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Molecular Research on Antiviral Mechanism

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

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 14384

Special Issue Editor


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Guest Editor
Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, New York, NY 14203, USA
Interests: infectious disease; molecular and cellular biology; transgenic organisms; viral pathogenesis; retroviruses; virology; virus pathogenesis; host-pathogens interactions; innate immunity; intrinsic immunity; coronaviruses; positive strand RNA viruses

Special Issue Information

Dear Colleagues,

Viruses are not able to survive on their own. Therefore, in order to propagate, they must infect cells, and as such, develop highly intricate mechanisms perform various cellular functions and defend themselves against the antiviral mechanisms implemented by infected cells. Viruses also take over signaling pathways and various processes within the host as a means of assisting their replication. Similarly, they have developed a diverse number of molecular strategies to block any cell-mediated antiviral responses. Viruses can modify, sequester and degrade the targets within a cell utilizing a multitude of mechanisms. These diverse strategies that viruses use to counteract the host cells at the molecular level have provided numerous potential targets for the development of antivirals.

In this Special Issue, we invite articles that highlight the latest developments and advancements in molecular research in virology. We are excited to invite papers on the molecular mechanisms that all viruses (both RNA and DNA viruses) utilize to take over the host cells, including those focused on the molecular strategies that host cells use to thwart the invading viral pathogens.

Dr. Spyridon Stavrou
Guest Editor

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Keywords

  • host pathogen interactions
  • RNA viruses
  • DNA viruses
  • cell intrinsic immunity
  • viral proteins
  • virus replication
  • restriction factors

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Published Papers (6 papers)

