Antiviral research最新文献_第3页

Truncated rotavirus VP4 proteins induce stronger protective immunity compared to P2 - VP8 in animal models 在动物模型中，截断的轮状病毒VP4蛋白比P2 - VP8蛋白诱导更强的保护性免疫。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-04-05 DOI: 10.1016/j.antiviral.2025.106156

Yaling Chen , Guoxing Luo , Feibo Song , Xuechun Wang , Shiyin Zhang , Shengxiang Ge , Tingdong Li , Jun Zhang , Ningshao Xia

{"title":"Truncated rotavirus VP4 proteins induce stronger protective immunity compared to P2 - VP8 in animal models","authors":"Yaling Chen , Guoxing Luo , Feibo Song , Xuechun Wang , Shiyin Zhang , Shengxiang Ge , Tingdong Li , Jun Zhang , Ningshao Xia","doi":"10.1016/j.antiviral.2025.106156","DOIUrl":"10.1016/j.antiviral.2025.106156","url":null,"abstract":"<div><div>Group A rotavirus (RVA) is the primary causative agent of acute gastroenteritis (AGE) in children under five years of age, resulting in over 120,000 deaths annually. In previous studies, we identified truncated VP4∗ as a potentially more promising vaccine candidate compared to VP8∗ and VP5∗. This study aimed to compare the immunogenicity and protective efficacy of VP4∗ and P2-VP8, the most advanced recombinant rotavirus vaccine undergoing phase 3 clinical trial in various animal models, including mice, guinea pigs, rabbits, and piglets. The results indicated that the binding antibodies and neutralizing antibodies induced by VP4∗ were significantly higher levels compared to P2-VP8. Immunization with VP4∗ provided 100 % protection for mice against challenges with EDIM and LLR strains. Additionally, we were intrigued to discover that the VP4∗ antibody not only inhibited virus adsorption but also prevented the virus from entering cells following pre-adsorption. In summary, VP4∗ demonstrates greater immunogenicity and protective efficacy compared to P2-VP8, making it a more promising candidate antigen for recombinant rotavirus vaccines.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"238 ","pages":"Article 106156"},"PeriodicalIF":4.5,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Salicylamide derivative JMX0312 protects immunosuppressed Syrian hamsters against adenovirus lethal challenge 水杨胺衍生物JMX0312保护免疫抑制的叙利亚仓鼠免受腺病毒致命攻击

IF 4.5 2区医学

Antiviral research Pub Date : 2025-04-02 DOI: 10.1016/j.antiviral.2025.106155

Marta Carretero-Ledesma , Jun Li , Javier Martín-Escolano , Soraya Herrera-Espejo , Jimin Xu , Haiying Chen , Caridad Díaz-Navarro , Jerónimo Pachón , Javier Sánchez-Céspedes , Jia Zhou , María Eugenia Pachón-Ibáñez

{"title":"Salicylamide derivative JMX0312 protects immunosuppressed Syrian hamsters against adenovirus lethal challenge","authors":"Marta Carretero-Ledesma , Jun Li , Javier Martín-Escolano , Soraya Herrera-Espejo , Jimin Xu , Haiying Chen , Caridad Díaz-Navarro , Jerónimo Pachón , Javier Sánchez-Céspedes , Jia Zhou , María Eugenia Pachón-Ibáñez","doi":"10.1016/j.antiviral.2025.106155","DOIUrl":"10.1016/j.antiviral.2025.106155","url":null,"abstract":"<div><div>Despite the fact that human adenovirus (HAdV) causes severe infections in immunosuppressed and immunocompetent individuals, especially in children, there is currently no specific treatment for these infections. Previously we reported a new salicylamide analogue, JMX0312, as a potent inhibitor of HAdV infection with low cytotoxicity <em>in vitro</em>. Here we evaluate the <em>in vivo</em> efficacy and safety of this molecule in the immunosuppressed Syrian hamster model of HAdV infection. JMX0312 administration at a dose of 6.25 mg/kg did not affect the body weight of the animals, and reduced the viral load in liver and blood in a similar way than cidofovir. Also, JMX0312 reduced the mortality of the animals, although in a lesser extent than cidofovir, a drug used to treat these infections that must be subject to rigorous monitoring due to its high toxicity and whose used is not approved in children. Our findings highlight the potential of this new antiviral agent for the treatment of HAdV infections, paving the way for future pre-clinical and clinical trial development towards a safer and more effective treatment against HAdV-associated infections.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"238 ","pages":"Article 106155"},"PeriodicalIF":4.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comprehensive preclinical characterization of IPB29, a pan-coronavirus fusion inhibitor under clinical trials 临床试验中泛冠状病毒融合抑制剂IPB29的临床前综合表征

