Antiviral research最新文献

{"title":"A monoclonal antibody targeting conserved regions of pre-fusion protein cross-neutralizes Nipah and Hendra virus variants","authors":"Tao Li ,&nbsp;Hua Xu ,&nbsp;Mengyi Zhang ,&nbsp;Jianhui Nie ,&nbsp;Binfan Liao ,&nbsp;Jingshu Xie ,&nbsp;Yinan Jiang ,&nbsp;Yawen Liu ,&nbsp;Pingju Ge ,&nbsp;Chunhui Zhao ,&nbsp;Ziqi Sun ,&nbsp;Yunbo Bai ,&nbsp;Maoling Tang ,&nbsp;Xiaodong Su ,&nbsp;Youchun Wang ,&nbsp;Weijin Huang","doi":"10.1016/j.antiviral.2025.106215","DOIUrl":"10.1016/j.antiviral.2025.106215","url":null,"abstract":"<div><div>Nipah virus (NiV) and Hendra virus (HeV) have an extremely high case fatality, leading to hundreds of deaths in several countries around the globe. Belonging to the same genus Henipavirus (HNV), the two species have a high degree of sequence similarity, resulting in cross-neutralizing immunity under favorable conditions. Here, we obtained ten anti-NiV-F monoclonal antibodies using hybridoma technology, and verified that these antibodies had potent neutralizing activities against epidemic NiV strains from different regions using a pseudovirus assay, and the neutralizing concentration reached the nanogram per milliliter level. Moreover, two of the antibodies, NiF03-3C9 and NiF03-2F6, were found to have cross-neutralizing activity against HeV, which was even stronger than that against NiV. Epitope competition analysis revealed two classes of epitopes for these antibodies. Cryo-electron microscopy showed that NiF03-3C9 binds to lateral residues of the prefusion F protein trimer, highly conserved in both Nipah and Hendra. The protective potency of the antibodies was also validated using in vivo pseudovirus infection models of Nipah and Hendra viruses. The mAbs developed in this study and their conserved cross-neutralizing epitopes elucidated by structural analysis may contribute to the control of highly pathogenic HNV outbreaks.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"240 ","pages":"Article 106215"},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336025","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}

{"title":"RXR agonist S169 inhibits HBV/HDV entry in vitro by disrupting KIF4-dependent NTCP trafficking","authors":"Sameh A. Gad ,&nbsp;Doaa A. Abo Elwafa ,&nbsp;Saied A. Hussein ,&nbsp;Kento Fukano ,&nbsp;Takanobu Kato ,&nbsp;Ikuo Shoji ,&nbsp;Kazuaki Chayama ,&nbsp;Masamichi Muramatsu ,&nbsp;Masanori Isogawa ,&nbsp;Takaji Wakita ,&nbsp;Daniel Merk ,&nbsp;Hussein H. Aly","doi":"10.1016/j.antiviral.2025.106214","DOIUrl":"10.1016/j.antiviral.2025.106214","url":null,"abstract":"<div><div>Chronic hepatitis B (HBV) and hepatitis D (HDV) viral infections pose serious global health challenges, and the lack of curative therapies calls for the development of new antiviral approaches. Recently, we have identified the Kinesin Family Member 4 (KIF4) as a crucial regulator of the surface transport for NTCP (HBV/HDV entry receptor). Our research has shown that the pan-RXR agonist, Bexarotene, suppresses KIF4 expression and inhibits HBV/HDV infections. However, the clinical use of Bexarotene is limited by poor physicochemical and pharmacokinetic (PK) properties and significant side effects. Here we investigated chemically diverse RXR modulators with tuned activity, and identified the RXR agonist S169 as a novel HBV/HDV entry inhibitor. S169 effectively blocks HBV and HDV infections in primary human hepatocyte (PXB) cultures without evident cytotoxicity. S169's suppressive effect on HBV infection was confirmed by reduction of secreted HBsAg and HBeAg, as well as inhibition of HBV cccDNA, pregenomic RNA, and intracellular HBV DNA. Mechanistically, S169 suppressed FOXM1-mediated KIF4 expression, leading to decreased NTCP surface levels and a marked decrease in HBV preS1 peptide binding to the hepatocyte cell surface. S169 is reported to exhibit enhanced oral bioavailability, favorable PK parameters, lower toxicity compared to Bexarotene. Interestingly, S169 induced a modest inhibition of NTCP-mediated bile acid transport up to 10 μM, which remained unchanged at higher concentrations. Furthermore, S169 significantly impeded HBV spread in HBV infected long-time cultured PHHs (PXB). We speculate that S169 can be a promising seed for the development of novel oral HBV and HDV antiviral therapeutics.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"240 ","pages":"Article 106214"},"PeriodicalIF":4.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290745","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}

