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Pathogens
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Virus–Host Cell Interactions and Research of New Antivirals
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Virus–Host Cell Interactions and Research of New Antivirals

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (31 August 2025) | Viewed by 6381

Special Issue Editors

Dr. Ligia Carla Faccin-Galhardi

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Guest Editor
Laboratório de Virologia Básica e Aplicada, Departamento de Microbiologia, Universidade Estadual de Londrina, Londrina 86057-970, Paraná, Brazil
Interests: viral replication; mechanism of action; research and innovation
Dr. Sueli F. Yamada-Ogatta

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Guest Editor
Laboratory of Molecular Biology of Microorganisms, Department of Microbiology, State University of Londrina, Londrina, Brazil
Interests: antimicrobial activity; antibiofilm activity; virulence; natural products
Special Issues, Collections and Topics in MDPI journals
Dr. Cybele Carina García

E-Mail Website
Guest Editor
Laboratório de Virologia, Departamento de Química Biológica, Universidad de Buenos Aires, Buenos Aires, Argentina
Interests: medicinal chemistry; natural products; antivirals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Viral infections pose a constant threat to global health security, whether due to their wide distribution, ease of transmission, and difficult control strategies, associated with the resistance demonstrated by certain viral strains. The restricted number of viruses and, consequently, of viral diseases controlled/treatable by antivirals is notorious. The difficulty in research and development of new antiviral molecules comes up against the specific characteristics of viruses with an extremely simple structure and intracellular replication, making selectivity in infected cells difficult, in addition to dependence on the host's response. In addition to these factors, there are laboratory limitations for handling viruses in in vitro and in vivo models. Understanding the mechanisms of virus–host cell interaction and strategies to control viral infections, aiming at the development of new molecules and/or antivirals, is extremely important. Thus, review manuscripts and research articles encompassing the proposed topics are very welcome in this Special Issue.

Dr. Ligia Carla Faccin-Galhardi
Dr. Sueli F. Yamada-Ogatta
Dr. Cybele Carina García
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. Pathogens 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 2200 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

  • virus infection
  • stages of viral replication
  • virulence
  • virus–host relationship
  • medicinal chemistry
  • natural products
  • antivirals
  • mechanism of action
  • research and innovation

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Published Papers (6 papers)

