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Viruses
Special Issues
Host-Directed Therapies for HIV and RNA Respiratory Virus Infections
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Host-Directed Therapies for HIV and RNA Respiratory Virus Infections

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 14626

Special Issue Editors

Prof. Dr. Yuxian He

E-Mail Website
Guest Editor
Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Interests: HIV; SARS-CoV-2; antivirals; membrane fusion; fusion inhibitors; neutralizing antibodies; gene therapy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Nuno Taveira

E-Mail Website
Guest Editor
Research Institute for Medicines-FFUL (iMed.ULisboa), Universidade de Lisboa (University of Lisbon), Lisbon, Portugal
Interests: HIV; antivirals and vaccines; drug resistance; pathogenesis; antibody neutralization; virus evolution
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

HIV and RNA respiratory viruses such as influenza virus, respiratory syncytial virus (RSV) and SARS-CoV-2 cause high-burden diseases that disrupt healthcare systems and devastate economies. Except for HIV, few effective drugs are currently available for these viruses, and most are virus specific. An additional problem is the rapid development of drug resistance. The development of host-directed broad-spectrum antiviral agents that could overcome resistance is a high priority and would add resilience against pandemic threats caused by these viruses. This Special Issue of Viruses seeks to attract top-level publications on the design, development and validation of new host-directed antivirals to treat and prevent HIV and RNA respiratory virus infections. We invite you to share your most insightful primary research work, reviews and hypotheses on these important topics.

Prof. Dr. Yuxian He
Prof. Dr. Nuno Taveira
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. Viruses 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 2600 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

  • HIV infection
  • SARS-CoV-2 infection
  • Influenza infection
  • RSV infection
  • Host-directed therapies

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Published Papers (4 papers)

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Research

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18 pages, 8863 KiB  
Article
The Novel hDHODH Inhibitor MEDS433 Prevents Influenza Virus Replication by Blocking Pyrimidine Biosynthesis
by Giulia Sibille, Anna Luganini, Stefano Sainas, Donatella Boschi, Marco Lucio Lolli and Giorgio Gribaudo
Viruses 2022, 14(10), 2281; https://doi.org/10.3390/v14102281 - 17 Oct 2022
Cited by 6 | Viewed by 2399
Abstract
The pharmacological management of influenza virus (IV) infections still poses a series of challenges due to the limited anti-IV drug arsenal. Therefore, the development of new anti-influenza agents effective against antigenically different IVs is therefore an urgent priority. To meet this need, host-targeting [...] Read more.
The pharmacological management of influenza virus (IV) infections still poses a series of challenges due to the limited anti-IV drug arsenal. Therefore, the development of new anti-influenza agents effective against antigenically different IVs is therefore an urgent priority. To meet this need, host-targeting antivirals (HTAs) can be evaluated as an alternative or complementary approach to current direct-acting agents (DAAs) for the therapy of IV infections. As a contribution to this antiviral strategy, in this study, we characterized the anti-IV activity of MEDS433, a novel small molecule inhibitor of the human dihydroorotate dehydrogenase (hDHODH), a key cellular enzyme of the de novo pyrimidine biosynthesis pathway. MEDS433 exhibited a potent antiviral activity against IAV and IBV replication, which was reversed by the addition of exogenous uridine and cytidine or the hDHODH product orotate, thus indicating that MEDS433 targets notably hDHODH activity in IV-infected cells. When MEDS433 was used in combination either with dipyridamole (DPY), an inhibitor of the pyrimidine salvage pathway, or with an anti-IV DAA, such as N4-hydroxycytidine (NHC), synergistic anti-IV activities were observed. As a whole, these results indicate MEDS433 as a potential HTA candidate to develop novel anti-IV intervention approaches, either as a single agent or in combination regimens with DAAs. Full article
(This article belongs to the Special Issue Host-Directed Therapies for HIV and RNA Respiratory Virus Infections)
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10 pages, 826 KiB  
Article
Probenecid Inhibits Respiratory Syncytial Virus (RSV) Replication
by Jackelyn Murray, Harrison C. Bergeron, Les P. Jones, Zachary Beau Reener, David E. Martin, Fred D. Sancilio and Ralph A. Tripp
Viruses 2022, 14(5), 912; https://doi.org/10.3390/v14050912 - 27 Apr 2022
Cited by 13 | Viewed by 4110
Abstract
RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid, an FDA-approved and safe urate-lowering drug that inhibits organic anion transporters (OATs) has prophylactic or therapeutic efficacy to inhibit RSV replication [...] Read more.
RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid, an FDA-approved and safe urate-lowering drug that inhibits organic anion transporters (OATs) has prophylactic or therapeutic efficacy to inhibit RSV replication in three epithelial cell lines used in RSV studies, i.e., Vero E6 cells, HEp-2 cells, and in primary normal human bronchoepithelial (NHBE) cells, and in BALB/c mice. The studies showed that nanomolar concentrations of all probenecid regimens prevent RSV strain A and B replication in vitro and RSV strain A in vivo, representing a potential prophylactic and chemotherapeutic for RSV. Full article
(This article belongs to the Special Issue Host-Directed Therapies for HIV and RNA Respiratory Virus Infections)
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Review