{"title":"Molecular mechanisms of hepatitis B virus entry inhibition by a bile acid derivative INT-767 binding to the preS1 region","authors":"Akinori Okumura ,&nbsp;Yukiko Muraki ,&nbsp;Jun Arai ,&nbsp;Sayaka Nishimura ,&nbsp;Noriko Inden ,&nbsp;Kazumasa Sakamoto ,&nbsp;Tomoya Kitada ,&nbsp;Satoshi Kimoto ,&nbsp;Rena Kitano ,&nbsp;Tadahisa Inoue ,&nbsp;Yukiko Yamashita ,&nbsp;Yusuke Iguchi ,&nbsp;Hirofumi Ohashi ,&nbsp;Koichi Watashi ,&nbsp;Takaji Wakita ,&nbsp;Mizuho Une ,&nbsp;Kiyoaki Ito","doi":"10.1016/j.antiviral.2025.106213","DOIUrl":"10.1016/j.antiviral.2025.106213","url":null,"abstract":"<div><div>Hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide, necessitating the development of novel antiviral agents targeting various steps in the HBV life cycle. The HBV preS1 region mediates critical steps in viral entry, including binding to sodium taurocholate co-transporting polypeptide (NTCP), making it a potential target for anti-HBV drug development. Our previous study suggested that the bile acid derivative INT-767 preferentially attaches to preS1 rather than to NTCP on hepatocytes, indicating that HBV infection is inhibited by INT-767 binding to an important domain of preS1. To elucidate the specific binding interactions between INT-767 and the preS1 region, we performed a preS1 binding assay using fluorescently labeled preS1 peptides and NTCP-expressing HepG2 cells to assess INT-767 binding efficacy. Furthermore, we evaluated the effect of amino acid substitutions in preS1 on both INT-767 binding and HBV infectivity in primary human hepatocytes. The preS1 binding assay revealed that INT-767 interacts specifically with Phe13, Phe14, and His17 in the NTCP-binding region of preS1. Functional analysis demonstrated that substitution of these residues with alanine significantly reduced HBV infectivity, indicating their crucial role in viral entry. INT-767 binding to these residues effectively blocked preS1 interaction with NTCP, thereby inhibiting HBV infection. These findings highlight a novel antiviral mechanism by which INT-767 exerts its anti-HBV effects through direct interaction with preS1, providing a potential therapeutic strategy targeting HBV entry.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"240 ","pages":"Article 106213"},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293258","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}

{"title":"A novel cellular tool for screening human pan-coronavirus antivirals","authors":"Ching-Wen Chang ,&nbsp;Neelam Oswal ,&nbsp;Madhuvika Murugan ,&nbsp;Kira Goldgirsh ,&nbsp;Wenshan Tsao ,&nbsp;Steven Park ,&nbsp;David S. Perlin","doi":"10.1016/j.antiviral.2025.106212","DOIUrl":"10.1016/j.antiviral.2025.106212","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a pressing global threat, having emerged in December 2019. Alongside it, Middle East respiratory syndrome coronavirus (MERS-CoV), a highly pathogenic human coronavirus, was identified in 2012 and continues to cause seasonal outbreaks in the Middle East. The persistence of these deadly human coronaviruses underscores the need for ongoing research on broad-spectrum antivirals. Human alveolar A549 cells have been widely used to study respiratory virus infections; however, there is a lack of standardized cell models that are permissive to these diverse lethal coronaviruses. To facilitate the assessment and validation of antiviral treatments, a robust human cell model that is susceptible to SARS-CoV-2, MERS-CoV, and other human coronavirus family members is indispensable. SARS-CoV-2 uses the angiotensin converting enzyme 2 (Ace2) receptor for entry and transmembrane serine protease 2 (Tmprss2) to prime its spike protein, while MERS-CoV relies on the dipeptidyl peptidase 4 receptor (Dpp4) for cellular entry, both of which are minimally expressed in A549 cells. In this study, we fine-tuned the expression levels of each receptor for optimal viral entry and infectivity using lentiviral transduction, cell sorting and clone selection. We successfully developed a robust human cell model expressing multiple viral receptors and demonstrated its susceptibility to both lethal coronaviruses and seasonal human coronaviruses, OC43 and 229E. We also compared two known 3C-like protease inhibitors and found that Nirmatrelvir is superior to Pomotrelvir in terms of pan-coronavirus antiviral activity. Furthermore, we tested 13 known antimalarial drugs and identified Halofantrine as having antiviral activity against SARS-CoV-2. Our findings suggest that this novel human cell model is a valuable and versatile tool for the screening and identification of pan-CoV antiviral drugs.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"240 ","pages":"Article 106212"},"PeriodicalIF":4.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282271","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}

