Pub Date : 2025-09-18DOI: 10.1016/j.virusres.2025.199633
Zoltán Vokó , Gergő Túri , Beatrix Oroszi , Éva Belicza , Tamás Kováts , Veronika Müller , János Réthelyi , Attila Szijártó , Tamás Masszi , István Takács , János Gál , Zsolt Göböl , Attila Szabó , Csaba Varga , Dávid Becker , Béla Merkely
COVID-19 vaccines reduce hospitalization risk, but data on severe outcomes are limited. We analyzed the impact of COVID-19 vaccination on severe outcomes in hospitalized patients in Hungary during the pre-Omicron era, addressing a regional knowledge gap. This retrospective study included hospitalized patients with PCR-confirmed COVID-19 (March 2020 – December 2021) who were categorized as unvaccinated, primary immunized, or booster-vaccinated. Outcomes included oxygen therapy, ventilation types, ECMO, and death, with the most severe outcome as the primary outcome and individual outcomes as secondary measures. Polytomous logistic regression calculated relative risk ratios for the primary outcome and COVID-19 vaccination status, while logistic regression estimated odds ratios for individual outcomes. During the study, 7575 patients were hospitalized with PCR-confirmed COVID-19: 6420 (84.8 %) were unvaccinated, 1016 (13.4 %) received a primary vaccination series, and 139 (1.8 %) had received a booster dose. COVID-19 vaccination reduced the risk of both invasive ventilation and in-hospital death as the most severe outcome by 50 % within 12 months (relative risk ratio [RRR]: 0.52, 95 % CI: 0.30–0.89; 0.50, 95 % CI: 0.41–0.61). Booster doses within six months decreased the risk of in-hospital death to a similar extent (RRR 0.46, 95 % CI: 0.30–0.72). Primary and booster vaccination reduced the risk of progression to severe outcomes in hospitalized COVID-19 patients.
{"title":"Association between COVID-19 vaccination and progression to severe outcomes in hospitalized COVID-19 patients in Hungary during the pre-Omicron era of the COVID-19 pandemic","authors":"Zoltán Vokó , Gergő Túri , Beatrix Oroszi , Éva Belicza , Tamás Kováts , Veronika Müller , János Réthelyi , Attila Szijártó , Tamás Masszi , István Takács , János Gál , Zsolt Göböl , Attila Szabó , Csaba Varga , Dávid Becker , Béla Merkely","doi":"10.1016/j.virusres.2025.199633","DOIUrl":"10.1016/j.virusres.2025.199633","url":null,"abstract":"<div><div>COVID-19 vaccines reduce hospitalization risk, but data on severe outcomes are limited. We analyzed the impact of COVID-19 vaccination on severe outcomes in hospitalized patients in Hungary during the pre-Omicron era, addressing a regional knowledge gap. This retrospective study included hospitalized patients with PCR-confirmed COVID-19 (March 2020 – December 2021) who were categorized as unvaccinated, primary immunized, or booster-vaccinated. Outcomes included oxygen therapy, ventilation types, ECMO, and death, with the most severe outcome as the primary outcome and individual outcomes as secondary measures. Polytomous logistic regression calculated relative risk ratios for the primary outcome and COVID-19 vaccination status, while logistic regression estimated odds ratios for individual outcomes. During the study, 7575 patients were hospitalized with PCR-confirmed COVID-19: 6420 (84.8 %) were unvaccinated, 1016 (13.4 %) received a primary vaccination series, and 139 (1.8 %) had received a booster dose. COVID-19 vaccination reduced the risk of both invasive ventilation and in-hospital death as the most severe outcome by 50 % within 12 months (relative risk ratio [RRR]: 0.52, 95 % CI: 0.30–0.89; 0.50, 95 % CI: 0.41–0.61). Booster doses within six months decreased the risk of in-hospital death to a similar extent (RRR 0.46, 95 % CI: 0.30–0.72). Primary and booster vaccination reduced the risk of progression to severe outcomes in hospitalized COVID-19 patients.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199633"},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102721","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 : 2025-09-11DOI: 10.1016/j.virusres.2025.199630
Jehad Zuhair Tayyeb , Maria Karolaynne da Silva , Aamal A. Al-Mutairi , Hanan M. Alharbi , Alaa A. Khojah , Imren Bayıl , Abdullah Yahya Abdullah Alzahrani , Zsolt Tóth , Jonas Ivan Nobre Oliveira , Magdi E.A. Zaki
