Purpose Of Review: Even in the era of modern HAART, antiretroviral (ARV) failure and emergence of drug resistance is still a problem worldwide. New classes with different mechanisms of action are needed to overcome this challenge. After the integrase inhibitors were launched, more than a decade ago, no new classes were added to the ARV armamentarium.
Recent Findings: Fostemsavir (FTR) is an attachment inhibitor, active regardless of viral tropism, without cross-resistance to any of the existing ARV compounds. A phase 3 study showed a reduction in plasma viral RNA of 1.21-1.73 log10 copies/ml from baseline after 8 days of functional monotherapy; at 48 weeks, up to 82% of patients treated with FTR and an optimized background ARV regimen achieved virological suppression below 50 copies/ml.
Summary: FTR is an investigational HIV drug with a novel mechanism of action that demonstrates virologic activity in HIV-infected treatment-experienced individuals.
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http://dx.doi.org/10.1097/COH.0000000000000469 | DOI Listing |
J Virol
January 2025
Department of Infectious Diseases, Center of Infectious Diseases and Pathogen Biology, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University, Changchun, Jilin, China.
Unlabelled: Platelet factor 4 (PF4) has been shown to regulate several viral infections. Our previous study demonstrated that PF4 inhibits the entry of enterovirus A 71 (EV71) and coxsackievirus A16 (CA16), which cause hand, foot, and mouth disease (HFMD). In this study, we report that PF4 also inhibits the circulating HFMD pathogen coxsackievirus A6 (CA6) and the re-emerging enterovirus D68 (EVD68).
View Article and Find Full Text PDFViruses
November 2024
Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA.
The host enzyme heparanase (HPSE) facilitates the release of herpes simplex virus type 2 (HSV-2) from target cells by cleaving the viral attachment receptor heparan sulfate (HS) from infected cell surfaces. HPSE 2, an isoform of HPSE, binds to but does not possess the enzymatic activity needed to cleave cell surface HS. Our study demonstrates that HSV-2 infection significantly elevates HPSE 2 protein levels, impacting two distinct stages of viral replication.
View Article and Find Full Text PDFPharmaceutics
December 2024
Department of Chemical Engineering, Biotechnology and Materials, Ariel University, Ariel 40700, Israel.
Here, we report on the synthesis and biological evaluation of a novel peptide-drug conjugate, P6-SN38, which consists of the EGFR-specific short cyclic peptide, P6, and the Topo I inhibitor SN38, which is a bioactive metabolite of the anticancer drug irinotecan. SN38 is attached to the peptide at position 20 of the E ring's tertiary hydroxyl group via a mono-succinate linker. The developed peptide-drug conjugate (PDC) exhibited sub-micromolar anticancer activity on EGFR-positive (EGFR+) cell lines but no effect on EGFR-negative (EGFR-) cells.
View Article and Find Full Text PDFPharmaceutics
December 2024
National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy.
Background/objectives: KRT23 was recently discovered as an epithelial-specific intermediate filament protein in the type I keratin family. Many studies have underlined keratin's involvement in several biological processes as well as in the pathogenesis of different diseases. Specifically, KRT23 was reported to affect the structural integrity of epithelial cells and to trigger cellular signaling leading to the onset of cancer.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Faculty of Chemical Engineering and Technology, Cracow University of Technology, Warszawska 24, 31-155 Kraków, Poland.
Tyrosinase is a key enzyme responsible for the formation of melanin (a natural skin pigment with ultraviolet-protection properties). However, some people experience melanin overproduction, so new, safe, and biocompatible enzyme inhibitors are sought. New tripeptide tyrosinase inhibitors were developed using molecular modeling.
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