IF 4.5 2区医学

Antiviral research Pub Date : 2025-03-28 DOI: 10.1016/j.antiviral.2025.106154

Yuanmei Zhu , Zhongcai Gao , Xiaoli Feng , Yue Hu , Nian Liu , Chao Liu , Qiaojiang Yang , Qingcui Zou , Minghua Li , Gengshen Song , Yuxian He

{"title":"Comprehensive preclinical characterization of IPB29, a pan-coronavirus fusion inhibitor under clinical trials","authors":"Yuanmei Zhu , Zhongcai Gao , Xiaoli Feng , Yue Hu , Nian Liu , Chao Liu , Qiaojiang Yang , Qingcui Zou , Minghua Li , Gengshen Song , Yuxian He","doi":"10.1016/j.antiviral.2025.106154","DOIUrl":"10.1016/j.antiviral.2025.106154","url":null,"abstract":"<div><div>IPB29 is a lipopeptide-based coronavirus fusion inhibitor with the potent, broad-spectrum antiviral activity, and it has already been advanced to phase III clinical trials for the treatment of SARS-CoV-2 infection. We recently reported its design strategy and initial preclinical characterization; herein, we focused on characterizing its efficacies against newly-emerged Omicron variants, as well as its chronic general toxicity, toxicokinetics, immunogenicity, and reproductive toxicity in animal models. As anticipated, IPB29 demonstrated improved activity in inhibiting JN.1 and KP.2 variants, effectively blocking cell fusion and pseudovirus infections. Nebulized inhalation of IPB29 exhibited high therapeutic efficacy against live BA.5 and EG.5.1 infections in Syrian hamsters. The 26-week toxicity studies revealed that nebulized IPB29 has a favorable safety profile, with well-characterized toxicokinetics in SD rats and Beagle dogs. Notably, short-term nebulization of IPB29 did not elicit anti-drug antibody (ADA) responses in either species. However, IPB29-specific antibodies were detected after long-term administration. Finally, a three-stage reproductive toxicity study in SD rats indicated that IPB29 had no significant toxic effects on fertility, embryo-fetal development, or the development of offspring. In summary, our findings demonstrate that IPB29 is a safe and effective SARS-CoV-2 inhibitor with promising potential for clinical applications.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106154"},"PeriodicalIF":4.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hijacking JAKis: JAK inhibitors as potential antiviral molecules, a mini review 劫持JAKis：作为潜在抗病毒分子的JAK抑制剂，综述。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-03-27 DOI: 10.1016/j.antiviral.2025.106153

Claudie Eber, Eloi R. Verrier

引用次数: 0

Overview on the management of herpes simplex virus infections: Current therapies and future directions 单纯疱疹病毒感染管理概述：当前疗法和未来方向。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-03-26 DOI: 10.1016/j.antiviral.2025.106152

Alexander Birkmann , Rob Saunders

{"title":"Overview on the management of herpes simplex virus infections: Current therapies and future directions","authors":"Alexander Birkmann , Rob Saunders","doi":"10.1016/j.antiviral.2025.106152","DOIUrl":"10.1016/j.antiviral.2025.106152","url":null,"abstract":"<div><h3>Introduction</h3><div>Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are highly prevalent, infecting approximately 64 % and 13 % of the world's population, respectively. Traditionally, HSV-1 has been associated with orofacial infections and HSV-2 with anogenital infections, but HSV-1 is increasingly the cause of genital infections. The clinical spectrum of HSV disease ranges from mild cold sores to severe conditions such as encephalitis or systemic infection, particularly in immunocompromised individuals and neonates.</div></div><div><h3>Areas covered</h3><div>Here we summarize the natural history, epidemiology, manifestations, and treatment options for HSV infections. Current treatments, such as acyclovir, target viral DNA polymerase but have limited efficacy and are susceptible to resistance, especially in immunosuppressed populations. Rescue therapies such as foscarnet exhibit limiting toxicity. Vaccine development has been challenging, and a cure for HSV infection remains distant. Gene therapy is still in its early stages, while novel drugs such as helicase primase inhibitors (HPIs) are emerging as a promising alternative, showing high efficacy and the potential to overcome resistance.</div></div><div><h3>Expert opinion</h3><div>HPIs represent a significant advance in HSV management. Their safety profile and novel mode of action may provide better viral suppression with a lower risk of resistance, offering hope for better control of the disease.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106152"},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tenofovir alafenamide promotes weight gain and impairs fatty acid metabolism-related signaling pathways in visceral fat tissue compared to tenofovir disoproxil fumarate 与富马酸替诺福韦二氧吡酯相比，替诺福韦阿拉那胺促进体重增加并损害内脏脂肪组织中脂肪酸代谢相关的信号通路