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Research

27 pages, 3758 KB  
Article
Exploring the Virome of Nile Tilapia (Oreochromis niloticus) Using Metagenomic Analysis
by Amira Ezzat, Ahmed Abd El Wahed, Arianna Ceruti, Amel M. El Asely, Mohamed Shawky Khalifa, Andrew D. Winters, Uwe Truyen, Adel A. Shaheen and Mohamed Faisal
Pathogens 2025, 14(9), 935; https://doi.org/10.3390/pathogens14090935 - 16 Sep 2025
Viewed by 138
Abstract
Nile tilapia (Oreochromis niloticus) is an indispensable source of high-quality protein worldwide. Along with the exponential expansion of tilapia aquaculture, several novel pathogenic viruses have emerged, and some cause significant economic losses. Unfortunately, there is scarce information on the biology and [...] Read more.
Nile tilapia (Oreochromis niloticus) is an indispensable source of high-quality protein worldwide. Along with the exponential expansion of tilapia aquaculture, several novel pathogenic viruses have emerged, and some cause significant economic losses. Unfortunately, there is scarce information on the biology and epidemiology of these viruses. This exploratory metagenomic study used Oxford Nanopore Technology (ONT) sequencing to profile the virome compositions of both wild and farmed Nile tilapia across five regions in Egypt. The Nile tilapia virome was dominated by two double-stranded DNA bacteriophages, Muvirus mu and M. sfmu, which constituted 79.8% of the detected sequences. Eukaryotic viruses, including members of the families Amnoonviridae, Peribunyaviridae, and Baculoviridae, were also identified. Two giant DNA viruses known to infect Acanthamoeba spp., Mollivirus sp., and Pandoravirus sp. were identified in the spleen virome of tilapia from a single sampling site. The diversity analysis showed no significant differences among tissue types or sampling sites. Phylogenetic analyses were performed on a single virus detected of potential pathogenicity, an amnoonvirus. The analyses demonstrated that the detected virus is a member of the family Amnoonviridae and placed it alongside members of the Tilapinevirus genus. The virus, however, was distinct from the other two members in the genus: T. tilapae and T. poikilos. This study underscores the usefulness of ONT in providing a foundational understanding of the Nile tilapia virome. Full article
(This article belongs to the Special Issue Virus–Host Cell Interactions and Research of New Antivirals)
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20 pages, 683 KB  
Article
Polymorphism of BoLA-DRB3 in Semen and Its Influence on Progeny Derived from Semen with Resistance and Susceptibility to Bovine Leukemia Virus Proviral Load
by Aronggaowa Bao, Sonoko Watanuki, Ryosuke Matsuura, Yasunobu Matsumoto, Jinliang Wang, Hiroyuki Shimizu, Ayuha Niwano, Ryusaku Kawata and Yoko Aida
Pathogens 2025, 14(9), 837; https://doi.org/10.3390/pathogens14090837 - 22 Aug 2025
Viewed by 547
Abstract
Bovine leukemia virus (BLV) is widespread globally and causes economic losses in the cattle industry. BoLA-DRB3 is a polymorphic gene associated with the BLV proviral load (PVL), which correlates with disease progression and transmission risk. However, the distribution of BoLA-DRB3 alleles in semen [...] Read more.
Bovine leukemia virus (BLV) is widespread globally and causes economic losses in the cattle industry. BoLA-DRB3 is a polymorphic gene associated with the BLV proviral load (PVL), which correlates with disease progression and transmission risk. However, the distribution of BoLA-DRB3 alleles in semen and their potential impact on the PVL of progeny remain unclear. Here, we investigated whether BLV susceptibility linked to BoLA-DRB3 alleles in semen is inherited by progeny. We analyzed 178 commercial semen samples from Japanese Black sires and identified 20 BoLA-DRB3 alleles and 70 genotypes. The susceptible allele DRB3*016:01 was the most frequent (26.4%), whereas resistant alleles DRB3*011:01 (5.3%) and DRB3*009:02 (0.6%) were rare. Subsequently, we collected blood samples from 200 progeny produced by artificial insemination using 36 of the 178 semen samples. Progeny derived from semen carrying at least one susceptible allele and no resistant alleles had significantly higher PVL in the blood than those derived from semen containing at least one resistant allele. These findings demonstrate that BLV susceptibility is inherited via BoLA-DRB3 alleles in semen and highlight the potential of BoLA-DRB3 alleles as valuable markers in breeding strategies aimed at mitigating BLV infection and transmission. Full article
(This article belongs to the Special Issue Virus–Host Cell Interactions and Research of New Antivirals)
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21 pages, 4238 KB  
Article
