LIFE SCIENCES
·
2024
·
IF 5.2
Fang Chen,Huyan Shen,Gang Liu,Pingping Zhang,Lin Zhang,Siyu Lin,Han Gao,Hong Peng,Yan-Fei Qi,Yan Chen,Yinhui Jiang,Jiandong Huang,Xiangchun Shen,Yu-Si Luo,Ke Zhang
Aims The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism. Materials and methods RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca 2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil. Key findings Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca 2+ channels and inhibiting virus replication. Significance Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.
研究领域:
药理学
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病毒学
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免疫学
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分子生物学
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JOURNAL OF VIROLOGY
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2024
·
IF 4
Yingcai Xiong,Keyu Tao,Tao Li,Yinghui Zhou,Zhaowei Zhang,Weiying Ou,Zhao Wang,Shouchuan Wang,Yayi Hou,Peng Cao,Jianjian Ji
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, with no currently available small-molecule drugs that are both safe and effective. A major obstacle in antiviral drug development is the rapid emergence of drug-resistant viral strains. Targeting multiple viral compounds may help mitigate the development of resistance. Herein, we conducted a drug screening using the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to identify compounds that simultaneously target the RSV fusion (F) protein, glycoprotein (G), and the host heparan sulfate proteoglycans (HSPGs). From this screening, 10 candidate compounds were identified for their ability to interact with all three targets. Among these 10 candidates, chebulagic acid (CHLA) and punicalagin (PUG) demonstrated the most potent inhibition of RSV replication. In vitro dose–response assays confirmed the antiviral efficacy of CHLA (IC50: 0.07864 µM) and PUG (IC50: 0.08065 µM). Further experiments revealed both CHLA and PUG disrupt RSV attachment and membrane fusion by targeting the RSV-F and G proteins, rather than HSPG. Notably, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with docking assays predicting their binding sites at cysteines 176 and 182. Additionally, CHLA enhanced the conformational stability of the RSV-F protein before fusion. In an in vivo study, both CHLA and PUG were shown to alleviate RSV-induced pulmonary pathology by reducing viral titers, mitigating lung injury, and suppressing the inflammatory responses in the lungs. Our findings suggest that CHLA and PUG hold potential as therapeutic agents for RSV infection.
研究领域:
病毒学
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药理学
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分子生物学
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中医药
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EMBO Molecular Medicine
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2026
·
IF 7.9
Liu Lijie,Yan Mengrong,Liang Ruoxu,Wu Qingxin,Qu Changbin,Wu Huiqi,Liao Zhi,Chen Huiyu,Zou Jingjing,Sun Zeyun,Niu Dongyu,Wu Liyuan,Zhao Li,Dai Jialing,Shen Jialun,Zhang Long,Zhang Wei,Peng Wei
Respiratory syncytial virus (RSV) remains a major cause of severe respiratory disease, and stabilization of the prefusion (preF) conformation of the F glycoprotein is central for vaccine development. Here, we report a structure-guided engineering strategy that enhances preF stability by reducing the hydrophobic cavity within the trimeric F protein. Targeted modifications at metastability-associated sites generated RVF-88, a disulfide-free stabilized preF immunogen that preserves key neutralizing epitopes, including antigenic site Ø, while exhibiting improved structural integrity and long-term storage stability. Formulated as an unadjuvanted bivalent vaccine, RVF-88 elicited potent neutralizing antibody responses and durable immune protection lasting up to 5 months in mice. Vaccination also protected both mice and cotton rats against RSV challenge. Structural analyses confirmed the intended cavity-reduction design, revealing a reduced apical hydrophobic cavity volume and surface area while maintaining the prefusion architecture. Together, these findings establish hydrophobic cavity reduction as a rational strategy for stabilizing prefusion RSV F and provide a promising next-generation vaccine candidate with improved stability and immunogenicity for further clinical development.
