Pub Date : 2025-12-03DOI: 10.1016/j.virusres.2025.199672
Hui Cai , Lijing Hou , Jingjie Chang , Qing Yang , Mingming Wang , Lin Wang , Yao Li , Xueting Cai , Jie Yang , Peng Cao , Jiao Chen
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and the elderly, with limited treatment options. Venenum bufonis (Vb), a traditional Chinese medicine, exhibits broad pharmacological activities including antiviral and anti-inflammatory effects, but its potential against RSV-induced pneumonia remains unclear. This study evaluates Vb’s therapeutic effects and mechanisms in RSV-infected pneumonia and identifies its key active constituents. RSV pneumonia was induced in C57BL/6 mice via intranasal inoculation. Mice were treated with Vb or ribavirin intraperitoneally for five days. Lung pathology, viral gene, inflammatory cytokine gene expression, NLRP3 pathway activation, and immune cell infiltration were assessed using H&E staining, electron microscopy, RT-qPCR, immunohistochemistry, RNA sequencing and flow cytometry. The results demonstrated that Vb treatment significantly reduced lung tissue damage, mRNA levels of RSV-N protein, proinflammatory cytokines (TNF-α, IL-6) and type II interferon (IFN-γ), and enhanced the mRNA levels of type I interferons (IFN-α/β). Furthermore, Vb markedly decreased macrophage infiltration and suppressed mRNA expression of NLRP3, Caspase-1, and IL-1β in lung tissue, suggesting it may alleviate RSV pneumonia by inhibiting macrophage-driven inflammation and NLRP3 activation. Additionally, bufalin, cinobufagin, and resibufogenin were identified as likely bioactive constituents mediating Vb’s therapeutic effects. This study provides a scientific basis for the potential application of Vb in the treatment of RSV-induced pneumonia.
{"title":"Venenum bufonis and its active constituents alleviate RSV-induced pneumonia in mice by suppressing macrophage infiltration and NLRP3 inflammasome activation","authors":"Hui Cai , Lijing Hou , Jingjie Chang , Qing Yang , Mingming Wang , Lin Wang , Yao Li , Xueting Cai , Jie Yang , Peng Cao , Jiao Chen","doi":"10.1016/j.virusres.2025.199672","DOIUrl":"10.1016/j.virusres.2025.199672","url":null,"abstract":"<div><div>Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and the elderly, with limited treatment options. Venenum bufonis (Vb), a traditional Chinese medicine, exhibits broad pharmacological activities including antiviral and anti-inflammatory effects, but its potential against RSV-induced pneumonia remains unclear. This study evaluates Vb’s therapeutic effects and mechanisms in RSV-infected pneumonia and identifies its key active constituents. RSV pneumonia was induced in C57BL/6 mice via intranasal inoculation. Mice were treated with Vb or ribavirin intraperitoneally for five days. Lung pathology, viral gene, inflammatory cytokine gene expression, NLRP3 pathway activation, and immune cell infiltration were assessed using H&E staining, electron microscopy, RT-qPCR, immunohistochemistry, RNA sequencing and flow cytometry. The results demonstrated that Vb treatment significantly reduced lung tissue damage, mRNA levels of RSV-N protein, proinflammatory cytokines (TNF-α, IL-6) and type II interferon (IFN-γ), and enhanced the mRNA levels of type I interferons (IFN-α/β). Furthermore, Vb markedly decreased macrophage infiltration and suppressed mRNA expression of NLRP3, Caspase-1, and IL-1β in lung tissue, suggesting it may alleviate RSV pneumonia by inhibiting macrophage-driven inflammation and NLRP3 activation. Additionally, bufalin, cinobufagin, and resibufogenin were identified as likely bioactive constituents mediating Vb’s therapeutic effects. This study provides a scientific basis for the potential application of Vb in the treatment of RSV-induced pneumonia.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"363 ","pages":"Article 199672"},"PeriodicalIF":2.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.virusres.2025.199666
Wenhua Gao , Yanhong Yao , Yabo Sun , Wenjing Pu , Lin Xu
As popular companion animals, dogs present a potential risk for zoonotic viral transmission through close contact with humans. To characterize the fecal virome of dogs in Pingliang City, Gansu Province, China, we performed metatranscriptomic sequencing on 30 fecal samples pooled into three libraries, representing three distinct living environments. A total of 112,900,200 clean reads were obtained, revealing 16 viral genera spanning 15 families and highlighting a diverse viral community comprising animal viruses, bacteriophages, and plant viruses. Notably, we identified five known pathogenic viruses: canine astrovirus (3708 reads), canine dicipivirus (6578 reads), canine norovirus (16 reads), canine vesivirus (74 reads), and canine rotavirus (128 reads). Their presence suggests possible exposure events at the human-animal interface, although the infectivity and transmission risk require further experimental validation. These findings significantly expand our understanding of the canine virome and underscore the importance of “One Health” surveillance in companion animals. However, the actual zoonotic potential of the detected viruses, remains to be elucidated through further targeted investigation.