Zika virus (ZIKV) infection remains a global health threat with no approved antivirals or vaccines to date, creating an urgent need for therapeutics targeting ZIKV. The viral envelope (E) protein is critical for host cell entry and represents a validated target for antiviral intervention. Here, we aimed to identify natural flavonoid compounds capable of inhibiting the ZIKV E protein using a dual-phase in silico screening strategy. First, we performed density functional theory (DFT) calculations to optimize the structures of nine candidate flavonoids and obtain quantum chemical descriptors (electronic properties); we also evaluated their drug-likeness and ADMET profiles. Second, we conducted molecular docking of these optimized flavonoids to the E protein, followed by hybrid quantum mechanics/molecular mechanics (QM/MM) refinement and 100 ns molecular dynamics (MD) simulations with principal component analysis (PCA) and MM-PBSA binding free energy calculations to assess binding interactions and complex stability. Docking identified quercetin, pinocembrin, and naringenin as the top binders, with binding energies of –8.3, –8.1, and –8.0 kcal/mol, respectively. These lead flavonoids also exhibited favorable pharmacokinetic properties, including high predicted gastrointestinal absorption, efficient clearance, and minimal toxicity risk (no carcinogenic or organ-specific alerts). Notably, pinocembrin’s complex demonstrated the greatest stability throughout a 100 ns MD simulation, maintaining a tightly bound conformation. In conclusion, quercetin, pinocembrin, and naringenin emerge as promising ZIKV E protein inhibitors with robust target engagement and favorable drug-like profiles. Their significant translational potential as antiviral candidates warrants further in vitro and in vivo studies to confirm efficacy and safety.
{"title":"Evaluation of Potential Inhibitors of Zika Virus Envelope Protein Through Molecular Docking and Molecular Dynamics Simulation","authors":"Jehad Zuhair Tayyeb , Maria Karolaynne da Silva , Aamal A. Al-Mutairi , Hanan M. Alharbi , Alaa A. Khojah , Imren Bayıl , Abdullah Yahya Abdullah Alzahrani , Zsolt Tóth , Jonas Ivan Nobre Oliveira , Magdi E.A. Zaki","doi":"10.1016/j.virusres.2025.199630","DOIUrl":"10.1016/j.virusres.2025.199630","url":null,"abstract":"<div><div>Zika virus (ZIKV) infection remains a global health threat with no approved antivirals or vaccines to date, creating an urgent need for therapeutics targeting ZIKV. The viral envelope (E) protein is critical for host cell entry and represents a validated target for antiviral intervention. Here, we aimed to identify natural flavonoid compounds capable of inhibiting the ZIKV E protein using a dual-phase <em>in silico</em> screening strategy. First, we performed density functional theory (DFT) calculations to optimize the structures of nine candidate flavonoids and obtain quantum chemical descriptors (electronic properties); we also evaluated their drug-likeness and ADMET profiles. Second, we conducted molecular docking of these optimized flavonoids to the E protein, followed by hybrid quantum mechanics/molecular mechanics (QM/MM) refinement and 100 ns molecular dynamics (MD) simulations with principal component analysis (PCA) and MM-PBSA binding free energy calculations to assess binding interactions and complex stability. Docking identified quercetin, pinocembrin, and naringenin as the top binders, with binding energies of –8.3, –8.1, and –8.0 kcal/mol, respectively. These lead flavonoids also exhibited favorable pharmacokinetic properties, including high predicted gastrointestinal absorption, efficient clearance, and minimal toxicity risk (no carcinogenic or organ-specific alerts). Notably, pinocembrin’s complex demonstrated the greatest stability throughout a 100 ns MD simulation, maintaining a tightly bound conformation. In conclusion, quercetin, pinocembrin, and naringenin emerge as promising ZIKV E protein inhibitors with robust target engagement and favorable drug-like profiles. Their significant translational potential as antiviral candidates warrants further <em>in vitro</em> and <em>in vivo</em> studies to confirm efficacy and safety.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"361 ","pages":"Article 199630"},"PeriodicalIF":2.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058609","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 : 2025-09-11DOI: 10.1016/j.virusres.2025.199628
Chu-Fan Cheng , Hsiang-Chieh Chuang , Yu-Shen Lai
{"title":"Corrigendum to ‘Characterization and antibody preparation of the gene products of grouper iridovirus ORF120L’ [Virus Research 360 (2025) 199625]","authors":"Chu-Fan Cheng , Hsiang-Chieh Chuang , Yu-Shen Lai","doi":"10.1016/j.virusres.2025.199628","DOIUrl":"10.1016/j.virusres.2025.199628","url":null,"abstract":"","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199628"},"PeriodicalIF":2.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055942","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 : 2025-09-05DOI: 10.1016/j.virusres.2025.199629
Santhamani Ramasamy , Felipe Bustamante , Lindsey C. LaBella , Stephen D. Cole , Jay Armstrong , David L. Thompson , John M. Hardham , Suresh V. Kuchipudi , Deepanker Tewari