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EMBO Molecular Medicine
·
2026
·Vol. 18
·期 5
·1866
·
IF 7.9
Qianqian Wang,Xianliang Ke,Entao Li,Dongxiang Hong,Zekai Cheng,Hongxin Li,Jiachen Zhang,Tengchuan Jin,Rui Gong,Bo Shu,Sandra Chiu
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in infants and elderly individuals. Although nirsevimab represents a recent breakthrough against RSV infection, the emergence of resistant variants highlight the need for additional antiviral strategies. Here, we report two nanobodies (Nbs), 1G9 and 1D8, that target the RSV fusion (F) protein and exhibit high neutralizing activity against RSV subtypes. In vivo, the Nbs-Fc demonstrated robust prophylactic and therapeutic efficacy. Cryo-electron microscopy revealed that 1G9 and 1D8 specifically engage a conformational pivot site within antigenic site IV, crosslinking the metastable heptad repeats B (HRB) and the conformationally stable domain II of the F protein. This interaction stabilizes the prefusion conformation and prevents the structural rearrangement required for membrane fusion. Notably, the binding residues are highly conserved across RSV subtypes, accounting for the broad-spectrum neutralization observed. Together, our findings identify a structurally conserved and functionally critical epitope on RSV F and highlight 1G9 and 1D8 as promising candidates for next-generation prophylactic and therapeutic interventions against RSV. Respiratory syncytial virus (RSV) poses a significant threat to the health of infants and the elderly. Although the current use of nirsevimab for prevention represents a major breakthrough, its efficacy remains limited. There is an imperative need to develop a safe, broad-spectrum, and cost-effective next-generation RSV neutralizing antibodies (Nbs). Respiratory syncytial virus (RSV) poses a significant threat to the health of infants and the elderly. Although the current use of nirsevimab for prevention represents a major breakthrough, its efficacy remains limited. There is an imperative need to develop a safe, broad-spectrum, and cost-effective next-generation RSV neutralizing antibodies (Nbs).
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FASEB JOURNAL
·
2026
·Vol. 40
·期 13
·e72080
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IF 4.3
Pingping Zhang,Meihua Luo,Siyu Lin,Shaoju Hu,Ping Ling,Guikang Wang,You Dai,Xiaolu Cui,Yu-Si Luo,Ke Zhang
Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections globally, with particularly severe implications for infants and the elderly population. Despite the substantial burden on public health, effective therapeutic options for the treatment of RSV infections remain limited. The pathogenesis of RSV is characterized by complex inflammatory responses, while high-mobility group box 1 (HMGB1), a damage-associated molecular pattern protein, is known to play a role in amplifying inflammation. However, the specific role of HMGB1 in RSV infection has not been thoroughly investigated. This study aims to elucidate the role of HMGB1 in RSV replication and to evaluate its potential as a target for antiviral therapy. The interaction between the RSV nucleocapsid (N) protein and HMGB1 was demonstrated through co-immunoprecipitation and mass spectrometry. Knockdown or overexpression of HMGB1 by small interfering RNA or pCMV-HA-HMGB1 resulted in a significant reduction or induction in RSV replication in vitro, thereby confirming the critical role of HMGB1 in viral propagation. Moreover, structure-based molecular docking analyses identified glycyrrhizic acid (GA) and amlexanox (AMX) as high-affinity ligands for HMGB1. In cellular studies, both GA and AMX effectively inhibited RSV replication in a dose-dependent manner while selectively suppressing HMGB1's secretion to the cytoplasm or extracellular space from RSV-infected cells. AMX was found to down-regulate HMGB1 expression while GA did not. In experiments using lethal murine RSV infection models, treatment with GA and AMX significantly improved survival rates and reduced lung pathology. In conclusion, these findings suggest that HMGB1 is a promising therapeutic target for RSV infection and highlight GA and AMX as potential antiviral candidates that can modulate HMGB1-mediated immunopathology. Graphical Direct binding between RSV N protein and HMGB1 is validated via IP-MS. Silencing or overexpression of HMGB1 potently restricted or elicited viral replication. Molecular docking identified GA and AMX as HMGB1-interacting candidates with prominent in vitro and in vivo anti-RSV efficacy. Mechanistically, GA preserves nuclear HMGB1 to block its secretion, while AMX reduces total HMGB1 abundance; both approaches limit cytoplasmic and extracellular HMGB1 release, suppressing RSV replication and downstream inflammation.