{"title":"Metatranscriptomic characterization of the canine fecal virome from pooled samples in Gansu, China","authors":"Wenhua Gao , Yanhong Yao , Yabo Sun , Wenjing Pu , Lin Xu","doi":"10.1016/j.virusres.2025.199666","DOIUrl":"10.1016/j.virusres.2025.199666","url":null,"abstract":"<div><div>As popular companion animals, dogs present a potential risk for zoonotic viral transmission through close contact with humans. To characterize the fecal virome of dogs in Pingliang City, Gansu Province, China, we performed metatranscriptomic sequencing on 30 fecal samples pooled into three libraries, representing three distinct living environments. A total of 112,900,200 clean reads were obtained, revealing 16 viral genera spanning 15 families and highlighting a diverse viral community comprising animal viruses, bacteriophages, and plant viruses. Notably, we identified five known pathogenic viruses: canine astrovirus (3708 reads), canine dicipivirus (6578 reads), canine norovirus (16 reads), canine vesivirus (74 reads), and canine rotavirus (128 reads). Their presence suggests possible exposure events at the human-animal interface, although the infectivity and transmission risk require further experimental validation. These findings significantly expand our understanding of the canine virome and underscore the importance of “One Health” surveillance in companion animals. However, the actual zoonotic potential of the detected viruses, remains to be elucidated through further targeted investigation.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199666"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.virusres.2025.199668
Xiaoxu Li, Minmin Xiao
Objective
Influenza A (H1N1) is a highly contagious and pathogenic respiratory disease. This retrospective study aims to provide a scientific basis for the early diagnosis of the malignant progression of the disease and the prediction of the prognosis of elderly patients with influenza A through a retrospective research analysis.
Methods
This study was a retrospective cohort study. A total of 97 elderly patients with influenza A (H1N1) admitted to the Second People’s Hospital of Wuhu City from November 2023 to February 2024 were included. By analyzing the patients' clinical data, laboratory test indicators (including routine serum biochemical and blood routine indicators), and pulmonary imaging examination results, the correlations between these indicators and disease progression, hospital stay duration, and pulmonary pathological changes were explored.
Result
The d-dimer level was significantly correlated with the hospital stay duration (P = 0.0413). The d-dimer level was significantly correlated with the pathological changes of pulmonary inflammation, fibrosis, calcification, and nodules (F = 2.623, P = 0.0437). Especially in patients with pulmonary inflammation, the d-dimer level was significantly elevated. A decrease in lymphocyte count was closely related to the occurrence of severe influenza A (P = 0.0355). The study also found that changes in the d-dimer level, together with increases in monocyte and white blood cell counts, indicated an increased risk of disease progression.
Conclusion
This study provides a new perspective for the clinical diagnosis and prognosis assessment of elderly patients with influenza A (H1N1) through a comprehensive analysis of indicators such as d-dimer, lymphocytes, monocytes, and white blood cell counts.
