HIV and Viral Hepatitis: Prevention, Treatment and Coinfection

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Biopharmaceuticals".

Deadline for manuscript submissions: 24 June 2024 | Viewed by 1721

Special Issue Editors


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Guest Editor
Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Madrid, Spain
Interests: hepatitis C virus; HIV; infectious diseases; virology; nanomedicine; neutralizing antibody

E-Mail Website
Guest Editor
Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Madrid, Spain
Interests: HIV; hepatitis C; infectious diseases; immunology; virology; genetics; epidemiology; cirrhosis
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Special Issue Information

Dear Colleagues,

Since viral hepatitis and HIV share transmission routes, many HIV-infected individuals are also co-infected with HBV, HCV, and HDV. Hepatitis viruses are a leading cause of morbi-mortality worldwide, leading to cirrhosis, end-stage liver disease, hepatocellular carcinoma, and death. According to the WHO, 1.4 million people die yearly due to viral hepatitis worldwide. Although extraordinary progress has been made in treating hepatitis C, there are still important issues without solving, particularly in treating hepatitis B and D. On the other hand, HIV attacks and weakens the immune system progressively, destroying CD4 cells and leading to AIDS progression. According to the WHO, 37.7 million people living with HIV, and approximately 600,000 died from HIV-related causes. The prevention of HIV infection through antiretroviral therapy is a critical point in combating this infection. The number of drugs to treat HIV-infected patients is large, but none of them has solved the problem of achieving a permanent functional cure, much less the total HIV elimination of the body.

In this Special Issue, we invite contributors to publish their research on discovering drugs with novel mechanisms of action, biomolecules, or novel biological targets to provide very effective tools in treating, preventing, and eradicating these hepatitis viruses and HIV.

Bullet-point topics:

  • Prevention and/or treatment of HIV and HBV, HCV, and HDV
  • Drug discovery and screening: small molecules, biomolecules, natural products
  • Novel anti-HIV, -HBV, HCV, and -HDV inhibitors
  • HIV and hepatitis viruses vaccine development
  • Broadly neutralizing antibodies
  • Drug delivery
  • Microbicides: novel pharmaceutical preparations
  • Nanotechnology
  • In vitro studies
  • Pre- and clinical trials
  • HIV/hepatitis viruses coinfection
  • Coinfection with other sexually transmitted viruses

Dr. Daniel Sepúlveda-Crespo
Dr. Salvador Resino
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • coinfection
  • drug discovery
  • HBV
  • HCV
  • HDV
  • HIV
  • neutralizing antibodies
  • prevention
  • treatment
  • vaccine

Published Papers (1 paper)

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Research

25 pages, 4607 KiB  
Article
HIV-1 Transcription Inhibition Using Small RNA-Binding Molecules
by Pooja Khatkar, Gifty Mensah, Shangbo Ning, Maria Cowen, Yuriy Kim, Anastasia Williams, Fardokht A. Abulwerdi, Yunjie Zhao, Chen Zeng, Stuart F. J. Le Grice and Fatah Kashanchi
Pharmaceuticals 2024, 17(1), 33; https://doi.org/10.3390/ph17010033 - 25 Dec 2023
Viewed by 1120
Abstract
The HIV-1 transactivator protein Tat interacts with the transactivation response element (TAR) at the three-nucleotide UCU bulge to facilitate the recruitment of transcription elongation factor-b (P-TEFb) and induce the transcription of the integrated proviral genome. Therefore, the Tat–TAR interaction, unique to the virus, [...] Read more.
The HIV-1 transactivator protein Tat interacts with the transactivation response element (TAR) at the three-nucleotide UCU bulge to facilitate the recruitment of transcription elongation factor-b (P-TEFb) and induce the transcription of the integrated proviral genome. Therefore, the Tat–TAR interaction, unique to the virus, is a promising target for developing antiviral therapeutics. Currently, there are no FDA-approved drugs against HIV-1 transcription, suggesting the need to develop novel inhibitors that specifically target HIV-1 transcription. We have identified potential candidates that effectively inhibit viral transcription in myeloid and T cells without apparent toxicity. Among these candidates, two molecules showed inhibition of viral protein expression. A molecular docking and simulation approach was used to determine the binding dynamics of these small molecules on TAR RNA in the presence of the P-TEFb complex, which was further validated by a biotinylated RNA pulldown assay. Furthermore, we examined the effect of these molecules on transcription factors, including the SWI/SNF complex (BAF or PBAF), which plays an important role in chromatin remodeling near the transcription start site and hence regulates virus transcription. The top candidates showed significant viral transcription inhibition in primary cells infected with HIV-1 (98.6). Collectively, our study identified potential transcription inhibitors that can potentially complement existing cART drugs to address the current therapeutic gap in current regimens. Additionally, shifting of the TAR RNA loop towards Cyclin T1 upon molecule binding during molecular simulation studies suggested that targeting the TAR loop and Tat-binding UCU bulge together should be an essential feature of TAR-binding molecules/inhibitors to achieve complete viral transcription inhibition. Full article
(This article belongs to the Special Issue HIV and Viral Hepatitis: Prevention, Treatment and Coinfection)
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