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Viral and Host Targets to Fight RNA Viruses

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 5791

Special Issue Editor


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Guest Editor
Department of Pharmaceutical Sciences, University of Perugia, 06125 Perugia, Italy
Interests: medicinal chemistry; organic chemistry; chemical biology; antibiotics; antiviral agents; anticancer agents; efflux pump inhibitors; polymerase inhibitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

RNA viruses include a wide range of human pathogens. The most studied and well known are the hepatotropic and lymphotropic hepatitis C virus, respiratory viruses such as influenza viruses and coronaviruses, as well as vector-borne viruses such as the flaviviruses Dengue, Zika, and West Nile, to mention only a few examples. Other RNA viruses, including Chikungunya, Rift Valley fever, Phlebovirus, and Nairovirus, are less studied, and less information on these is therefore available, but they can also represent a future challenge. Being present in reservoir hosts including rodents, bats, wild birds, or vectors such as ticks and mosquitoes, RNA viruses are often the cause of human epidemics and, occasionally, pandemics. Unfortunately, antiviral therapeutics to treat most viral diseases have not yet been discovered or, if available, are often subject to side effects and the onset of resistance. Accordingly, research focused on the discovery of new approaches to fight RNA viruses is in strong demand and is dependent on close cooperation between different scientific areas such as biochemistry, virology, medicinal and organic chemistries, and chemical, cellular, and molecular biology.

This Special Issue aims to collect studies focused on i) the discovery of novel antiviral agents (direct-acting and host-targeting agents), ii) the investigation of mechanisms of action, and iii) the identification of new druggable targets. High-quality reviews and original papers focused on novel approaches to fight RNA viruses are welcome. Theoretical studies are encouraged only if supported by experimental validation.

Dr. Tommaso Felicetti
Guest Editor

Manuscript Submission Information

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Keywords

  • RNA viruses
  • antiviral agents
  • medicinal chemistry
  • direct-acting antivirals
  • host-targeting agents
  • drug design

Published Papers (4 papers)