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BIOMEDICINE & PHARMACOTHERAPY
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2021
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IF 6.53
Yi-yu Liang,Kun-wei Li,Feng-jv Niu,Ying Li,Hao-cheng Wei,Yun-lei Dai,Yun-yu Wang,Chang-zheng Zhou,Xin-huan Wan
Objective To investigate the antiviral effect of Salvia plebeia R. Br. polysaccharides (SPP) against RSV and underlying mechanisms. Methods SPP was extracted via alcohol-precipitation method and extract was separated into various fractions using ultrafiltration method. The polysaccharide content was determined using UV-Vis. Antiviral effect of SPP and fractions was measured using MTT method and Reed-Muench method. Sixty Balb/c mice were randomly divided into 6 groups, and received either Ribavirin or SPP. Their body weight and food intake were recorded every day throughout the experiment period. The lung index inhibition ratio and pulmonary virus titer were determined followed by the histological analysis of lungs. Furthermore, time-of-addition and effective stage analysis were carried out to determine the mechanism of action. The TLR-3 and TLR-4 levels in the lungs were determined using qRT-PCR. The levels of IFN-γ, IL-2 and TNF-α in serum were determined using ELISA. Results The SPP content is 4.396%. SPP has shown a good anti-RSV effect both in vitro (TI = 123.041) and in vivo models. The antiviral activity of fractions with molecular weight ≥ 10,000 is found to possess more potent antiviral activity than other fractions. SPP inhibits the RSV proliferation and reduces the lung lesions induced by RSV. The mechanism of action involves the inhibition of TLR-3 and TLR-4 in lungs, up-regulation of IFN-γ and IL-2, and down-regulation of TNF-α in serum. It is also shown to improve the body’s immune function. Conclusion SPP has a potential to treat diseases caused by RSV.
研究领域:
药理学
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免疫学
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病毒学
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Journal of Advanced Research
·
2026
·
IF 17.1
Jiaxin Su,Lingcheng Wu,Huiru Zhu,Haoru Wang,Xiaoya He,Bing Liang,Jinhua Cai
Introduction Acute kidney injury (AKI) is a devastating global health burden. Its pathogenesis, particularly in ischemia/reperfusion (I/R) injury, centers on a vicious cycle between a reactive oxygen species (ROS)-driven inflammatory storm and severe mitochondrial dysfunction in renal tubular cells. While activation of the SIRT1/PGC-1α pathway is a promising therapeutic target for mitochondrial recovery, its potent agonist resveratrol (Rsv) suffers from poor bioavailability, and monotherapy fails to address the concomitant inflammatory pathology. Objective This study aimed to develop a kidney-targeted theranostic nanoplatform that synergistically breaks this pathological cycle. We hypothesized that a nanoplatform co-delivering Rsv and a ROS-scavenging component could concurrently suppress inflammation via direct ROS elimination and restore mitochondrial homeostasis via SIRT1/PGC-1α activation, with integrated magnetic resonance imaging (MRI) capability for monitoring. Methods We engineered a theranostic nanoplatform designated Rsv@HMnO 2 -HA (HMRH NPs). The platform was constructed by loading Rsv into hollow mesoporous manganese dioxide (HMnO 2 ) nanozymes, followed by surface coating with hyaluronic acid (HA) for active targeting to CD44 receptors over expressed on injured renal tubules. The system’s physicochemical properties were thoroughly characterized. Its therapeutic efficacy and theranostic performance were systematically evaluated in a well-established murine model of renal I/R-induced AKI, using a combination of biochemical assays, histological analysis, molecular biology techniques, and in vivo MRI. Results HMRH NPs successfully accumulated in injured kidneys and disassembled in situ. The HMnO 2 shell effectively scavenged excess ROS, attenuating the inflammatory response. The co-released Rsv activated the SIRT1/PGC-1α pathway, restored mitochondrial biogenesis, and improved cellular energy homeostasis. The released Mn 2+ ions enabled clear T 1 -weighted MRI contrast, allowing real-time visualization of renal targeting and therapeutic progression. Conclusion The results conclusively demonstrate that the HMRH NPs successfully implements a synergistic two-pronged therapeutic strategy. By co-delivering a ROS-scavenger and a mitochondrial-regenerative agent directly to the site of injury, the platform effectively disrupts the critical pathological crosstalk between inflammation and mitochondrial damage in AKI. This work presents a holistic, targeted, and image-guided nanomedicine strategy, offering a promising approach for the effective treatment and monitoring of AKI.