{"title":"Marburg and Kasokero viruses elicit differential antiviral innate immune control by their natural reservoir bat, the Egyptian rousette (Rousettus aegyptiacus)","authors":"Shannon G.M. Kirejczyk ,&nbsp;Amy J. Schuh ,&nbsp;Brian R. Amman ,&nbsp;Jonathan C. Guito ,&nbsp;Tara K. Sealy ,&nbsp;James C. Graziano ,&nbsp;Jian Zhang ,&nbsp;Megan E.B. Jones ,&nbsp;Corrie C. Brown ,&nbsp;Jonathan S. Towner","doi":"10.1016/j.antiviral.2025.106211","DOIUrl":"10.1016/j.antiviral.2025.106211","url":null,"abstract":"<div><div>To investigate the antiviral innate immune responses of natural reservoir bats, we conducted a histopathological analysis of Egyptian rousettes (<em>Rousettus aegyptiacus</em>) experimentally infected with either of two divergent RNA viruses they naturally host, Marburg virus (MARV; family <em>Filoviridae</em>) and Kasokero virus (KASV; family <em>Nairoviridae</em>). Bats were serially euthanized at similar post-infection time points and tissue-based analyses focused on the liver, the primary target for both viruses. At 3 days post-infection (DPI), <em>in situ</em> hybridization (ISH) signal for replicating MARV was 300x less evident than that of KASV, with little immune cell recruitment and localized interferon (IFN)-stimulated responses suggesting a tendency towards superb virus replication control and non-cytolytic viral clearance. By comparison, an early burst of hepatocellular KASV replication correlated with robust, tissue-wide IFN-stimulated responses, mononuclear phagocyte apoptosis, targeted natural killer (NK) and/or natural killer T (NKT) cell responses and localized cytokine induction, demonstrating the capacity to swiftly establish an antiviral state. The distinctive lack of IFN stimulated gene 15 and MARV RNA hepatocellular co-localization in a single MARV-infected bat with overt hepatitis suggests a fine-tuned role for IFN antagonism in Egyptian rousettes, and hints at how MARV-IFN pathway interactions might influence the evolution, transmission and maintenance of orthomarburgviruses in nature, whereas KASV is less adaptable to this vertebrate host. This work augments our understanding of bat immunology and suggests certain co-evolutionary relationships between bats and viruses. These defenses may be more broadly applicable to other viruses circulating in Egyptian rousettes and likely to other bat-virus relationships.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"240 ","pages":"Article 106211"},"PeriodicalIF":4.5,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265170","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}

{"title":"Retrospective analysis of steatosis effect on antiviral response and hepatocellular carcinoma risk in chronic hepatitis C","authors":"Saptarshi Bhattacharyya ,&nbsp;Ming-Lung Yu ,&nbsp;Phumelele Yvonne Siphepho ,&nbsp;Jee-Fu Huang ,&nbsp;Chia-Yen Dai ,&nbsp;Wan-Long Chuang ,&nbsp;Shu-Chi Wang","doi":"10.1016/j.antiviral.2025.106203","DOIUrl":"10.1016/j.antiviral.2025.106203","url":null,"abstract":"<div><div>Hepatic steatosis is increasingly the leading cause of liver disease and suboptimal virologic response in chronic hepatitis C virus (CHC) infections worldwide. In Taiwan, the prevalence of cirrhosis and liver disease among CHC patients with steatosis has surged, influenced mainly by Westernized dietary habits. This retrospective study aimed to assess how varying degrees of hepatic steatosis impact the severity of liver fibrosis and hepatocellular carcinoma (HCC) risk in CHC patients undergoing pegylated interferon (Peg-IFN) and ribavirin (RBV) treatment. We analyzed their treatment outcomes, HCC development, and baseline steatosis severity using Brunt's classification after 24 weeks of Peg-IFN/RBV treatment and a 14-year observation (2010–2024). Of 1121 CHC patients, 518 (46 %) had baseline steatosis. Patients with severe steatosis (S2/S3) were older, predominantly diabetic, and had higher fibrosis levels and BMI. Our data revealed that fibrosis was a significant risk factor, especially in mild steatosis cases. Among the cohort, 20 % developed HCC, with its incidence increasing with the degree of steatosis. Steatosis was notably prevalent in mild fibrosis cases. In conclusion, in CHC patients treated with IFN therapy, the steatosis degree directly correlated with fibrosis severity and HCC development. Notably, baseline steatosis emerged as a risk factor in patients showcasing mild liver fibrosis.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"240 ","pages":"Article 106203"},"PeriodicalIF":4.5,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257271","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}