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is capable of infecting multiple species through human-to-animal spillover. Human to animal spillovers have been documented both in domestic and wild animal species. Due to close contact in shared households, pet dogs may be at increased risk for contracting the SARS-CoV-2 virus from infected individuals in the same household. In this study, we have analyzed serum samples from dogs (n=196) from Pennsylvania during 2021-2022 for the presence of SARS-CoV-2 specific antibodies. The dogs in this analysis included those that were exposed to individuals of the household, who had history of recent SARS-CoV-2 infection, and from dogs with no known history of potential exposure to SARS-CoV-2. Our analysis found a significantly higher seroprevalence (68 %) among the dogs with exposure to SARS-CoV-2 infection from individuals from COVID-19 positive household compared to other dogs. Our study found the overall seroprevalence of 12.24 % among dogs as determined using a surrogate virus neutralization test (sVNT). All sera that were positive by sVNT were also positive by pseudovirus neutralization test (pVNT) except for sera from one dog, likely due to a lower antibody response. The antibody titers using the panel of spike pseudoviruses in pVNT test showed higher titers against the Delta, Gamma and Alpha variants compared to Omicron. We also tested the diagnostic capabilities of a lateral flow assay (LFA) developed by Zoetis by comparing it to sVNT and pVNT. The LFA showed sensitivity and specificity of 85 % compared to sVNT and 75 % compared to the pVNT indicating its potential for field use. These findings provide serological evidence of SARS-CoV-2 spillover to pet dogs and underscore the importance of continued surveillance in companion animals as part of a One Health approach, especially as new viral variants continue to emerge.
{"title":"Spillover of SARS-CoV-2 to domestic dogs in COVID-19–positive households: A one health surveillance study","authors":"Santhamani Ramasamy , Felipe Bustamante , Lindsey C. LaBella , Stephen D. Cole , Jay Armstrong , David L. Thompson , John M. Hardham , Suresh V. Kuchipudi , Deepanker Tewari","doi":"10.1016/j.virusres.2025.199629","DOIUrl":"10.1016/j.virusres.2025.199629","url":null,"abstract":"<div><div>The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is capable of infecting m<em>ultiple species</em> through human-to-animal spillover. Human to animal spillovers have been documented both in domestic and wild animal species. Due to close contact in shared households, pet dogs may be at increased risk for contracting the SARS-CoV-2 virus from infected individuals in the same household. In this study, we have analyzed serum samples from dogs (<em>n</em>=196) from Pennsylvania during 2021-2022 for the presence of SARS-CoV-2 specific antibodies. The dogs in this analysis included those that were exposed to individuals of the household, who had history of recent SARS-CoV-2 infection, and from dogs with no known history of potential exposure to SARS-CoV-2. Our analysis found a significantly higher seroprevalence (68 %) among the dogs with exposure to SARS-CoV-2 infection from individuals from COVID-19 positive household compared to other dogs. Our study found the overall seroprevalence of 12.24 % among dogs as determined using a surrogate virus neutralization test (sVNT). All sera that were positive by sVNT were also positive by pseudovirus neutralization test (pVNT) except for sera from one dog, likely due to a lower antibody response. The antibody titers using the panel of spike pseudoviruses in pVNT test showed higher titers against the Delta, Gamma and Alpha variants compared to Omicron. We also tested the diagnostic capabilities of a lateral flow assay (LFA) developed by Zoetis by comparing it to sVNT and pVNT. The LFA showed sensitivity and specificity of 85 % compared to sVNT and 75 % compared to the pVNT indicating its potential for field use. These findings provide serological evidence of SARS-CoV-2 spillover to pet dogs and underscore the importance of continued surveillance in companion animals as part of a One Health approach, especially as new viral variants continue to emerge.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199629"},"PeriodicalIF":2.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016221","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 : 2025-09-02DOI: 10.1016/j.virusres.2025.199627
Li Xiong , Lingting Wang , He Liu , Yufei He , Hong Wang , Fan Bai
Introduction
Osteoporosis is a major risk factor for fractures, yet the contribution of immune responses to its pathogenesis remains poorly understood. This study investigates whether common viral infections, including Epstein–Barr virus (EBV), human herpesvirus 6 (HHV-6), and varicella-zoster virus (VZV), contribute to osteoporosis through immune-mediated pathways.