Relationship Between Cell Surface Viral Glycoprotein Expression and Resistance of Parainfluenza Virus Persistently Infected Cells to Complement-Mediated Lysis
by Nasser N. Yousef and Griffith D. Parks
Pathogens 2025, 14(8), 815; https://doi.org/10.3390/pathogens14080815 - 17 Aug 2025
Viewed by 530
Abstract
Persistent RNA virus infections (PI) are often characterized by extended viral shedding and maintained cycles of inflammation. The innate immune Complement (C′) pathways can recognize acute infected (AI) cells and result in their lysis, but the relative sensitivity of PI cells to C′-directed [...] Read more.
Persistent RNA virus infections (PI) are often characterized by extended viral shedding and maintained cycles of inflammation. The innate immune Complement (C′) pathways can recognize acute infected (AI) cells and result in their lysis, but the relative sensitivity of PI cells to C′-directed killing is incompletely understood. Here, we extended our previous studies on the interactions of C′ with parainfluenza virus AI and PI A549 cells to two additional respiratory tract cell lines. AI Hep2 and H1975 cells infected with Parainfluenza virus 5 (PIV5) were found to be highly sensitive to C′ lysis. By contrast, PIV5 PI cells were highly resistant to killing by C″. Surface deposition of membrane attack complex (MAC) and C3 was also greatly reduced on the surface of PI cells compared to AI cells. PI cells had lower levels of surface viral glycoprotein expression compared to AI cells. Treatment of AI cells with ribavirin (RBV) showed a dose-dependent decrease in both viral glycoprotein expression and sensitivity to C′-mediated lysis. When surface viral glycoprotein levels were reduced in AI cells to those in PI cells, AI cells became similarly resistant to C′. While sialic acid levels on PI cell surfaces matched that of naïve cells, enzymatic removal of this sialic acid did not increase sensitivity to C′-mediated lysis. Despite their varying profiles of C′ activation and deposition, these studies indicate downregulation of viral gene expression as a common mechanism of C′ resistance across various parainfluenza virus PI cell lines. Full article
(This article belongs to the Special Issue Virus–Host Cell Interactions and Research of New Antivirals)
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13 pages, 1921 KB  
Article
Antiviral Activity of Haematococcus pluvialis Algae Extract Is Not Exclusively Due to Astaxanthin
by Paula Peinsipp, Tanja Gerlza, Julia Kircher, Kurt Zatloukal, Corinna Jäger, Peter Pucher and Andreas J. Kungl
Pathogens 2025, 14(8), 791; https://doi.org/10.3390/pathogens14080791 - 7 Aug 2025
Viewed by 664
Abstract
In this study, astaxanthin, which has previously been shown to have antiviral effects, was examined for its dose-dependent potency to inhibit cellular SARS-CoV-2 infections. Naturally occurring astaxanthin is obtained and orally administered as ASX-oleoresin, a composition of different astaxanthin fatty acid esters. We [...] Read more.
In this study, astaxanthin, which has previously been shown to have antiviral effects, was examined for its dose-dependent potency to inhibit cellular SARS-CoV-2 infections. Naturally occurring astaxanthin is obtained and orally administered as ASX-oleoresin, a composition of different astaxanthin fatty acid esters. We therefore hypothesized that the compound’s beneficial effects are not only related to astaxanthin. Thus, a “green” algae extract (i.e., poor astaxanthin content < 0.2%; ASXp) of the microalgae Haematococcus pluvialis, as well as an astaxanthin-rich algae extract (astaxanthin content = 20%; ASXr), were tested in in vitro cellular viral infection assays. Thereby, it was found that both extracts reduced viral infections significantly. As a potential mode of inhibitory action, the binding of ASX-oleoresin to the viral spike protein was investigated by isothermal fluorescence titration, revealing binding affinities of Kd = 1.05 µM for ASXr and Kd = 1.42 µM for ASXp. Based on our data, we conclude that several ASX-oleoresin fractions from H. pluvialis exhibit antiviral activity, which extends beyond the known antioxidant activity of astaxanthin. From a molecular dynamic simulation of ASX-oleoresin, fatty acid domains could be considered as activity-chaperoning factors of ASX. Therefore, microalgae biomass should be considered in the future for further antiviral activities. Full article
(This article belongs to the Special Issue Virus–Host Cell Interactions and Research of New Antivirals)
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16 pages, 1234 KB  
Article
Antiviral Effect of Erdosteine in Cells Infected with Human Respiratory Viruses
by Pierachille Santus, Sergio Strizzi, Fiammetta Danzo, Mara Biasin, Irma Saulle, Claudia Vanetti, Marina Saad, Dejan Radovanovic and Daria Trabattoni