{"title":"High-throughput screening for identification of influenza a inhibitors using a cell-based immunofluorescence assay","authors":"Yohanka Martinez-Gzegozewska ,&nbsp;Lynn Rasmussen ,&nbsp;N. Miranda Nebane ,&nbsp;Sara McKellip ,&nbsp;Dee Radzieta ,&nbsp;Anna Manuvakhova ,&nbsp;Andrew J. Reece ,&nbsp;Pedro Ruiz ,&nbsp;Sixue Zhang ,&nbsp;Omar Moukha-Chafiq ,&nbsp;Melinda Sosa ,&nbsp;Corinne Augelli-Szafran ,&nbsp;Richard Whitley ,&nbsp;Robert Bostwick ,&nbsp;Paige Vinson","doi":"10.1016/j.antiviral.2025.106209","DOIUrl":"10.1016/j.antiviral.2025.106209","url":null,"abstract":"<div><div>A highly sensitive cell-based imaging assay has been used to screen a 200,000 compounds library for potential influenza antivirals. Compounds were screened at a concentration of 10 μM against the influenza strain A/Udorn/72 (H3N2) and the duplex capability of the assay was taken advantage of to select compounds with no or low cytotoxicity. The assay was also used for confirmation in concentration-response of the active compounds. In the set of confirmed hits, three major structural clusters, 23 minor clusters and 86 singletons were identified. Further evaluation of anti-influenza activity was performed for two additional influenza strains of the H1N1 subtype, A/WSN/33 and A/California/07/09. Three compounds from cluster A, SRI-44211, SRI-44215 and SRI-44221 showed selectivity indices for the pandemic strain A/California/07/09 in the range of 54.3–252, providing evidence that the core structure of cluster A could play a relevant role in their inhibitory potency and may serve as a starting point for future hit-to-lead optimization efforts.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"240 ","pages":"Article 106209"},"PeriodicalIF":4.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246100","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}

{"title":"Residual viral expression in siRNA-treated HBV-replicating cell and mouse models","authors":"Mingzhu Xu ,&nbsp;Yuyan Qian ,&nbsp;Ziyang Song ,&nbsp;Haiyu Wang ,&nbsp;Lei Yue ,&nbsp;Jiangxia Liu ,&nbsp;Yaming Li ,&nbsp;Wenjing Zai ,&nbsp;Zhenghong Yuan ,&nbsp;Jieliang Chen","doi":"10.1016/j.antiviral.2025.106210","DOIUrl":"10.1016/j.antiviral.2025.106210","url":null,"abstract":"<div><div>Small interfering RNA (siRNA) effectively reduces hepatitis B virus (HBV) antigens, but recent clinical trial results indicate that its efficacy and durability remain unsatisfied, warranting further mechanistic investigation. This study aims to explore the expression patterns and potential sources of residual viral nucleic acids following siRNA treatment in both <em>in vitro</em> and <em>in vivo</em> models, enhancing the understanding of siRNA's antiviral effects. Biochemical methods, combined with immunofluorescence and fluorescent <em>in situ</em> hybridization techniques, were employed to analyze the antiviral effects of siRNAs targeting the S, X, and C coding regions of HBV at the single-cell level in HBV-infected HepG2-NTCP cell model and rAAV8-HBV1.3 mouse model. The results indicate that, in both the <em>in vitro</em> and <em>in vivo</em> models, a single dose of siRNA treatment did not significantly reduce the proportion of cells positive for any HBV marker. Residual viral antigen and nucleic acid signals were broadly distributed across individual cells. The antiviral effects of siRNA generally exhibit dose-dependent inhibition of HBV, but vary across different viral markers, potentially due to factors such as target region, engagement, and the viral expression patterns within cells, with a potential inhibition plateau for core particle DNA. Furthermore, the combination of siRNA and the HBV core inhibitor GLS4 further reduced intracellular viral DNA in primary human hepatocytes. These findings obtained from experimental models incorporating <em>in situ</em> detection techniques reveal the expression patterns of residual HBV antigens and nucleic acids under siRNA treatment, deepening the understanding of its antiviral effects, while clinical complexities require further investigation.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"240 ","pages":"Article 106210"},"PeriodicalIF":4.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246101","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}