{"title":"Retrospective study on the correlation between biochemical and blood routine indexes and prognosis in elderly patients with influenza A (H1N1)","authors":"Xiaoxu Li, Minmin Xiao","doi":"10.1016/j.virusres.2025.199668","DOIUrl":"10.1016/j.virusres.2025.199668","url":null,"abstract":"<div><h3>Objective</h3><div>Influenza A (H1N1) is a highly contagious and pathogenic respiratory disease. This retrospective study aims to provide a scientific basis for the early diagnosis of the malignant progression of the disease and the prediction of the prognosis of elderly patients with influenza A through a retrospective research analysis.</div></div><div><h3>Methods</h3><div>This study was a retrospective cohort study. A total of 97 elderly patients with influenza A (H1N1) admitted to the Second People’s Hospital of Wuhu City from November 2023 to February 2024 were included. By analyzing the patients' clinical data, laboratory test indicators (including routine serum biochemical and blood routine indicators), and pulmonary imaging examination results, the correlations between these indicators and disease progression, hospital stay duration, and pulmonary pathological changes were explored.</div></div><div><h3>Result</h3><div>The <span>d</span>-dimer level was significantly correlated with the hospital stay duration (<em>P</em> = 0.0413). The <span>d</span>-dimer level was significantly correlated with the pathological changes of pulmonary inflammation, fibrosis, calcification, and nodules (<em>F</em> = 2.623, <em>P</em> = 0.0437). Especially in patients with pulmonary inflammation, the <span>d</span>-dimer level was significantly elevated. A decrease in lymphocyte count was closely related to the occurrence of severe influenza A (<em>P</em> = 0.0355). The study also found that changes in the <span>d</span>-dimer level, together with increases in monocyte and white blood cell counts, indicated an increased risk of disease progression.</div></div><div><h3>Conclusion</h3><div>This study provides a new perspective for the clinical diagnosis and prognosis assessment of elderly patients with influenza A (H1N1) through a comprehensive analysis of indicators such as <span>d</span>-dimer, lymphocytes, monocytes, and white blood cell counts.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199668"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.virusres.2025.199670
Uri Gabbay , Doron Carmi
Seasonal influenza A virus (SIAV) apparently exhibits a paradoxical pattern: despite a lower basic reproduction number (R₀) than SARS-CoV-2, it propagates across the Northern Hemisphere with remarkable speed and synchronicity. We propose a testable hypothesis, developed in two conceptual steps to explain this phenomenon.
First, we discuss what may explain the rapid, near-synchronous propagation of SIAV seasonal outbreak. We suggest that it may result from parallel seeding from multiple sources, rather than emerging from a singular origin, as observed with COVID-19. Second, we examined potential mechanisms for parallel seeding.
We propose a hypothesis-generating framework that, despite its limitations, offers a structured approach for integrating avian ecology with human epidemiology. The hypothesis is testable through genomic and metagenomic methods. Sequencing viruses from humans and migratory birds across regions may be evaluated to reveal identical viral lineages. The hypothesis may highlight the potential role of ecological reservoirs in global influenza propagation dynamics. If validated, this framework would advance understanding of influenza seasonality and may guide integrated surveillance strategies linking avian ecology with human epidemiology.
