Human papillomaviruses (HPVs) are oncogenic viruses that cause numerous different cancers as well as benign lesions in the epithelia. To date, there is no effective cure for an ongoing HPV infection. Here, we describe the generation process of a platform for the development of anti-HPV drugs. This system consists of engineered full-length HPV genomes that express reporter genes for evaluation of the viral copy number in all three HPV replication stages. We demonstrate the usefulness of this system by conducting high-throughput screens to identify novel high-risk HPV-specific inhibitors. At least five of the inhibitors block the function of Tdp1 and PARP1, which have been identified as essential cellular proteins for HPV replication and promising candidates for the development of antivirals against HPV and possibly against HPV-related cancers.
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http://dx.doi.org/10.1371/journal.ppat.1006168 | DOI Listing |
Viruses
December 2024
Laboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani" (IRCCS), 00149 Rome, Italy.
Persistence is a strategy used by many viruses to evade eradication by the immune system, ensuring their permanence and transmission within the host and optimizing viral fitness. During persistence, viruses can trigger various phenomena, including target organ damage, mainly due to an inflammatory state induced by infection, as well as cell proliferation and/or immortalization. In addition to immune evasion and chronic inflammation, factors contributing to viral persistence include low-level viral replication, the accumulation of viral mutants, and, most importantly, maintenance of the viral genome and reliance on viral oncoprotein production.
View Article and Find Full Text PDFViruses
December 2024
Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine.
Metformin, a widely used antidiabetic medication, has emerged as a promising broad-spectrum antiviral agent due to its ability to modulate cellular pathways essential for viral replication. By activating AMPK, metformin depletes cellular energy reserves that viruses rely on, effectively limiting the replication of pathogens such as influenza, HIV, SARS-CoV-2, HBV, and HCV. Its role in inhibiting the mTOR pathway, crucial for viral protein synthesis and reactivation, is particularly significant in managing infections caused by HIV, CMV, and EBV.
View Article and Find Full Text PDFJ Med Virol
January 2025
Department of Dermatology, First Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.
Human papillomavirus (HPV) infections are prevalent skin infectious diseases. While there are no specific anti-HPV drugs available, understanding the viral mechanisms could lead to novel therapeutic strategies. Verruca vulgaris, a common HPV infection, is frequently encountered in dermatological clinics.
View Article and Find Full Text PDFJ Ethnopharmacol
December 2024
MecNano Technologies, Cube Incubation, Teknopark Istanbul, Istanbul, 34906, Türkiye; Department of Pharmacology, Faculty of Pharmacy, Istanbul Kent University, Istanbul, 34406, Türkiye; UCL Division of Surgery and Interventional Sciences, Rowland Hill Street, NW3 2PF, London, UK; Art de Huile, Teknopol Istanbul, Istanbul, 34930, Türkiye; Biomedical Engineering Department, University of Aveiro, Aveiro, 3810-193, Portugal. Electronic address:
Ethnopharmacological Relevance: Clove is used in Indian and Chinese traditional medicine for viral diseases. Palmarosa essential oils have been traditionally used in India and Southeast Asia since ancient times and have made considerable use of them. In New Caledonia, niaouli oil is used in aromatherapy and pharmaceutical formulations to treat pain and viral diseases.
View Article and Find Full Text PDFCancer Control
December 2024
Department of Pathology and Microbiology, School of Medicine, University of Zambia, Lusaka, Zambia.
Background: Despite Zambia implementing the World Health Organisation's (WHO) tri-pillar cervical cancer prevention goals 90-70-90 Prevent, Screen, and Treat, cervical cancer claims 2000 lives annually and reigns as the most common cancer among women, especially those living with HIV (WLHIV). Our study describes the national uptake of screening and treatment from the ZAMPHIA 2021 survey.
Methods: Utilising a two-stage cluster sampling approach, the study included participants aged 15 years and older across Zambia's ten provinces.
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