Methods
We performed two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) summary data and complemented this with observational analyses from the NHANES 2003–2004 cycle. Antibody responses to EBV, HHV-6, and VZV were examined for potential causal effects on bone mineral density (BMD) at key skeletal sites.
Results
MR analyses indicated that stronger antibody responses to EBV, HHV-6, and VZV were associated with reduced BMD, particularly at the lumbar spine and femoral neck (OR = 1.18, 95 % CI: 1.02–1.36, p = 0.040). Subgroup analyses suggested more pronounced reductions among young men with EBV and elderly women with VZV. Sensitivity tests supported the robustness of these findings.
Conclusions
Our findings suggest that common herpesvirus infections may contribute to bone loss via immune-mediated mechanisms, especially in vulnerable subgroups. These results provide epidemiological support for a viral–immune link in osteoporosis and underscore the need for mechanistic and longitudinal studies to clarify underlying pathways and guide future preventive strategies.
骨质疏松症是骨折的主要危险因素，然而免疫反应在其发病机制中的作用仍然知之甚少。本研究探讨了包括eb病毒（EBV）、人类疱疹病毒6 （HHV-6）和水痘带状疱疹病毒（VZV）在内的常见病毒感染是否通过免疫介导的途径导致骨质疏松症。方法：我们使用全基因组关联研究（GWAS）汇总数据进行了两样本孟德尔随机化（MR），并辅以NHANES 2003-2004周期的观察性分析。研究人员检测了EBV、HHV-6和VZV抗体应答对关键骨骼部位骨矿物质密度（BMD）的潜在因果影响。结果：MR分析表明，EBV、HHV-6和VZV抗体反应较强与骨密度降低相关，尤其是腰椎和股骨颈（OR = 1.18,95% CI: 1.02-1.36, p = 0.040）。亚组分析显示，年轻男性EBV患者和老年女性VZV患者的减少更为明显。敏感性测试支持了这些发现的稳健性。结论：我们的研究结果表明，常见的疱疹病毒感染可能通过免疫介导的机制导致骨质流失，特别是在易感亚群中。这些结果为骨质疏松症的病毒免疫联系提供了流行病学支持，并强调了机制和纵向研究的必要性，以阐明潜在的途径并指导未来的预防策略。
{"title":"Immune-mediated bone loss: A Mendelian randomization and NHANES-based study of viral infections and osteoporosis","authors":"Li Xiong , Lingting Wang , He Liu , Yufei He , Hong Wang , Fan Bai","doi":"10.1016/j.virusres.2025.199627","DOIUrl":"10.1016/j.virusres.2025.199627","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoporosis is a major risk factor for fractures, yet the contribution of immune responses to its pathogenesis remains poorly understood. This study investigates whether common viral infections, including Epstein–Barr virus (EBV), human herpesvirus 6 (HHV-6), and varicella-zoster virus (VZV), contribute to osteoporosis through immune-mediated pathways.</div></div><div><h3>Methods</h3><div>We performed two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) summary data and complemented this with observational analyses from the NHANES 2003–2004 cycle. Antibody responses to EBV, HHV-6, and VZV were examined for potential causal effects on bone mineral density (BMD) at key skeletal sites.</div></div><div><h3>Results</h3><div>MR analyses indicated that stronger antibody responses to EBV, HHV-6, and VZV were associated with reduced BMD, particularly at the lumbar spine and femoral neck (OR = 1.18, 95 % CI: 1.02–1.36, <em>p</em> = 0.040). Subgroup analyses suggested more pronounced reductions among young men with EBV and elderly women with VZV. Sensitivity tests supported the robustness of these findings.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that common herpesvirus infections may contribute to bone loss via immune-mediated mechanisms, especially in vulnerable subgroups. These results provide epidemiological support for a viral–immune link in osteoporosis and underscore the need for mechanistic and longitudinal studies to clarify underlying pathways and guide future preventive strategies.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199627"},"PeriodicalIF":2.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001101","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 : 2025-09-01Epub Date: 2025-08-05DOI: 10.1016/j.virusres.2025.199613
Pier-Angelo Tovo, Angelo Armandi, Mauro Bruno, Gian Paolo Caviglia, Paola Montanari, Demis Pitoni, Cristina Calvi, Simone Frara, Eleonora Dileo, Stefano Gambarino, Ilaria Galliano, Davide Giuseppe Ribaldone, Massimiliano Bergallo
Celiac disease (CeD) is a disorder due to abnormal immune response to gluten protein in individuals with predisposing genotypes. Its origin is not fully understood. Human endogenous retroviruses (HERVs) derive from ancestral infections of germinal cells and represent 8 % of the human DNA. They are mostly inactive, but some can be activated. Their aberrant expressions are associated with inflammatory and immune-mediated diseases. HERV transcription is modulated by TRIM28 and SETDB1, which are also directly implicated in epigenetic processes and modulation of the immune response. We reported HERV overexpressions in CeD children at diagnosis. In the current prospective study, using a PCR real-time Taqman amplification assay, we explored the transcription levels of HERV-H-pol, -HERV-K-pol, and HERV-W-pol, of syncytin 1 (SYN1), SYN2, and HERV-W-env, as well as of TRIM28 and SETDB1 in the whole blood from 51 adults with