{"title":"The paradox of rapid and synchronized propagation of seasonal influenza ‘A’ outbreaks in contrast with COVID-19: a testable hypothesis","authors":"Uri Gabbay , Doron Carmi","doi":"10.1016/j.virusres.2025.199670","DOIUrl":"10.1016/j.virusres.2025.199670","url":null,"abstract":"<div><div>Seasonal influenza A virus (SIAV) apparently exhibits a paradoxical pattern: despite a lower basic reproduction number (R₀) than SARS-CoV-2, it propagates across the Northern Hemisphere with remarkable speed and synchronicity. We propose a testable hypothesis, developed in two conceptual steps to explain this phenomenon.</div><div>First, we discuss what may explain the rapid, near-synchronous propagation of SIAV seasonal outbreak. We suggest that it may result from parallel seeding from multiple sources, rather than emerging from a singular origin, as observed with COVID-19. Second, we examined potential mechanisms for parallel seeding.</div><div>We propose a hypothesis-generating framework that, despite its limitations, offers a structured approach for integrating avian ecology with human epidemiology. The hypothesis is testable through genomic and metagenomic methods. Sequencing viruses from humans and migratory birds across regions may be evaluated to reveal identical viral lineages. The hypothesis may highlight the potential role of ecological reservoirs in global influenza propagation dynamics. If validated, this framework would advance understanding of influenza seasonality and may guide integrated surveillance strategies linking avian ecology with human epidemiology.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199670"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145640133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.virusres.2025.199669
Yansong Chen , Xinyu Zhang , Asha Ashuo , Zhong Fang , Wuhui Song , Jiangxia Liu , Jieliang Chen , Yaming Li , Zhenghong Yuan
The detection of hepatitis B surface antigen (HBsAg) is fundamental for the diagnosis of chronic hepatitis B (CHB). However, current diagnostic assays that rely on antibodies targeting the conformational “a” determinant of HBsAg are frequently compromised by mutations in this region, leading to undetected immune escape variants. In this study, we generated a novel monoclonal antibody, designated S1705, by immunizing mice with CHO-derived HBsAg. This antibody was identified to recognize a conserved linear epitope located within the internal loop region of the HBsAg particle. Western blot analysis under denaturing conditions confirmed that S1705 robustly detects HBsAg from multiple genotypes (A-D) and common clinical mutants, including the prevalent G145R variant. Moreover, S1705 demonstrated effective utility in applications such as flow cytometry and immunofluorescence. Notably, it exhibited superior performance compared to commercial antibodies targeting conformational epitopes in detecting HBsAg escape variants. We conclude that S1705, by targeting a conserved linear epitope, enables broad and reliable detection of both wild-type and mutant HBsAg. Critically, our findings demonstrate that immunodominant antigenic regions exist beyond the conventional boundaries of the ‘a’ determinant. This antibody thus holds significant promise for enhancing the diagnostic coverage of HBV variants and supporting future antiviral research and clinical monitoring.
{"title":"A novel monoclonal antibody targeting a conserved inner region of the hepatitis B virus envelope enables broad detection of immune escape variants","authors":"Yansong Chen , Xinyu Zhang , Asha Ashuo , Zhong Fang , Wuhui Song , Jiangxia Liu , Jieliang Chen , Yaming Li , Zhenghong Yuan","doi":"10.1016/j.virusres.2025.199669","DOIUrl":"10.1016/j.virusres.2025.199669","url":null,"abstract":"<div><div>The detection of hepatitis B surface antigen (HBsAg) is fundamental for the diagnosis of chronic hepatitis B (CHB). However, current diagnostic assays that rely on antibodies targeting the conformational “a” determinant of HBsAg are frequently compromised by mutations in this region, leading to undetected immune escape variants. In this study, we generated a novel monoclonal antibody, designated S1705, by immunizing mice with CHO-derived HBsAg. This antibody was identified to recognize a conserved linear epitope located within the internal loop region of the HBsAg particle. Western blot analysis under denaturing conditions confirmed that S1705 robustly detects HBsAg from multiple genotypes (A-D) and