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Research

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9 pages, 1064 KiB  
Communication
Comparative Analysis of Viral Load Quantification Using Reverse Transcription Polymerase Chain Reaction and Digital Droplet Polymerase Chain Reaction
by Paula Gebe Abreu Cabral, Sávio Bastos de Souza, Raul Ferraz Arruda, Sheila Passos de Figueiredo Cabral, Arícia Leone Evangelista Monteiro de Assis, Yolanda Porto Muniz Martins, Antônio Brazil Viana Junior, Junbiao Chang, Pingsheng Lei and Renato Martins da Silva
Int. J. Mol. Sci. 2025, 26(2), 725; https://doi.org/10.3390/ijms26020725 - 16 Jan 2025
Viewed by 1242
Abstract
In the year 2019, a highly virulent coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, precipitating the outbreak of the illness known as coronavirus disease 2019 (COVID-19). The commonly employed reverse transcription polymerase chain reaction (RT-qPCR) methodology serves to estimate the [...] Read more.
In the year 2019, a highly virulent coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, precipitating the outbreak of the illness known as coronavirus disease 2019 (COVID-19). The commonly employed reverse transcription polymerase chain reaction (RT-qPCR) methodology serves to estimate the viral load in each patient’s sample by employing a standard curve. However, it is imperative to recognize that this technique exhibits limitations with respect to clinical diagnosis and therapeutic applications, since an advancement of the conventional polymerase chain reaction methods, digital polymerase chain reaction (digital PCR or DDPCR), enables the direct quantification and clonal amplification of nucleic acid strands. The primary divergence between dPCR and traditional PCR resides in their approaches to measuring nucleic acid quantities. In this study, we investigated the viral loads of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) within 461 participants. By employing both RT-qPCR and DDPCR techniques, we established a comparison between the quantification methodologies of the two approaches. Our findings illustrate that the quantification through DDPCR affords a superior means of monitoring viral load within lower respiratory tract samples, thus enhancing the assessment of disease progression, particularly in scenarios characterized by low viral loads. Full article
(This article belongs to the Special Issue Molecular Research on Antiviral Mechanism)
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19 pages, 4582 KiB  
Article
The Mechanism of Action of L-Tyrosine Derivatives against Chikungunya Virus Infection In Vitro Depends on Structural Changes
by Vanessa Loaiza-Cano, Estiven Hernández-Mira, Manuel Pastrana-Restrepo, Elkin Galeano, Daniel Pardo-Rodriguez and Marlen Martinez-Gutierrez
Int. J. Mol. Sci. 2024, 25(14), 7972; https://doi.org/10.3390/ijms25147972 - 21 Jul 2024
Cited by 1 | Viewed by 1585
Abstract
Although the disease caused by chikungunya virus (CHIKV) is of great interest to public health organizations around the world, there are still no authorized antivirals for its treatment. Previously, dihalogenated anti-CHIKV compounds derived from L-tyrosine (dH-Y) were identified as being effective against in [...] Read more.
Although the disease caused by chikungunya virus (CHIKV) is of great interest to public health organizations around the world, there are still no authorized antivirals for its treatment. Previously, dihalogenated anti-CHIKV compounds derived from L-tyrosine (dH-Y) were identified as being effective against in vitro infection by this virus, so the objective of this study was to determine the mechanisms of its antiviral action. Six dH-Y compounds (C1 to C6) dihalogenated with bromine or chlorine and modified in their amino groups were evaluated by different in vitro antiviral strategies and in silico tools. When the cells were exposed before infection, all compounds decreased the expression of viral proteins; only C4, C5 and C6 inhibited the genome; and C1, C2 and C3 inhibited infectious viral particles (IVPs). Furthermore, C1 and C3 reduce adhesion, while C2 and C3 reduce internalization, which could be related to the in silico interaction with the fusion peptide of the E1 viral protein. Only C3, C4, C5 and C6 inhibited IVPs when the cells were exposed after infection, and their effect occurred in late stages after viral translation and replication, such as assembly, and not during budding. In summary, the structural changes of these compounds determine their mechanism of action. Additionally, C3 was the only compound that inhibited CHIKV infection at different stages of the replicative cycle, making it a compound of interest for conversion as a potential drug. Full article
(This article belongs to the Special Issue Molecular Research on Antiviral Mechanism)
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23 pages, 5295 KiB  
Article
Proteomics Analysis of the Polyomavirus DNA Replication Initiation Complex Reveals Novel Functional Phosphorylated Residues and Associated Proteins
by Rama Dey-Rao, Shichen Shen, Jun Qu and Thomas Melendy
Int. J. Mol. Sci. 2024, 25(8), 4540; https://doi.org/10.3390/ijms25084540 - 21 Apr 2024
Cited by 2 | Viewed by 2347
Abstract
Polyomavirus (PyV) Large T-antigen (LT) is the major viral regulatory protein that targets numerous cellular pathways for cellular transformation and viral replication. LT directly recruits the cellular replication factors involved in initiation of viral DNA replication through mutual interactions between LT, DNA polymerase [...] Read more.
Polyomavirus (PyV) Large T-antigen (LT) is the major viral regulatory protein that targets numerous cellular pathways for cellular transformation and viral replication. LT directly recruits the cellular replication factors involved in initiation of viral DNA replication through mutual interactions between LT, DNA polymerase alpha-primase (Polprim), and single-stranded DNA binding complex, (RPA). Activities and interactions of these complexes are known to be modulated by post-translational modifications; however, high-sensitivity proteomic analyses of the PTMs and proteins associated have been lacking. High-resolution liquid chromatography tandem mass spectrometry (LC–MS/MS) of the immunoprecipitated factors (IPMS) identified 479 novel phosphorylated amino acid residues (PAARs) on the three factors; the function of one has been validated. IPMS revealed 374, 453, and 183 novel proteins associated with the three, respectively. A significant transcription-related process network identified by Gene Ontology (GO) enrichment analysis was unique to LT. Although unidentified by IPMS, the ETS protooncogene 1, transcription factor (ETS1) was significantly overconnected to our dataset indicating its involvement in PyV processes. This result was validated by demonstrating that ETS1 coimmunoprecipitates with LT. Identification of a novel PAAR that regulates PyV replication and LT’s association with the protooncogenic Ets1 transcription factor demonstrates the value of these results for studies in PyV biology. Full article
(This article belongs to the Special Issue Molecular Research on Antiviral Mechanism)
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27 pages, 17240 KiB  
Article
Unveiling the Role of Protein Kinase C θ in Porcine Epidemic Diarrhea Virus Replication: Insights from Genome-Wide CRISPR/Cas9 Library Screening
by Jinglin Zhou, Zhihua Feng, Deyang Lv, Duokai Wang, Kai Sang, Zhihao Liu, Dong Guo, Yangkun Shen and Qi Chen
Int. J. Mol. Sci. 2024, 25(6), 3096; https://doi.org/10.3390/ijms25063096 - 7 Mar 2024
Cited by 5 | Viewed by 2282
Abstract
Porcine epidemic diarrhea virus (PEDV), a member of the Alpha-coronavirus genus in the Coronaviridae family, induces acute diarrhea, vomiting, and dehydration in neonatal piglets. This study aimed to investigate the genetic dependencies of PEDV and identify potential therapeutic targets by using a single-guide [...] Read more.
Porcine epidemic diarrhea virus (PEDV), a member of the Alpha-coronavirus genus in the Coronaviridae family, induces acute diarrhea, vomiting, and dehydration in neonatal piglets. This study aimed to investigate the genetic dependencies of PEDV and identify potential therapeutic targets by using a single-guide RNA (sgRNA) lentiviral library to screen host factors required for PEDV infection. Protein kinase C θ (PKCθ), a calcium-independent member of the PKC family localized in the cell membrane, was found to be a crucial host factor in PEDV infection. The investigation of PEDV infection was limited in Vero and porcine epithelial cell-jejunum 2 (IPEC-J2) due to defective interferon production in Vero and the poor replication of PEDV in IPEC-J2. Therefore, identifying suitable cells for PEDV investigation is crucial. The findings of this study reveal that human embryonic kidney (HEK) 293T and L929 cells, but not Vero and IPEC-J2 cells, were suitable for investigating PEDV infection. PKCθ played a significant role in endocytosis and the replication of PEDV, and PEDV regulated the expression and phosphorylation of PKCθ. Apoptosis was found to be involved in PEDV replication, as the virus activated the PKCθ-B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) axis in HEK293T and L929 cells to increase viral endocytosis and replication via mitochondrial apoptosis. This study demonstrated the suitability of HEK293T and L929 cells for investigating PEDV infection and identified PKCθ as a host factor essential for PEDV infection. These findings provide valuable insights for the development of strategies and drug targets for PEDV infection. Full article
(This article belongs to the Special Issue Molecular Research on Antiviral Mechanism)
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19 pages, 2278 KiB  
Article
SARS-CoV-2 ORF7a Mutation Found in BF.5 and BF.7 Sublineages Impacts Its Functions
by Uddhav Timilsina, Emily B. Ivey, Sean Duffy, Arnon Plianchaisuk, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Jumpei Ito, Kei Sato and Spyridon Stavrou
Int. J. Mol. Sci. 2024, 25(4), 2351; https://doi.org/10.3390/ijms25042351 - 16 Feb 2024
Cited by 2 | Viewed by 2512
Abstract
A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of the ORF7a: H47Y mutation, in which the 47th residue of ORF7a has been mutated from a histidine (H) to a [...] Read more.
A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of the ORF7a: H47Y mutation, in which the 47th residue of ORF7a has been mutated from a histidine (H) to a tyrosine (Y). Here, we evaluated the effect of this mutation on the three main functions ascribed to the SARS-CoV-2 ORF7a protein. Our findings show that H47Y mutation impairs the ability of SARS-CoV-2 ORF7a to antagonize the type I interferon (IFN-I) response and to downregulate major histocompatibility complex I (MHC-I) cell surface levels, but had no effect in its anti-SERINC5 function. Overall, our results suggest that the H47Y mutation of ORF7a affects important functions of this protein, resulting in changes in virus pathogenesis. Full article
(This article belongs to the Special Issue Molecular Research on Antiviral Mechanism)
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Review