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NEW JOURNAL OF CHEMISTRY
·
2014
·Vol. 38
·期 7
·2935-2940
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IF 3.159
Lei Zhan,Wen Bi Wu,Xiao Xi Yang,Cheng Zhi Huang
Respiratory syncytial virus (RSV) mediates severe respiratory illness in infants and young children worldwide, and it is also a significant pathogen of the elderly and immune compromised. Due to the low infectious dose and high infectious rate of RSV, remarkably rapid and sensitive RSV detection is important for infection control and discovery of antiviral drugs. In this work, we described a highly sensitive enzyme-linked immunosorbent assay (ELISA) utilizing gold nanoparticles (AuNPs) for the detection of RSV. Gold nanoparticles were used as carriers of the signalling antibody anti-RSV–HRP (horseradish peroxidase) in order to achieve an amplification of the signal. Compared to conventional ELISA procedures, this assay resulted in higher sensitivity and shorter assay time in the range between 0.5 and 50 pg mL−1. The application of AuNPs to the enhanced ELISA showed acceptable reproducibility, stability, and could be readily applied to determination of other pathogens in clinical diagnostics.
研究领域:
病毒学
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纳米技术
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临床诊断
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免疫学
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Pharmaceuticals
·
2026
·Vol. 19
·期 4
·640
·
IF 5.7
Zeting Tan,Rongshun Liang,Adam Junka,Haoxuan Sun,Jie Jiang,Haojia Ma,Shisong Fang,Yanfang Sun
Background: Respiratory syncytial virus (RSV) is a leading global pathogen of acute lower respiratory tract infection, posing significant risks to infants, the elderly, and immunocompromised patients.Artemisia argyiLevl.et Vant Extract (AALE) and its active components have a variety of pharmacological effects, but their anti-RSV potential remains unclear. The aim of this study is to investigate the anti-RSV activity of AALE and parthenolide and its underlying mechanisms.Methods: Cell counting kit-8 (CCK-8) assay was used to determine the anti-RSV activities of AALE and parthenolide. Time-of-addition assay and phase of action analysis were used to explore the effect of drugs on the viral replication cycle. Quantitative polymerase chain reaction (qRCR), immunofluorescence (IF) and Western blot (WB) were used to investigate the effects of AALE and parthenolide on RSV-F gene and protein and on RIG-I/TLR-3 pathway related molecules in vitro. In vivo antiviral efficacy was verified by hematoxylin–eosin (HE) staining for lung histopathology, quantitative real-time PCR (qPCR) quantification of RSV-F, RIG-I, TLR-3, IRF3, IL-6, and IFN-β gene expression in lung tissues, and enzyme-linked immunosorbent assay (ELISA) for serum IL-6 and IFN-β levels.Results: AALE exhibited the strongest anti-RSV activity among the extracts (SI = 27.6), while parthenolide was the most potent monomeric compound (SI = 8.19). In vitro, both AALE and parthenolide were effective in the co-treatment and post-treatment models, reducing RSV-F gene and F protein levels in infected cells. Furthermore, they alleviated RSV infection by regulating RIG-I and TLR-3 pathway-related genes and proteins. In vivo, AALE and parthenolide suppressed lung index and RSV proliferation, attenuated lung injury, and down-regulated RIG-I, TLR-3, IRF3, IL-6, and IFN-β expression in the lungs of RSV-infected mice.Conclusions: AALE and its component parthenolide can inhibit the invasion and replication of RSV, making it a potential candidate for the treatment of RSV-related diseases.