{"title":"Unveiling SARS-CoV-2's heart: role, structure and inhibition of SARS-CoV-2 RNA-dependent RNA polymerase","authors":"Paolo Malune,&nbsp;Francesca Esposito,&nbsp;Enzo Tramontano","doi":"10.1016/j.antiviral.2025.106208","DOIUrl":"10.1016/j.antiviral.2025.106208","url":null,"abstract":"<div><div>SARS-CoV-2 emergence in late 2019 represented an incredible challenge for virological research and the development of novel as well as repurposed antiviral agents. Among the targeted viral proteins, one is nsp12 that carries the RNA-dependent RNA polymerase (RdRp) activity, essential for the viral replication. Together with nsp7 and nsp8 cofactors, having an essential role in aiding processivity and associated with several other nonstructural proteins such as helicase, methyltransferase, endo- and exonuclease, nsp12 forms the large viral replication and transcription complex (RTC). Within such RTC, nsp12 catalyzes the synthesis of one of the longest RNA genomes in the viral world, requiring exceptional speed, processivity and fidelity compared to other viral RdRps. Moreover, the peculiar replication cycle of coronaviruses requires nsp12 to perform less conventional functions in backtracking on the viral genome for proof-reading activity and “jumping” during discontinuous synthesis of subgenomic mRNAs. The structure of the minimal RTC was resolved with a resolution &lt;3 Å by cryo-electron microscopy in complex with RNA and with inhibitors, opening the doors to structural studies on its functions and drug development. Given its essential role in viral replication, extensive research was carried out over the last years to identify both nucleoside (NI) and non-nucleoside (NNI) inhibitors, resulting in two NIs reaching clinical use, although their efficacy <em>in vivo</em> is still under evaluation. This review aims at summarizing the currently known structural and functional aspects and the state-of-the art in drug discovery for SARS-CoV-2 RdRp.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"240 ","pages":"Article 106208"},"PeriodicalIF":4.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231656","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}

{"title":"Tirofiban protects mice against severe RSV pneumonia by potentially inhibiting platelet activation via the GPIbα–vWF pathway","authors":"Yu-Si Luo ,&nbsp;Huyan Shen ,&nbsp;Ping Ling ,&nbsp;Han Gao ,&nbsp;Hong Peng ,&nbsp;Haiyan Zhou ,&nbsp;You Dai ,&nbsp;Pingping Zhang ,&nbsp;Fang Chen ,&nbsp;Siyu Lin ,&nbsp;Jin-Fu Li ,&nbsp;Yan-Fei Qi ,&nbsp;Zhongshan Cheng ,&nbsp;Gang Liu ,&nbsp;Ke Zhang","doi":"10.1016/j.antiviral.2025.106207","DOIUrl":"10.1016/j.antiviral.2025.106207","url":null,"abstract":"<div><div>This study aimed to investigate the role of platelets in mediating lethal respiratory syncytial virus (RSV) infection and to explore the potential of antiplatelet therapy as a novel therapeutic approach for RSV infection. <em>Ex vivo</em> and <em>in vivo</em> experiments were used to study the effects of lethal RSV infection on platelet activation, aggregation, and thrombus formation. The emerging therapeutic effect of tirofiban, a GPIIb/IIIa inhibitor, in mitigating RSV-induced pneumonia was also evaluated. Mice infected with a highly virulent RSV strain (R96-5) developed severe RSV pneumonia and showed significantly increased mortality rates, along with extensive platelet infiltration and thrombus formation in the lungs. In situ hybridization revealed co-localization of RSV nucleocapsid RNA with the platelet GPIbα gene in lung tissue. RSV infection induced marked platelet aggregation through the GPIbα-vWF pathway. Notably, tirofiban significantly protected mice from severe pneumonia caused by R96-5. These findings highlight the critical involvement of platelet activation and aggregation in RSV infection and suggest that targeting platelet through the GPIbα–vWF signaling axis may represent a promising therapeutic strategy for severe RSV infection.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"240 ","pages":"Article 106207"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212136","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}