CeD after years of good compliance with gluten-free diet (GFD) as compared to healthy controls (HC) of similar age. The transcriptional levels of every HERV and of TRIM28/SETDB1 were significantly higher in CeD patients than in HC (constantly with p < 0.0001). Positive correlations were found between the RNA levels of TRIM28 or SETDB1 and HERVs in CeD patients. The upregulation of HERVs, TRIM28, and SETDB1 and their positive correlations are suggestive clues of their contribution to the pathophysiology of CeD and might justify the persistent risk of developing, despite GFD, autoimmune diseases, neuropsychiatric disturbances, and cancers, all disorders characterized by enhanced HERV expressions and epigenetic alterations.
{"title":"Adults with celiac disease exhibit overexpression of endogenous retroviruses, TRIM28, and SETDB1 despite gluten-free diet.","authors":"Pier-Angelo Tovo, Angelo Armandi, Mauro Bruno, Gian Paolo Caviglia, Paola Montanari, Demis Pitoni, Cristina Calvi, Simone Frara, Eleonora Dileo, Stefano Gambarino, Ilaria Galliano, Davide Giuseppe Ribaldone, Massimiliano Bergallo","doi":"10.1016/j.virusres.2025.199613","DOIUrl":"10.1016/j.virusres.2025.199613","url":null,"abstract":"<p><p>Celiac disease (CeD) is a disorder due to abnormal immune response to gluten protein in individuals with predisposing genotypes. Its origin is not fully understood. Human endogenous retroviruses (HERVs) derive from ancestral infections of germinal cells and represent 8 % of the human DNA. They are mostly inactive, but some can be activated. Their aberrant expressions are associated with inflammatory and immune-mediated diseases. HERV transcription is modulated by TRIM28 and SETDB1, which are also directly implicated in epigenetic processes and modulation of the immune response. We reported HERV overexpressions in CeD children at diagnosis. In the current prospective study, using a PCR real-time Taqman amplification assay, we explored the transcription levels of HERV-H-pol, -HERV-K-pol, and HERV-W-pol, of syncytin 1 (SYN1), SYN2, and HERV-W-env, as well as of TRIM28 and SETDB1 in the whole blood from 51 adults with CeD after years of good compliance with gluten-free diet (GFD) as compared to healthy controls (HC) of similar age. The transcriptional levels of every HERV and of TRIM28/SETDB1 were significantly higher in CeD patients than in HC (constantly with p < 0.0001). Positive correlations were found between the RNA levels of TRIM28 or SETDB1 and HERVs in CeD patients. The upregulation of HERVs, TRIM28, and SETDB1 and their positive correlations are suggestive clues of their contribution to the pathophysiology of CeD and might justify the persistent risk of developing, despite GFD, autoimmune diseases, neuropsychiatric disturbances, and cancers, all disorders characterized by enhanced HERV expressions and epigenetic alterations.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":" ","pages":"199613"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.virusres.2025.199626
Tian Gong , Xuan Zhang , Haiyan Lin , Jing Li , Jiaqi Tao , Ting Zeng , Xinyi Ren , Zhiting Xie , Xiao Lei , Sufeng Zhang , Chengsheng Zhang
The ongoing mutation and evolution of SARS-CoV-2 have posed a severe threat to global health, and their functional impact remains to be further characterized. Here, we analyzed the selection pressure from 49 Omicron sub-strains at the gene and amino acid levels. We also examined the impact of mutations on the binding affinity between the receptor binding domain (RBD) and angiotensin-Converting Enzyme 2 (ACE2) and evaluated the immune escape ability of RBD responding to the monoclonal antibodies (mAbs) through molecular dynamics simulation on eight representative Omicron sub-variants (B.1.1.529, BA.2, XBB.1.5, BA.2.86, JN.1, KP.2, KP.3, and KP.3.1.1). We identified 12 positive selection mutation sites on the viral S protein, including 11 mutation sites in the N-terminal domain (NTD) and RBD regions. A large number of accumulated mutation sites led to an increase in the receptor binding affinity of B.1.1.529 and BA.2.86. In particular, the “saltatory” evolution of BA.2.86 reached to its maximum binding affinity. The E484K mutation exhibited the highest binding affinity in the BA.2.86 and its descendants. New mutation sites either did not affect the binding affinity (R346T, L455S and F456L) or decrease the affinity (K356T and Q493E), reflecting the fluctuation of total receptor binding force. Mutations and shortened conformational epitopes on RBD may mediate the immune escape in the variants of BA.2.86. Moreover, we revealed that the ABBV-47D11 monoclonal antibody could widely bind to the RBD mutation sites of various mutant strains. Our findings may help understand the evolution of SARS-CoV-2 variants and develop novel strategies against SARS-CoV-2 infection.