common clinical mutants, including the prevalent G145R variant. Moreover, S1705 demonstrated effective utility in applications such as flow cytometry and immunofluorescence. Notably, it exhibited superior performance compared to commercial antibodies targeting conformational epitopes in detecting HBsAg escape variants. We conclude that S1705, by targeting a conserved linear epitope, enables broad and reliable detection of both wild-type and mutant HBsAg. Critically, our findings demonstrate that immunodominant antigenic regions exist beyond the conventional boundaries of the ‘a’ determinant. This antibody thus holds significant promise for enhancing the diagnostic coverage of HBV variants and supporting future antiviral research and clinical monitoring.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199669"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.virusres.2025.199671
Kangli Li , Boning Zhu , Shuo Wang , Xiangle Zhang , Xiaodan Wen , Weijun Cao , Guoliang Zhu , Haixue Zheng , Fan Yang , Zixiang Zhu
Foot-and-mouth disease virus (FMDV) is the etiological agent of foot-and-mouth disease (FMD), which is highly contagious and extremely destructive in cloven-hoofed animals. Previous studies have shown that FMDV strongly suppress the innate immune response, and the research mainly focused on FMDV 3C and L proteinase. However, the role of FMDV 3D polymerase, an RNA-dependent RNA polymerase (RdRp), in inhibiting the IFN signaling pathway remains unclear. In this study, for the first time, we demonstrate that the highly conserved 3D polymerase of FMDV inhibits the activation of the JAK-STAT signaling pathway by targeting STAT2. Mechanistically, FMDV 3D significantly inhibits the activity of the interferon-stimulated response element promoter and downregulates the transcription of interferon-stimulated genes. Further research revealed that 3D interacts with STAT2, hinders its phosphorylation, and inhibits its nuclear translocation, thereby blocking the activation of the JAK-STAT signaling pathway. Collectively, these findings elucidate a novel mechanism by which FMDV 3D polymerase, acting as an inhibitor, targets STAT2 to suppress IFN signaling and antagonize the host antiviral immune response. This will provide insights for the development of future anti-FMDV strategies.
{"title":"Foot-and-mouth disease virus 3D polymerase antagonizes the interferon signaling pathway by blocking STAT2 nuclear translocation","authors":"Kangli Li , Boning Zhu , Shuo Wang , Xiangle Zhang , Xiaodan Wen , Weijun Cao , Guoliang Zhu , Haixue Zheng , Fan Yang , Zixiang Zhu","doi":"10.1016/j.virusres.2025.199671","DOIUrl":"10.1016/j.virusres.2025.199671","url":null,"abstract":"<div><div>Foot-and-mouth disease virus (FMDV) is the etiological agent of foot-and-mouth disease (FMD), which is highly contagious and extremely destructive in cloven-hoofed animals. Previous studies have shown that FMDV strongly suppress the innate immune response, and the research mainly focused on FMDV 3C and L proteinase. However, the role of FMDV 3D polymerase, an RNA-dependent RNA polymerase (RdRp), in inhibiting the IFN signaling pathway remains unclear. In this study, for the first time, we demonstrate that the highly conserved 3D polymerase of FMDV inhibits the activation of the JAK-STAT signaling pathway by targeting STAT2. Mechanistically, FMDV 3D significantly inhibits the activity of the interferon-stimulated response element promoter and downregulates the transcription of interferon-stimulated genes. Further research revealed that 3D interacts with STAT2, hinders its phosphorylation, and inhibits its nuclear translocation, thereby blocking the activation of the JAK-STAT signaling pathway. Collectively, these findings elucidate a novel mechanism by which FMDV 3D polymerase, acting as an inhibitor, targets STAT2 to suppress IFN signaling and antagonize the host antiviral immune response. This will provide insights for the development of future anti-FMDV strategies.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"363 ","pages":"Article 199671"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.virusres.2025.199660
I-Na Lu , Claude P. Muller , Feng Q. HeFeng
{"title":"Corrigendum to “Applying next-generation sequencing to unravel the mutational landscape in viral quasispecies” [Virus Research, 283 (2020) 197963]","authors":"I-Na Lu , Claude P. Muller , Feng Q. HeFeng","doi":"10.1016/j.virusres.2025.199660","DOIUrl":"10.1016/j.virusres.2025.199660","url":null,"abstract":"","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199660"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.virusres.2025.199667