Pathogens 2025, 14(4), 388; https://doi.org/10.3390/pathogens14040388 - 15 Apr 2025
Viewed by 1310
Abstract
Respiratory viral infections trigger immune and inflammatory responses that can be associated with excessive oxidative stress, glutathione (GSH) depletion, and a cytokine storm that drives virus-induced cell/tissue damage and severe disease. Erdosteine is a thiol-based drug with proven mucolytic, anti-inflammatory, antioxidant, and antibacterial [...] Read more.
Respiratory viral infections trigger immune and inflammatory responses that can be associated with excessive oxidative stress, glutathione (GSH) depletion, and a cytokine storm that drives virus-induced cell/tissue damage and severe disease. Erdosteine is a thiol-based drug with proven mucolytic, anti-inflammatory, antioxidant, and antibacterial properties, but less is known about its antiviral effects. We performed in vitro studies to investigate the antiviral and anti-inflammatory activity of erdosteine in A549-hACE2 human lung epithelial cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or respiratory syncytial virus (RSV) and in Caco-2 human colon carcinoma cells infected with influenza A virus (H1N1). The cells were treated with different concentrations of erdosteine or its active metabolite 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MET-1) before and after viral infection. The viral replication/load in the cell culture supernatants was measured by real-time quantitative polymerase chain reaction (RT-qPCR) assay and digital droplet PCR. The gene expression of innate immune response signaling pathways and oxidative stress was analyzed by reverse transcription PCR custom-array. The results showed that erdosteine and its active metabolite, at concentrations consistent with an approved therapeutic human dosage, were not directly cytotoxic and had significant antiviral effects in cells pre-infected with SARS-CoV-2, RSV, and H1N1. The transcriptome analysis showed that erdosteine activated innate immune responses by stimulating overexpression of type I interferon and inflammasome pathways and modulated oxidative stress by inducing the modulation of oxidative stress and GSH pathways. These findings suggest that erdosteine may be a useful treatment for respiratory viral infections. Full article
(This article belongs to the Special Issue Virus–Host Cell Interactions and Research of New Antivirals)
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15 pages, 3034 KB  
Article
CRISPR/Cas9 Eye Drop HSV-1 Treatment Reduces Brain Viral Load: A Novel Application to Prevent Neuronal Damage
by Rafaela Moraes Pereira de Sousa, Luiza Silveira Garcia, Felipe Simões Lemos, Viviane Souza de Campos, Erik Machado Ferreira, Nathália Alves Araujo de Almeida, Tatiana Maron-Gutierrez, Elen Mello de Souza and Vanessa Salete de Paula
Pathogens 2024, 13(12), 1087; https://doi.org/10.3390/pathogens13121087 - 10 Dec 2024
Cited by 2 | Viewed by 2437
Abstract
Herpes simplex virus-1 (HSV-1) can invade the central nervous system (CNS). However, antiviral drugs used to treat HSV-1 have significant toxicity and resistance. An alternative approach involves the use of the CRISPR/Cas9 complex as a viral replication inhibitor. Editing the UL39 gene with [...] Read more.
Herpes simplex virus-1 (HSV-1) can invade the central nervous system (CNS). However, antiviral drugs used to treat HSV-1 have significant toxicity and resistance. An alternative approach involves the use of the CRISPR/Cas9 complex as a viral replication inhibitor. Editing the UL39 gene with CRISPR/Cas9 results in >95% inhibition of HSV-1 replication in vitro; however, few studies have investigated alternative therapies in in vivo models. This study aimed to investigate the efficacy of CRISPR/Cas9 targeting the UL39 region, which was administered via the ocular route, to reduce the HSV-1 viral count in the CNS of BALB/c mice. Mice were inoculated with HSV-1 and treated using CRISPR/Cas9. The kinetics of CNS infection were assessed, and the effects of CRISPR/Cas9 were compared with those of topical acyclovir treatments. The brain viral load was analyzed, and histopathology and immunofluorescence of the nervous tissue were performed. The group treated with CRISPR/Cas9 showed a reduced viral load on the seventh day post-infection, and no brain inflammation or chromatin compaction was observed in animals that received CRISPR/Cas9 therapy. These findings suggest that CRISPR/Cas9 anti-UL39 therapy can reduce the HSV-1 viral load in brain tissue. Therefore, investigating viral detection and evaluating antiviral treatments in the brain is essential. Full article
(This article belongs to the Special Issue Virus–Host Cell Interactions and Research of New Antivirals)
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