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21 pages, 1189 KiB  
Review
Immune Stimulation with Imiquimod to Best Face SARS-CoV-2 Infection and Prevent Long COVID
by Ursino Pacheco-García, Elvira Varela-López and Jeanet Serafín-López
Int. J. Mol. Sci. 2024, 25(14), 7661; https://doi.org/10.3390/ijms25147661 - 12 Jul 2024
Viewed by 3666
Abstract
Through widespread immunization against SARS-CoV-2 prior to or post-infection, a substantial segment of the global population has acquired both humoral and cellular immunity, and there has been a notable reduction in the incidence of severe and fatal cases linked to this virus [...] Read more.
Through widespread immunization against SARS-CoV-2 prior to or post-infection, a substantial segment of the global population has acquired both humoral and cellular immunity, and there has been a notable reduction in the incidence of severe and fatal cases linked to this virus and accelerated recovery times for those infected. Nonetheless, a significant demographic, comprising around 20% to 30% of the adult population, remains unimmunized due to diverse factors. Furthermore, alongside those recovered from the infection, there is a subset of the population experiencing persistent symptoms referred to as Long COVID. This condition is more prevalent among individuals with underlying health conditions and immune system impairments. Some Long COVID pathologies stem from direct damage inflicted by the viral infection, whereas others arise from inadequate immune system control over the infection or suboptimal immunoregulation. There are differences in the serum cytokines and miRNA profiles between infected individuals who develop severe COVID-19 or Long COVID and those who control adequately the infection. This review delves into the advantages and constraints associated with employing imiquimod in human subjects to enhance the immune response during SARS-CoV-2 immunization. Restoration of the immune system can modify it towards a profile of non-susceptibility to SARS-CoV-2. An adequate immune system has the potential to curb viral propagation, mitigate symptoms, and ameliorate the severe consequences of the infection. Full article
(This article belongs to the Special Issue Molecular Research on Antiviral Mechanism)
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