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Research

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19 pages, 2800 KiB  
Article
Nucleotide-Binding Oligomerization Domain 1 (NOD1) Agonists Prevent SARS-CoV-2 Infection in Human Lung Epithelial Cells through Harnessing the Innate Immune Response
by Edurne Garcia-Vidal, Ignasi Calba, Eva Riveira-Muñoz, Elisabet García, Bonaventura Clotet, Pere Serra-Mitjà, Cecilia Cabrera, Ester Ballana and Roger Badia
Int. J. Mol. Sci. 2024, 25(10), 5318; https://doi.org/10.3390/ijms25105318 - 13 May 2024
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Abstract
The lung is prone to infections from respiratory viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A challenge in combating these infections is the difficulty in targeting antiviral activity directly at the lung mucosal tract. Boosting the capability of the respiratory [...] Read more.
The lung is prone to infections from respiratory viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A challenge in combating these infections is the difficulty in targeting antiviral activity directly at the lung mucosal tract. Boosting the capability of the respiratory mucosa to trigger a potent immune response at the onset of infection could serve as a potential strategy for managing respiratory infections. This study focused on screening immunomodulators to enhance innate immune response in lung epithelial and immune cell models. Through testing various subfamilies and pathways of pattern recognition receptors (PRRs), the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family was found to selectively activate innate immunity in lung epithelial cells. Activation of NOD1 and dual NOD1/2 by the agonists TriDAP and M-TriDAP, respectively, increased the number of IL-8+ cells by engaging the NF-κB and interferon response pathways. Lung epithelial cells showed a stronger response to NOD1 and dual NOD1/2 agonists compared to control. Interestingly, a less-pronounced response to NOD1 agonists was noted in PBMCs, indicating a tissue-specific effect of NOD1 in lung epithelial cells without inducing widespread systemic activation. The specificity of the NOD agonist pathway was confirmed through gene silencing of NOD1 (siRNA) and selective NOD1 and dual NOD1/2 inhibitors in lung epithelial cells. Ultimately, activation induced by NOD1 and dual NOD1/2 agonists created an antiviral environment that hindered SARS-CoV-2 replication in vitro in lung epithelial cells. Full article
(This article belongs to the Special Issue Viral and Host Targets to Fight RNA Viruses)
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22 pages, 2262 KiB  
Article
Antiviral Efficacy of RNase H-Dependent Gapmer Antisense Oligonucleotides against Japanese Encephalitis Virus
by Shunsuke Okamoto, Yusuke Echigoya, Ayaka Tago, Takao Segawa, Yukita Sato and Takuya Itou
Int. J. Mol. Sci. 2023, 24(19), 14846; https://doi.org/10.3390/ijms241914846 - 2 Oct 2023
Viewed by 1592
Abstract
RNase H-dependent gapmer antisense oligonucleotides (ASOs) are a promising therapeutic approach via sequence-specific binding to and degrading target RNAs. However, the efficacy and mechanism of antiviral gapmer ASOs have remained unclear. Here, we investigated the inhibitory effects of gapmer ASOs containing locked nucleic [...] Read more.
RNase H-dependent gapmer antisense oligonucleotides (ASOs) are a promising therapeutic approach via sequence-specific binding to and degrading target RNAs. However, the efficacy and mechanism of antiviral gapmer ASOs have remained unclear. Here, we investigated the inhibitory effects of gapmer ASOs containing locked nucleic acids (LNA gapmers) on proliferating a mosquito-borne flavivirus, Japanese encephalitis virus (JEV), with high mortality. We designed several LNA gapmers targeting the 3′ untranslated region of JEV genomic RNAs. In vitro screening by plaque assay using Vero cells revealed that LNA gapmers targeting a stem-loop region effectively inhibit JEV proliferation. Cell-based and RNA cleavage assays using mismatched LNA gapmers exhibited an underlying mechanism where the inhibition of viral production results from JEV RNA degradation by LNA gapmers in a sequence- and modification-dependent manner. Encouragingly, LNA gapmers potently inhibited the proliferation of five JEV strains of predominant genotypes I and III in human neuroblastoma cells without apparent cytotoxicity. Database searching showed a low possibility of off-target binding of our LNA gapmers to human RNAs. The target viral RNA sequence conservation observed here highlighted their broad-spectrum antiviral potential against different JEV genotypes/strains. This work will facilitate the development of an antiviral LNA gapmer therapy for JEV and other flavivirus infections. Full article
(This article belongs to the Special Issue Viral and Host Targets to Fight RNA Viruses)
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17 pages, 3688 KiB  
Article
Novel Antiviral Molecules against Ebola Virus Infection
by Mila Collados Rodríguez, Patrick Maillard, Alexandra Journeaux, Anastassia V. Komarova, Valérie Najburg, Raul-Yusef Sanchez David, Olivier Helynck, Mingzhe Guo, Jin Zhong, Sylvain Baize, Frédéric Tangy, Yves Jacob, Hélène Munier-Lehmann and Eliane F. Meurs
Int. J. Mol. Sci. 2023, 24(19), 14791; https://doi.org/10.3390/ijms241914791 - 30 Sep 2023
Viewed by 1396
Abstract
Infection with Ebola virus (EBOV) is responsible for hemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the [...] Read more.
Infection with Ebola virus (EBOV) is responsible for hemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I3D chemical library using a nanoluciferase-based protein complementation assay (NPCA) and isolated two compounds that disrupt the interaction of the EBOV protein fragment VP35IID with the N-terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose that the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, our data support further testing of the compounds in other species, as well as against other negative-sense RNA viruses. Full article
(This article belongs to the Special Issue Viral and Host Targets to Fight RNA Viruses)
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Review

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28 pages, 838 KiB  
Review
The Diagnostic, Prognostic, and Therapeutic Potential of Cell-Free DNA with a Special Focus on COVID-19 and Other Viral Infections
by Galina Hovhannisyan, Tigran Harutyunyan, Rouben Aroutiounian and Thomas Liehr
Int. J. Mol. Sci. 2023, 24(18), 14163; https://doi.org/10.3390/ijms241814163 - 15 Sep 2023
Viewed by 1982
Abstract
Cell-free DNA (cfDNA) in human blood serum, urine, and other body fluids recently became a commonly used diagnostic marker associated with various pathologies. This is because cfDNA enables a much higher sensitivity than standard biochemical parameters. The presence of and/or increased level of [...] Read more.
Cell-free DNA (cfDNA) in human blood serum, urine, and other body fluids recently became a commonly used diagnostic marker associated with various pathologies. This is because cfDNA enables a much higher sensitivity than standard biochemical parameters. The presence of and/or increased level of cfDNA has been reported for various diseases, including viral infections, including COVID-19. Here, we review cfDNA in general, how it has been identified, where it can derive from, its molecular features, and mechanisms of release and clearance. General suitability of cfDNA for diagnostic questions, possible shortcomings and future directions are discussed, with a special focus on coronavirus infection. Full article
(This article belongs to the Special Issue Viral and Host Targets to Fight RNA Viruses)
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