Liaofu Luo , Jun Lv
Predicting the future evolutionary trajectory of SARS-CoV-2 remains a critical challenge, particularly due to the pivotal role of spike protein mutations. It is therefore essential to develop evolutionary models capable of continuously integrating new experimental data. In this study, we employ a cladogram algorithm that incorporates established assumptions for mutant representation — using both four-letter and two-letter formats — along with an n-mer distance algorithm to construct a cladogenetic tree of SARS-CoV-2 mutations. This tree accurately captures the observed changes across macro-lineages. We introduce a stochastic method for generating new strains on this tree based on spike protein mutations. For a given set A of existing mutation sites, we define a set X comprising x randomly generated mutation sites on the spike protein. The intersection of A and X, denoted as set Y, contains y sites. Our analysis indicates that the position of a generated strain on the tree is primarily determined by x. Through large-scale stochastic sampling, we predict the emergence of new macro-lineages. As x increases, the dominance among macro-lineages shifts: lineage O surpasses N, P surpasses O, and eventually Q surpasses P. We identify threshold values of x that delineate transitions between these macro-lineages. Furthermore, we propose an algorithm for predicting the timeline of macro-lineage emergence. In conclusion, our findings demonstrate that SARS-CoV-2 evolution adheres to statistical principles: the emergence of new strains can be driven by randomly generated spike protein sites, and large-scale stochastic sampling reveals evolutionary patterns underlying the rise of distinct macro-lineages.
{"title":"Stochastic mutation as a mechanism for the emergence of SARS-CoV-2 new variants","authors":"Liaofu Luo , Jun Lv","doi":"10.1016/j.virusres.2025.199667","DOIUrl":"10.1016/j.virusres.2025.199667","url":null,"abstract":"<div><div>Predicting the future evolutionary trajectory of SARS-CoV-2 remains a critical challenge, particularly due to the pivotal role of spike protein mutations. It is therefore essential to develop evolutionary models capable of continuously integrating new experimental data. In this study, we employ a cladogram algorithm that incorporates established assumptions for mutant representation — using both four-letter and two-letter formats — along with an <em>n</em>-mer distance algorithm to construct a cladogenetic tree of SARS-CoV-2 mutations. This tree accurately captures the observed changes across macro-lineages. We introduce a stochastic method for generating new strains on this tree based on spike protein mutations. For a given set <em>A</em> of existing mutation sites, we define a set <em>X</em> comprising <em>x</em> randomly generated mutation sites on the spike protein. The intersection of <em>A</em> and <em>X</em>, denoted as set <em>Y</em>, contains <em>y</em> sites. Our analysis indicates that the position of a generated strain on the tree is primarily determined by <em>x</em>. Through large-scale stochastic sampling, we predict the emergence of new macro-lineages. As <em>x</em> increases, the dominance among macro-lineages shifts: lineage O surpasses N, P surpasses O, and eventually Q surpasses P. We identify threshold values of <em>x</em> that delineate transitions between these macro-lineages. Furthermore, we propose an algorithm for predicting the timeline of macro-lineage emergence. In conclusion, our findings demonstrate that SARS-CoV-2 evolution adheres to statistical principles: the emergence of new strains can be driven by randomly generated spike protein sites, and large-scale stochastic sampling reveals evolutionary patterns underlying the rise of distinct macro-lineages.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199667"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-16DOI: 10.1016/j.virusres.2025.199665
Abbas Khan , Anwar Mohammad , Fahad M. Alshabrmi , Eid A. Alatawi , Muhammad Junaid , Abdelali Agouni