{"title":"Mutation profiling, evolution analysis, molecular dynamics simulation, and functional characterization of Omicron sub-strains","authors":"Tian Gong , Xuan Zhang , Haiyan Lin , Jing Li , Jiaqi Tao , Ting Zeng , Xinyi Ren , Zhiting Xie , Xiao Lei , Sufeng Zhang , Chengsheng Zhang","doi":"10.1016/j.virusres.2025.199626","DOIUrl":"10.1016/j.virusres.2025.199626","url":null,"abstract":"<div><div>The ongoing mutation and evolution of SARS-CoV-2 have posed a severe threat to global health, and their functional impact remains to be further characterized. Here, we analyzed the selection pressure from 49 Omicron sub-strains at the gene and amino acid levels. We also examined the impact of mutations on the binding affinity between the receptor binding domain (RBD) and angiotensin-Converting Enzyme 2 (ACE2) and evaluated the immune escape ability of RBD responding to the monoclonal antibodies (mAbs) through molecular dynamics simulation on eight representative Omicron sub-variants (B.1.1.529, BA.2, XBB.1.5, BA.2.86, JN.1, KP.2, KP.3, and KP.3.1.1). We identified 12 positive selection mutation sites on the viral S protein, including 11 mutation sites in the N-terminal domain (NTD) and RBD regions. A large number of accumulated mutation sites led to an increase in the receptor binding affinity of B.1.1.529 and BA.2.86. In particular, the “saltatory” evolution of BA.2.86 reached to its maximum binding affinity. The E484K mutation exhibited the highest binding affinity in the BA.2.86 and its descendants. New mutation sites either did not affect the binding affinity (R346T, L455S and F456L) or decrease the affinity (K356T and Q493E), reflecting the fluctuation of total receptor binding force. Mutations and shortened conformational epitopes on RBD may mediate the immune escape in the variants of BA.2.86. Moreover, we revealed that the ABBV-47D11 monoclonal antibody could widely bind to the RBD mutation sites of various mutant strains. Our findings may help understand the evolution of SARS-CoV-2 variants and develop novel strategies against SARS-CoV-2 infection.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199626"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970859","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 : 2025-09-01Epub Date: 2025-08-05DOI: 10.1016/j.virusres.2025.199614
Mia Miranti, Iqbal Nur Iskandar, Melanie Melanie, Desak Made Malini, Camelia Panatarani, I Made Joni, Dedat Prismantoro, Febri Doni, Ravindra Chandra Joshi, Wawan Hermawan
Helicoverpa armigera nucleopolyhedrovirus (HearNPV1) shows considerable potential as a sustainable biological control agent against insect pests. Enhancing its efficacy through formulation with appropriate carrier materials is critical for improving pest management strategies. This study evaluated the potential of chitosan and zeolite nanoparticles as delivery vehicles for HearNPV1, assessing their effects on mortality and lethal time in second-instar Spodoptera litura larvae. A single-factor randomized block design with three replications was used. The treatments consisted of HearNPV1 formulated with various concentrations (0.125 % to 0.5 %) of either chitosan or zeolite nanoparticles. Larval mortality and lethal time (LT) were recorded and analyzed using one-way ANOVA, with significant differences further assessed by Duncan's multiple range test (α=0.05). Results showed that formulating HearNPV1 with either chitosan or zeolite nanoparticles significantly increased larval mortality. Notably, even the lowest concentration tested (0.125 %) of both chitosan and zeolite nanoparticles achieved 66.67 % larval mortality within seven days post-infection. However, no significant differences in lethal time were observed among treatments, regardless of nanoparticle type or concentration. Larvae exposed to virus-nanoparticle formulations exhibited lethal times ranging from 3.0 to 4.67 days on average-similar to the duration observed in larvae infected with HearNPV1 alone. In conclusion, both chitosan and zeolite nanoparticles at 0.125 % concentrations effectively enhanced HearNPV1-induced mortality in S. litura larvae, although they did not shorten the time to death. These findings underscore the potential for nanoparticle-based HearNPV1 formulations to improve biological pest control, warranting further investigation into their practical application and mechanisms of action.