IF 4.5 2区医学

Antiviral research Pub Date : 2025-03-26 DOI: 10.1016/j.antiviral.2025.106151

Bryan Dulion , Arnold Z. Olali , Niyati Patel , Amber K. Virdi , Ankur Naqib , Jennillee Wallace , Ryan D. Ross

{"title":"Tenofovir alafenamide promotes weight gain and impairs fatty acid metabolism-related signaling pathways in visceral fat tissue compared to tenofovir disoproxil fumarate","authors":"Bryan Dulion , Arnold Z. Olali , Niyati Patel , Amber K. Virdi , Ankur Naqib , Jennillee Wallace , Ryan D. Ross","doi":"10.1016/j.antiviral.2025.106151","DOIUrl":"10.1016/j.antiviral.2025.106151","url":null,"abstract":"<div><div>Modern antiretroviral therapy (ART) is associated with rapid weight gain, which appears to be antiretroviral-specific. Tenofovir is a nucleoside reverse transcriptase inhibitor commonly employed as a backbone in many ART formulations. Tenofovir alafenamide (TAF) has been associated with significant weight gain in people living with HIV (PLWH) initiating ART. Interestingly, tenofovir disoproxil fumarate (TDF), has no impact on weight or may even be weight suppressive. The current study compared the impact of two tenofovir-based ART formulations on weight and adipose tissue. We utilized a humanized mouse model of HIV-infection and administered two clinically relevant ART combinations TAF/dolutegravir (DTG)/emtricitabine (FTC) and TDF/DTG/FTC. As expected, female mice treated with TAF/DTG/FTC had the greatest weight gain and fat accumulation, as measured by dual energy x-ray absorptiometry (DXA). As ART-induced accumulation of visceral adipose tissue is linked to mortality, we isolated visceral adipose tissue for targeted (qPCR) and non-targeted (RNAseq) gene expression. Mice treated with TAF/DTG/FTC had increased expression of adipocyte differentiation related genes, leptin and PPAR-γ. RNAseq revealed that while the expression patterns for both TAF/DTG/FTC and TDF/DTG/FTC treated mice were similar, there were key differences. Specifically, KEGG pathway analysis indicated that TAF/DTG/FTC treated mice showed suppression of multiple fatty acid metabolism related pathways, while TDF/DTG/FTC treated mice showed evidence for increased thermogenesis. The results suggest that weight gain associated with TAF-based ART may be due to impaired adipocyte mediated lipid handling, while suppressed weight gain with TDF-based ART may be secondary to increased browning of visceral adipocytes, although independent validation is necessary.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106151"},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of influenza A virus proliferation in mice via universal RNA interference 通过通用RNA干扰抑制甲型流感病毒在小鼠中的增殖。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-03-25 DOI: 10.1016/j.antiviral.2025.106149

Yu-Shen Kuo , Pei-Chuan Chiang , Chieh-Ying Kuo , Chung-Guei Huang , Ming-Ling Kuo , Ya-Fang Chiu

{"title":"Inhibition of influenza A virus proliferation in mice via universal RNA interference","authors":"Yu-Shen Kuo , Pei-Chuan Chiang , Chieh-Ying Kuo , Chung-Guei Huang , Ming-Ling Kuo , Ya-Fang Chiu","doi":"10.1016/j.antiviral.2025.106149","DOIUrl":"10.1016/j.antiviral.2025.106149","url":null,"abstract":"<div><div>Influenza A virus (IAV) is a respiratory pathogen that causes seasonal outbreaks and periodic pandemics. As frequent mutations in the IAV viral genome often render vaccines ineffective or inefficient in preventing the latest outbreak, there is a need to explore other preventive strategies to control the disease. This study sought to investigate the use of antiviral short hairpin RNA (shRNA), delivered by a recombinant adeno-associated virus (AAV), for the prevention of IAV infections. Conserved regions with less than 10 % of variation were identified from IAV genome sequences deposited in the National Center for Biotechnology Information (NCBI) database between 2000 and 2023. The shRNA targeting these conserved sequences was transcribed from the human RNA polymerase III U6 promoter in an AAV system. This study demonstrates that AAV delivery of shRNA against IAV genes encoding two of the viral RNA-dependent RNA polymerase subunits, PB1 and PB2, inhibits the replication of IAV H1N1 and H3N2 viruses in Madin-Darby canine kidney (MDCK) cells. Delivery of shPB1 to lung tissue in mice through AAV also provided effective protection against IAV infection. These results offer support for a shRNA-based strategy of influenza prevention.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"238 ","pages":"Article 106149"},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the host transcription factor HSF1 prevents human cytomegalovirus replication in vitro and in vivo 靶向宿主转录因子HSF1在体外和体内阻止人巨细胞病毒复制