Human metapneumovirus (HMPV), a current escalating health issue, causes respiratory complications in young children, the elderly, and immunocompromised individuals. To date, no specific treatment is available; thus, to support vaccine and therapeutic development, we present HMPV-TherRes: a specialized database for HMPV research. This platform integrates a wealth of genomic, proteomic, structural, and immunological data, as well as target-specific drugs, RNA-based therapeutics, and CRISPR-based designs, offering an invaluable resource for advancing both basic and clinical research. The database integrates data generated through state-of-the-art and AI-powered algorithms. The database hosts 618 annotated genomes from various parts of the world, along with protein information, including their physicochemical properties, and experimentally derived or AlphaFold-predicted 3D structures. Moreover, immune resources are a central feature, encompassing detailed information on the predicted and experimentally reported cytotoxic T lymphocyte (CTL) epitopes, helper T lymphocyte (HTL) epitopes (IFN ±), and B-cell epitopes. Additionally, it includes curated datasets, multi-epitope vaccines, and mRNA-based vaccine candidates, underscoring its utility in vaccine design and development. The database also provides data on different drugs targeting hMPV, along with extensive RNA-therapeutic resources, such as siRNAs and miRNAs, which are instrumental in gene-silencing applications. Further expanding its scope, HMPV-TherRes includes CRISPR-based sgRNA designs for both Cas9 and Cas13, enabling targeted genome editing and regulation of the transcriptome. HMPV-TherRes is a versatile repository bridging experimental and computational studies, consolidating diverse resources to support vaccine design, RNA therapeutics, and drug development. It advances understanding of hMPV biology, accelerating efforts to combat the pathogen. This centralized, user-friendly platform represents a significant advancement in virology, enabling researchers to develop novel interventions against HMPV. The database can be accessed through: https://ddd.agounikhanlabs.com/hmpvetherpresdb/index.php.
{"title":"HMPV-TherResDB: Comprehensive human metapneumovirus (HMPV) database for sequence-structure annotations, vaccine resources, and therapeutics research","authors":"Abbas Khan , Anwar Mohammad , Fahad M. Alshabrmi , Eid A. Alatawi , Muhammad Junaid , Abdelali Agouni","doi":"10.1016/j.virusres.2025.199665","DOIUrl":"10.1016/j.virusres.2025.199665","url":null,"abstract":"<div><div>Human metapneumovirus (HMPV), a current escalating health issue, causes respiratory complications in young children, the elderly, and immunocompromised individuals. To date, no specific treatment is available; thus, to support vaccine and therapeutic development, we present HMPV-TherRes: a specialized database for HMPV research. This platform integrates a wealth of genomic, proteomic, structural, and immunological data, as well as target-specific drugs, RNA-based therapeutics, and CRISPR-based designs, offering an invaluable resource for advancing both basic and clinical research. The database integrates data generated through state-of-the-art and AI-powered algorithms. The database hosts 618 annotated genomes from various parts of the world, along with protein information, including their physicochemical properties, and experimentally derived or AlphaFold-predicted 3D structures. Moreover, immune resources are a central feature, encompassing detailed information on the predicted and experimentally reported cytotoxic T lymphocyte (CTL) epitopes, helper T lymphocyte (HTL) epitopes (IFN ±), and B-cell epitopes. Additionally, it includes curated datasets, multi-epitope vaccines, and mRNA-based vaccine candidates, underscoring its utility in vaccine design and development. The database also provides data on different drugs targeting hMPV, along with extensive RNA-therapeutic resources, such as siRNAs and miRNAs, which are instrumental in gene-silencing applications. Further expanding its scope, HMPV-TherRes includes CRISPR-based sgRNA designs for both Cas9 and Cas13, enabling targeted genome editing and regulation of the transcriptome. HMPV-TherRes is a versatile repository bridging experimental and computational studies, consolidating diverse resources to support vaccine design, RNA therapeutics, and drug development. It advances understanding of hMPV biology, accelerating efforts to combat the pathogen. This centralized, user-friendly platform represents a significant advancement in virology, enabling researchers to develop novel interventions against HMPV. The database can be accessed through: <span><span>https://ddd.agounikhanlabs.com/hmpvetherpresdb/index.php</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"363 ","pages":"Article 199665"},"PeriodicalIF":2.7,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145551137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1016/j.virusres.2025.199664