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Frontiers in Immunology
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2022
·
IF 8.786
Qin Sheng,Huang Xianzhang,Qu Shaogang
Respiratory syncytial virus (RSV) infection is the most frequent cause of hospitalization in pediatric patients. Current systemic treatment and vaccines are not curative and re-infection is often associated with a more drastic incidence of the disease. Baicalin is a flavonoid isolated from Scutellaria baicalensis with potent anti-viral characteristics, namely against RSV. However, its precise mechanism of action remains unclear. Here, using in vitro methods and an in vivo murine model of RSV infection, we showed that baicalin inhibits RSV replication induces translational upregulation of type I interferons (IFNs), IFN-α and IFN-β, and reverses epithelial thickening in lung tissues. Moreover, baicalin inhibits transcription of the RSV non-structural proteins NS1 and NS2. Molecular docking and surface plasmon resonance-based affinity analysis showed that baicalin also binds to the α3 helix of the NS1 protein with an affinity constant of 1.119 × 10−5 M. Polysome profiling showed that baicalin inhibits translation of the RSV matrix protein (M) RNA. Baicalin mediates increased release of the ribosomal protein L13a from the large ribosomal subunit, where the extra ribosomal subunit L13a inhibits M RNA translation. These results comprehensively establish the multiple mechanisms by which baicalin induces a potent innate immune response against RSV infection.
研究领域:
病毒学
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免疫学
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药理学
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ACS Sensors
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2025
·
IF 9.1
Rujing Sun,Xin Li,Min Jiang,Yelongzi Cao,Yaqian Yang,Hao Wen,Zhenghan Shi,Chaobo Dai,Hao Liang,Qingjun Liu
Seasonal outbreaks of respiratory infections place a significant burden on hospital-centered diagnostic and treatment systems. Co-infections involving both bacterial and viral pathogens further complicate infection assessment, highlighting the need for rapid and accurate diagnostic tools. In this work, we present a ready-to-use, portable resonant sensing system capable of rapidly and quantitatively detecting key coinfection biomarkers in saliva, specifically C-reactive protein (CRP) and respiratory syncytial virus (RSV) fusion protein. The sensor operates via competitive immune binding within a hydrogel-based resonant structure, where biomarker binding induces shifts in resonant frequency that are wirelessly detected. To preserve antibody activity and hydrogel mechanical integrity, we developed an integrated, ready-to-use sensor system optimized for ultrasensitive detection. This platform enables analysis of unprocessed saliva samples within 5 min, achieving low limits of detection of 24 fg/mL for CRP and 31 fg/mL for RSV fusion protein. Quantitative analysis of patient samples demonstrated strong concordance with both enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) results. This portable sensing platform offers a promising solution for point-of-care coinfection diagnostics, supporting real-time infection monitoring and potentially easing the burden on healthcare systems.
研究领域:
生物医学工程
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传染病诊断
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生物传感器
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微流控技术
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免疫学
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即时检测
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Food & Function
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2024
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IF 5.1
Jianjian Ji,Yingcai Xiong,Keyu Tao,Tao Li,Weiying Ou,Yinghui Zhou,Wenyang Zhang,Ruogu Qi,Shouchuan Wang
Resveratrol, renowned for its antiviral properties, exhibits significant potential in combatting severe respiratory infections, particularly the respiratory syncytial virus (RSV). Nevertheless, the specific mechanism underlying its inhibition of RSV replication remains unexplored. Heparan sulfate proteoglycans (HSPGs) play a pivotal role as attachment factors for numerous viruses, offering a promising avenue for countering viral infections. Our research has unveiled that resveratrol effectively curbs RSV infection in a dose-dependent manner. Remarkably, resveratrol disrupts the initial stages of RSV infection by engaging with HSPGs, rather than interacting with RSV surface proteins like fusion (F) protein and glycoprotein (G). Resveratrol's affinity appears to be predominantly directed towards the negatively charged sites on HSPGs, thus impeding the binding of viral receptors. In an in vivo study involving RSV-infected mice, resveratrol demonstrates its potential by ameliorating pulmonary pathology. This improvement is attributed to the inhibition of pro-inflammatory cytokine expression and a reduction in viral load within the lungs. Notably, resveratrol specifically alleviates inflammation characterized by an abundance of neutrophils in RSV-infected mice. In summation, our data firstly illuminates how resveratrol combats RSV infection through interactions with HSPGs, positioning it as a promising candidate for innovative drug development targeting RSV infections. Our study provides insight into the mechanism of resveratrol antiviral infection.
研究领域:
病毒学
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药理学
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免疫学
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分子生物学
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