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Pharmaceuticals
Special Issues
HIV and Viral Hepatitis: Prevention, Treatment and Coinfection
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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: closed (24 June 2024) | Viewed by 3099

Special Issue Editors

Dr. Daniel Sepúlveda-Crespo

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: hepatitis C virus; HIV; infectious diseases; virology; nanomedicine; neutralizing antibody
Dr. Salvador Resino

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
Special Issues, Collections and Topics in MDPI journals

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

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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 (3 papers)

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Research

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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 1532
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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Review

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33 pages, 1718 KiB  
Review
Insights into Immune Exhaustion in Chronic Hepatitis B: A Review of Checkpoint Receptor Expression
by João Panão Costa, Armando de Carvalho, Artur Paiva and Olga Borges
Pharmaceuticals 2024, 17(7), 964; https://doi.org/10.3390/ph17070964 (registering DOI) - 21 Jul 2024
Abstract
Hepatitis B, caused by the hepatitis B virus (HBV), often progresses to chronic infection, leading to severe complications, such as cirrhosis, liver failure, and hepatocellular carcinoma. Chronic HBV infection is characterized by a complex interplay between the virus and the host immune system, [...] Read more.
Hepatitis B, caused by the hepatitis B virus (HBV), often progresses to chronic infection, leading to severe complications, such as cirrhosis, liver failure, and hepatocellular carcinoma. Chronic HBV infection is characterized by a complex interplay between the virus and the host immune system, resulting in immune cell exhaustion, a phenomenon commonly observed in chronic viral infections and cancer. This state of exhaustion involves elevated levels of inhibitory molecules, cells, and cell surface receptors, as opposed to stimulatory counterparts. This review aims to elucidate the expression patterns of various co-inhibitory and co-stimulatory receptors on immune cells isolated from chronic hepatitis B (CHB) patients. By analyzing existing data, the review conducts comparisons between CHB patients and healthy adults, explores the differences between HBV-specific and total T cells in CHB patients, and examines variations between intrahepatic and peripheral immune cells in CHB patients. Understanding the mechanisms underlying immune exhaustion in CHB is crucial for developing novel immunotherapeutic approaches. This detailed analysis sheds light on the immune exhaustion observed in CHB and lays the groundwork for future combined immunotherapy strategies aimed at leveraging checkpoint receptors to restore immune function and improve clinical outcomes. Full article
(This article belongs to the Special Issue HIV and Viral Hepatitis: Prevention, Treatment and Coinfection)
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13 pages, 1024 KiB  
Review
Development of Anti-HIV Therapeutics: From Conventional Drug Discovery to Cutting-Edge Technology
by Yaping Sun and Lingyun Wang
Pharmaceuticals 2024, 17(7), 887; https://doi.org/10.3390/ph17070887 - 4 Jul 2024
Viewed by 527
Abstract
The efforts to discover HIV therapeutics have continued since the first human immunodeficiency virus (HIV) infected patient was confirmed in the 1980s. Ten years later, the first HIV drug, zidovudine (AZT), targeting HIV reverse transcriptase, was developed. Meanwhile, scientists were enlightened to discover [...] Read more.
The efforts to discover HIV therapeutics have continued since the first human immunodeficiency virus (HIV) infected patient was confirmed in the 1980s. Ten years later, the first HIV drug, zidovudine (AZT), targeting HIV reverse transcriptase, was developed. Meanwhile, scientists were enlightened to discover new drugs that target different HIV genes, like integrase, protease, and host receptors. Combination antiretroviral therapy (cART) is the most feasible medical intervention to suppress the virus in people with HIV (PWH) and control the epidemic. ART treatment has made HIV a chronic infection rather than a fatal disease, but ART does not eliminate latent reservoirs of HIV-1 from the host cells; strict and life-long adherence to ART is required for the therapy to be effective in patients. In this review, we first discussed the scientific history of conventional HIV drug discovery since scientists need to develop more and more drugs to solve drug-resistant issues and release the side effects. Then, we summarized the novel research technologies, like gene editing, applied to HIV treatment and their contributions to eliminating HIV as a complementary therapy. Full article
(This article belongs to the Special Issue HIV and Viral Hepatitis: Prevention, Treatment and Coinfection)
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