Madeline I. Petrusic, Sarah K. McLean, Enzo A. Palombo
Numerous reports have revealed that the bacterium Vibrio parahaemolyticus is responsible for significant economic losses in aquaculture and poses a threat to public health. In search of a sustainable biocontrol agent against V. parahaemolyticus, two lytic and novel bacteriophages, VpP1 and VpP2, were characterised. Both phages exhibited broad host ranges, lysing 13/16 V. parahaemolyticus strains. Phages were imaged by transmission electron microscopy, and analysis revealed that both phages exhibit morphology consistent with members of the class Caudoviricetes. Both phages inhibited the growth of their respective host bacterium with a high multiplicity of infection. All treated cultures had a substantial reduction in viability compared to non-treated cultures. One-step growth curve analysis revealed a latent period of approximately 22 min for both phages. The burst sizes were calculated as 10.2 PFU/mL, and 7.3 PFU/mL for VpP1 and VpP2, respectively. Stability determination assays revealed both phages could withstand a broad salinity range (1 to 20 %), pH levels (3.0–10.0), temperatures (-20 to 60 °C) and sodium hydrochlorite levels (3 to 10 mg/mL). Phages VpP1 and VpP2 could withstand direct UV light for 4 and 5 min, respectively. Next-generations sequencing revealed that VpP1 (63,510 bp) and VpP2 (64,298 bp) did not contain known virulence, antibiotic-resistance or lysogenic genes, highlighting their capability to be used as biocontrol agents. Phylogenetic analysis based on the major head protein revealed that VpP1 and VpP2 were categorised into the newly described Mardecavirus genus. The results suggest VpP1 and VpP2 have several beneficial qualities for future use as biocontrol agents. Further study is still required to determine their efficiency within food applications.
{"title":"Characterisation of newly identified vibriophages and their potential application in the biocontrol of Vibrio parahaemolyticus to enhance safety in aquaculture","authors":"Madeline I. Petrusic, Sarah K. McLean, Enzo A. Palombo","doi":"10.1016/j.virusres.2025.199664","DOIUrl":"10.1016/j.virusres.2025.199664","url":null,"abstract":"<div><div>Numerous reports have revealed that the bacterium <em>Vibrio parahaemolyticus</em> is responsible for significant economic losses in aquaculture and poses a threat to public health. In search of a sustainable biocontrol agent against <em>V. parahaemolyticus</em>, two lytic and novel bacteriophages, VpP1 and VpP2, were characterised. Both phages exhibited broad host ranges, lysing 13/16 V<em>. parahaemolyticus</em> strains. Phages were imaged by transmission electron microscopy, and analysis revealed that both phages exhibit morphology consistent with members of the class <em>Caudoviricetes</em>. Both phages inhibited the growth of their respective host bacterium with a high multiplicity of infection. All treated cultures had a substantial reduction in viability compared to non-treated cultures. One-step growth curve analysis revealed a latent period of approximately 22 min for both phages. The burst sizes were calculated as 10.2 PFU/mL, and 7.3 PFU/mL for VpP1 and VpP2, respectively. Stability determination assays revealed both phages could withstand a broad salinity range (1 to 20 %), pH levels (3.0–10.0), temperatures (-20 to 60 °C) and sodium hydrochlorite levels (3 to 10 mg/mL). Phages VpP1 and VpP2 could withstand direct UV light for 4 and 5 min, respectively. Next-generations sequencing revealed that VpP1 (63,510 bp) and VpP2 (64,298 bp) did not contain known virulence, antibiotic-resistance or lysogenic genes, highlighting their capability to be used as biocontrol agents. Phylogenetic analysis based on the major head protein revealed that VpP1 and VpP2 were categorised into the newly described <em>Mardecavirus</em> genus. The results suggest VpP1 and VpP2 have several beneficial qualities for future use as biocontrol agents. Further study is still required to determine their efficiency within food applications.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"362 ","pages":"Article 199664"},"PeriodicalIF":2.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145533840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}