Alphaviruses are a serious threat to global health and can cause lethal encephalitic or arthritogenic disease in humans and animals. As there are no licensed antivirals, it is critical to improve our understanding of alphavirus interactions with the host cell. Here, we focus on the essential alphavirus protein capsid. While its roles in genome packaging and virus assembly have been wellstudied, much less is known about capsid's interactions with host proteins and their functional relevance for infection. Recently, several new capsid interactor candidates were identified, collectively emphasising the complexity of capsid-host biology. In this review we summarise these novel interactor candidates, highlight capsid's emerging role in immune evasion, and discuss the challenges and opportunities arising from capsid-host interactions.
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http://dx.doi.org/10.1016/j.tim.2024.11.003 | DOI Listing |
Trends Microbiol
December 2024
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address:
J Med Chem
November 2024
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong 250012, PR China.
Based on our proposed "pseudosubstrate envelope" concept, 25 benzothiazole-bearing HIV capsid protein (CA) modulators were designed and synthesized under the guidance of free energy perturbation technology. The most potent compound, , exhibited an EC of 2.69 nM against HIV-1, being 393 times more potent than the positive control PF74.
View Article and Find Full Text PDFAdv Sci (Weinh)
May 2024
National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, 550025, China.
The control of potato virus Y (PVY) induced crop failure is a challengeable issue in agricultural chemistry. Although many anti-PVY agents are designed to focus on the functionally important coat protein (CP) of virus, how these drugs act on CP to inactivate viral pathogenicity, remains largely unknown. Herein, a PVY CP inhibitor -3j (S) is disclosed, which is accessed by developing unusually efficient (up to 99% yield) and chemo-selective (> 99:1 er in most cases) carbene-catalyzed [3+4] cycloaddition reactions.
View Article and Find Full Text PDFJ Med Chem
December 2023
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Jinan, Shandong, PR China.
Optimization of compound 11L led to the identification of novel HIV capsid modulators, quinazolin-4-one-bearing phenylalanine derivatives, displaying potent antiviral activities against both HIV-1 and HIV-2. Notably, derivatives and showed significant improvements, with 2.5-fold over 11L and 7.
View Article and Find Full Text PDFMicrobiol Mol Biol Rev
December 2023
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
The HIV-1 capsid, composed of approximately 1,200 copies of the capsid protein, encases genomic RNA alongside viral nucleocapsid, reverse transcriptase, and integrase proteins. After cell entry, the capsid interacts with a myriad of host factors to traverse the cell cytoplasm, pass through the nuclear pore complex (NPC), and then traffic to chromosomal sites for viral DNA integration. Integration may very well require the dissolution of the capsid, but where and when this uncoating event occurs remains hotly debated.
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