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32 pages, 1627 KiB  
Review
Immunometabolic Signature during Respiratory Viral Infection: A Potential Target for Host-Directed Therapies
by Larissa Menezes dos Reis, Marcelo Rodrigues Berçot, Bianca Gazieri Castelucci, Ana Julia Estumano Martins, Gisele Castro and Pedro M. Moraes-Vieira
Viruses 2023, 15(2), 525; https://doi.org/10.3390/v15020525 - 13 Feb 2023
Cited by 5 | Viewed by 3383
Abstract
RNA viruses are known to induce a wide variety of respiratory tract illnesses, from simple colds to the latest coronavirus pandemic, causing effects on public health and the economy worldwide. Influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus [...] Read more.
RNA viruses are known to induce a wide variety of respiratory tract illnesses, from simple colds to the latest coronavirus pandemic, causing effects on public health and the economy worldwide. Influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus (RhV), and coronavirus (CoV) are some of the most notable RNA viruses. Despite efforts, due to the high mutation rate, there are still no effective and scalable treatments that accompany the rapid emergence of new diseases associated with respiratory RNA viruses. Host-directed therapies have been applied to combat RNA virus infections by interfering with host cell factors that enhance the ability of immune cells to respond against those pathogens. The reprogramming of immune cell metabolism has recently emerged as a central mechanism in orchestrated immunity against respiratory viruses. Therefore, understanding the metabolic signature of immune cells during virus infection may be a promising tool for developing host-directed therapies. In this review, we revisit recent findings on the immunometabolic modulation in response to infection and discuss how these metabolic pathways may be used as targets for new therapies to combat illnesses caused by respiratory RNA viruses. Full article
(This article belongs to the Special Issue Host-Directed Therapies for HIV and RNA Respiratory Virus Infections)
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21 pages, 1008 KiB  
Review
Single-Domain Antibodies as Therapeutics for Respiratory RNA Virus Infections
by Keke Huang, Tianlei Ying and Yanling Wu
Viruses 2022, 14(6), 1162; https://doi.org/10.3390/v14061162 - 27 May 2022
Cited by 6 | Viewed by 3698
Abstract
Over the years, infectious diseases with high morbidity and mortality disrupted human healthcare systems and devastated economies globally. Respiratory viruses, especially emerging or re-emerging RNA viruses, including influenza and human coronavirus, are the main pathogens of acute respiratory diseases that cause epidemics or [...] Read more.
Over the years, infectious diseases with high morbidity and mortality disrupted human healthcare systems and devastated economies globally. Respiratory viruses, especially emerging or re-emerging RNA viruses, including influenza and human coronavirus, are the main pathogens of acute respiratory diseases that cause epidemics or even global pandemics. Importantly, due to the rapid mutation of viruses, there are few effective drugs and vaccines for the treatment and prevention of these RNA virus infections. Of note, a class of antibodies derived from camelid and shark, named nanobody or single-domain antibody (sdAb), was characterized by smaller size, lower production costs, more accessible binding epitopes, and inhalable properties, which have advantages in the treatment of respiratory diseases compared to conventional antibodies. Currently, a number of sdAbs have been developed against various respiratory RNA viruses and demonstrated potent therapeutic efficacy in mouse models. Here, we review the current status of the development of antiviral sdAb and discuss their potential as therapeutics for respiratory RNA viral diseases. Full article
(This article belongs to the Special Issue Host-Directed Therapies for HIV and RNA Respiratory Virus Infections)
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