in compounds with increased antiviral potency, increased stability of wild-type HIV capsid hexamers and virions, tighter binding to wild-type HIV capsid hexamer compared to PF74, and different interactions at the "FG" binding site of capsid compared to PF74. These data provide insights into the design of future capsid-targeting antivirals relevant for clinical use.
Identifiers
PMID41509269
PMCPMC12776547
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390