{"title":"Enhanced efficacy of Helicoverpa armigera nucleopolyhedrovirus against Spodoptera litura larvae using zeolite and chitosan nanoparticle formulations.","authors":"Mia Miranti, Iqbal Nur Iskandar, Melanie Melanie, Desak Made Malini, Camelia Panatarani, I Made Joni, Dedat Prismantoro, Febri Doni, Ravindra Chandra Joshi, Wawan Hermawan","doi":"10.1016/j.virusres.2025.199614","DOIUrl":"10.1016/j.virusres.2025.199614","url":null,"abstract":"<p><p>Helicoverpa armigera nucleopolyhedrovirus (HearNPV1) shows considerable potential as a sustainable biological control agent against insect pests. Enhancing its efficacy through formulation with appropriate carrier materials is critical for improving pest management strategies. This study evaluated the potential of chitosan and zeolite nanoparticles as delivery vehicles for HearNPV1, assessing their effects on mortality and lethal time in second-instar Spodoptera litura larvae. A single-factor randomized block design with three replications was used. The treatments consisted of HearNPV1 formulated with various concentrations (0.125 % to 0.5 %) of either chitosan or zeolite nanoparticles. Larval mortality and lethal time (LT) were recorded and analyzed using one-way ANOVA, with significant differences further assessed by Duncan's multiple range test (α=0.05). Results showed that formulating HearNPV1 with either chitosan or zeolite nanoparticles significantly increased larval mortality. Notably, even the lowest concentration tested (0.125 %) of both chitosan and zeolite nanoparticles achieved 66.67 % larval mortality within seven days post-infection. However, no significant differences in lethal time were observed among treatments, regardless of nanoparticle type or concentration. Larvae exposed to virus-nanoparticle formulations exhibited lethal times ranging from 3.0 to 4.67 days on average-similar to the duration observed in larvae infected with HearNPV1 alone. In conclusion, both chitosan and zeolite nanoparticles at 0.125 % concentrations effectively enhanced HearNPV1-induced mortality in S. litura larvae, although they did not shorten the time to death. These findings underscore the potential for nanoparticle-based HearNPV1 formulations to improve biological pest control, warranting further investigation into their practical application and mechanisms of action.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":" ","pages":"199614"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-08-07DOI: 10.1016/j.virusres.2025.199612
Jiajun Wu, Xiaohan Qian, Shi Bai, Lijuan Wu, Xian Zhao
Non-apoptotic programmed cell death (NAPCD) represents a diverse set of cell death mechanisms that differ from classical apoptosis and have recently gained attention in the context of viral infections. This review focuses on four key NAPCD types, including ferroptosis, cuproptosis, NETosis (neutrophil extracellular trap formation), and PANoptosis (a combination of pyroptosis, apoptosis, and necroptosis), and summarizes their distinct molecular pathways and roles during viral infections. We emphasize their functional relevance in SARS-CoV-2 infection, revealing how they significantly impact viral replication, host immune responses, and tissue damage. Furthermore, we explore the interaction between NAPCDs and specific immune responses. Specifically, ferroptosis influences macrophage polarization. Cuproptosis activates innate immunity via the cGAS-STING pathway. NETosis contributes to Th17 responses, and PANoptosis interacts with Th1, Th22, and Thαβ pathways. Understanding the interplay among these cell death pathways provides new insights into host-virus dynamics and uncovers potential therapeutic targets for viral diseases.