IF 4.5 2区医学

Antiviral research Pub Date : 2025-03-25 DOI: 10.1016/j.antiviral.2025.106150

Dilruba Akter , Juthi Biswas , Shima Moradpour , Meghan F. Carter , Michael J. Miller , Dennis J. Thiele , Eain A. Murphy , Christine M. O'Connor , Jennifer F. Moffat , Gary C. Chan

{"title":"Targeting the host transcription factor HSF1 prevents human cytomegalovirus replication in vitro and in vivo","authors":"Dilruba Akter , Juthi Biswas , Shima Moradpour , Meghan F. Carter , Michael J. Miller , Dennis J. Thiele , Eain A. Murphy , Christine M. O'Connor , Jennifer F. Moffat , Gary C. Chan","doi":"10.1016/j.antiviral.2025.106150","DOIUrl":"10.1016/j.antiviral.2025.106150","url":null,"abstract":"<div><div>FDA-approved antivirals against HCMV have several limitations, including only targeting the later stages of the viral replication cycle, adverse side effects, and the emergence of drug-resistant strains. Antivirals targeting host factors specifically activated within infected cells and necessary for viral replication could address the current drawbacks of anti-HCMV standard-of-care drugs. In this study, we found HCMV infection stimulated the activation of the stress response transcription factor heat shock transcription factor 1 (HSF1). HCMV entry into fibroblasts rapidly increased HSF1 activity and subsequent relocalization from the cytoplasm to the nucleus, which was maintained throughout viral replication and in contrast to the transient burst of activity induced by canonical heat shock. Prophylactic pharmacological inhibition or genetic depletion of HSF1 prior to HCMV infection attenuated the expression of all classes of viral genes, including immediate early (IE) genes, and virus production, suggesting HSF1 promotes the earliest stages of the viral replication cycle. Therapeutic treatment with SISU-102, an HSF1 inhibitor tool compound, after IE expression also reduced the levels of L proteins and progeny production, suggesting HSF1 regulates multiple steps along the HCMV replication cycle. Leveraging a newly developed human skin xenograft transplant murine model, we found prophylactic treatment with SISU-102 significantly attenuated viral replication in transplanted human skin xenografts as well as viral dissemination to distal sites. These data demonstrate HCMV infection rapidly activates and relocalizes HSF1 to the nucleus to promote viral replication, which can be exploited as a host-directed antiviral strategy.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106150"},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

“Insights in the RSV L polymerase function and structure” “RSV L聚合酶功能和结构的见解”。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-03-22 DOI: 10.1016/j.antiviral.2025.106148

Brecht Bonneux , Martina Ceconi , Kim Stobbelaar , Florence Herschke , Peter Delputte

{"title":"“Insights in the RSV L polymerase function and structure”","authors":"Brecht Bonneux , Martina Ceconi , Kim Stobbelaar , Florence Herschke , Peter Delputte","doi":"10.1016/j.antiviral.2025.106148","DOIUrl":"10.1016/j.antiviral.2025.106148","url":null,"abstract":"<div><div>Respiratory syncytial virus (RSV) continues to have a large medical and economic impact worldwide, mainly in infants, elderly, and immunocompromised patients. While several vaccines and prophylactic antibodies are now available, effective treatment options are still needed. A highly interesting target for treatment is the replication process of the virus, in which the viral polymerase complex is critical. A critical protein of this complex is the RSV large (L) protein, which harbors multiple enzymatic functions that are all interesting targets for antiviral drug discovery. Unfortunately, not all structural parts of this L protein are currently resolved, which makes antiviral drug design and optimization challenging. In this review, an overview is given of current knowledge on the RSV L structure. Furthermore, a comparison is made between the L proteins of RSV and human metapneumovirus (hMPV), which, based on their sequence similarity, could shed light on missing structural gaps. New insights into the RSV and hMPV L protein structures are given, by modeling unresolved domains with AlphaFold2 and Alphafold3. While more structural studies are needed to confirm the modeling data, there is clearly potential for development of treatments targeting the L protein, for RSV and closely related viruses.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106148"},"PeriodicalIF":4.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

α-Glucosidase inhibitors as broad-spectrum antivirals: Current knowledge and future prospects α-葡萄糖苷酶抑制剂作为广谱抗病毒药物：目前的知识和未来的展望。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-03-20 DOI: 10.1016/j.antiviral.2025.106147

James WJ. Kang , Kitti Wing Ki Chan , Subhash G. Vasudevan , Jenny G. Low

引用次数: 0