{"title":"Lesser-known non-apoptotic programmed cell death in viral infections.","authors":"Jiajun Wu, Xiaohan Qian, Shi Bai, Lijuan Wu, Xian Zhao","doi":"10.1016/j.virusres.2025.199612","DOIUrl":"10.1016/j.virusres.2025.199612","url":null,"abstract":"<p><p>Non-apoptotic programmed cell death (NAPCD) represents a diverse set of cell death mechanisms that differ from classical apoptosis and have recently gained attention in the context of viral infections. This review focuses on four key NAPCD types, including ferroptosis, cuproptosis, NETosis (neutrophil extracellular trap formation), and PANoptosis (a combination of pyroptosis, apoptosis, and necroptosis), and summarizes their distinct molecular pathways and roles during viral infections. We emphasize their functional relevance in SARS-CoV-2 infection, revealing how they significantly impact viral replication, host immune responses, and tissue damage. Furthermore, we explore the interaction between NAPCDs and specific immune responses. Specifically, ferroptosis influences macrophage polarization. Cuproptosis activates innate immunity via the cGAS-STING pathway. NETosis contributes to Th17 responses, and PANoptosis interacts with Th1, Th22, and Thαβ pathways. Understanding the interplay among these cell death pathways provides new insights into host-virus dynamics and uncovers potential therapeutic targets for viral diseases.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":" ","pages":"199612"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1016/j.virusres.2025.199625
Chu-Fan Cheng , Hsiang-Chieh Chuang , Yu-Shen Lai
Grouper iridovirus (GIV) is regarded as a prominent viral pathogen of grouper, particularly during the larval and juvenile stages. The aim of this study was to comprehensively characterize the GIV-120L gene during viral infection. The results of sequence analysis suggest that GIV-120L is a 1,470 bp gene encoding a Ranavirus-specific viral protein. Recombinant GIV-120L protein was purified using a nickel-affinity column, and its molecular weight was found to be 59.1 kDa. To obtain antibodies against GIV, mice were immunized with recombinant GIV-120L protein, the spleen was harvested 8 weeks later, and hybridoma testing was performed using Sp2/0 myeloma cells. Polyclonal and monoclonal antibodies against GIV-120L were obtained. To characterize GIV-120L gene expression, grouper kidney (GK) cells were infected with GIV using cycloheximide (CHX) and cytosine arabinoside (AraC). GIV-120L transcripts and protein were found at 12–30 h post infection (hpi) and 18–30 hpi, respectively. In addition, inhibition with CHX and AraC confirmed that GIV-120L was a late gene. Immunofluorescence staining using the antibodies produced in the study confirmed that GIV-120L protein is expressed at viral assembly sites at 24 hpi. The findings of this study provide functional characterization of the GIV-120L viral gene, enhance understanding of GIV assembly, and offer insights for GIV diagnostic applications.
{"title":"Characterization and antibody preparation of the gene products of grouper iridovirus ORF120L","authors":"Chu-Fan Cheng , Hsiang-Chieh Chuang , Yu-Shen Lai","doi":"10.1016/j.virusres.2025.199625","DOIUrl":"10.1016/j.virusres.2025.199625","url":null,"abstract":"<div><div>Grouper iridovirus (GIV) is regarded as a prominent viral pathogen of grouper, particularly during the larval and juvenile stages. The aim of this study was to comprehensively characterize the GIV-120L gene during viral infection. The results of sequence analysis suggest that GIV-120L is a 1,470 bp gene encoding a <em>Ranavirus</em>-specific viral protein. Recombinant GIV-120L protein was purified using a nickel-affinity column, and its molecular weight was found to be 59.1 kDa. To obtain antibodies against GIV, mice were immunized with recombinant GIV-120L protein, the spleen was harvested 8 weeks later, and hybridoma testing was performed using Sp2/0 myeloma cells. Polyclonal and monoclonal antibodies against GIV-120L were obtained. To characterize GIV-120L gene expression, grouper kidney (GK) cells were infected with GIV using cycloheximide (CHX) and cytosine arabinoside (AraC). GIV-120L transcripts and protein were found at 12–30 h post infection (hpi) and 18–30 hpi, respectively. In addition, inhibition with CHX and AraC confirmed that GIV-120L was a late gene. Immunofluorescence staining using the antibodies produced in the study confirmed that GIV-120L protein is expressed at viral assembly sites at 24 hpi. The findings of this study provide functional characterization of the GIV-120L viral gene, enhance understanding of GIV assembly, and offer insights for GIV diagnostic applications.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199625"},"PeriodicalIF":2.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912258","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}
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