预约演示

更新于：2025-01-23

RSV F protein

更新于：2025-01-23

基本信息

别名

F、F1、F2

+ [8]

简介

Class I viral fusion protein (PubMed:23618766). Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state (PubMed:23618766). During viral and plasma cell membrane fusion, the coiled coil regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain (PubMed:23618766, PubMed:19966279). The formation of this structure appears to drive apposition and subsequent fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm (PubMed:23593008, PubMed:23618766). This fusion is pH independent and occurs at the plasma or endosomal membrane (Probable). The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate (PubMed:10864656). F protein is involved in the entry into the host cell through the interaction with host IGFR1 (PubMed:32494007). This interaction activates PRKCZ/PKCzeta that recruits host NCL/nucleolin to the apical cell surface where it can bind fusion glycoprotein F1 (PubMed:32494007, PubMed:21841784). Later in infection, F protein expressed at the plasma membrane of infected cells can mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis (PubMed:10438814). F protein may trigger p53-dependent apoptosis (PubMed:18216092). Major determinant of the species specificity of RSV infection (PubMed:12663767). The trimer of F1-F2 (F protein) also facilitates the attachment to host cell by binding to host heparan sulfate (PubMed:10864656). F protein is involved in the entry into the host cell through the interaction with host IGFR1 (PubMed:32494007). This interaction activates PRKCZ/PKCzeta that recruits host NCL/nucleolin to the apical cell surface where it can bind fusion glycoprotein F1 (PubMed:32494007). Later in infection, F protein expressed at the plasma membrane of infected cells can mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis (PubMed:10438814). F protein seems to trigger p53-dependent apoptosis (PubMed:18216092). Inactive precursor that is cleaved at two sites by a furin-like protease to give rise to the mature F1 and F2 fusion glycoproteins.

关联

项与 RSV F protein 相关的药物

Respiratory Syncytial Virus Vaccine(Moderna)

靶点

RSV F protein

作用机制

Respiratory syncytial virus F protein调节剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2024-08-22

RSVpreF

呼吸道合胞病毒疫苗（辉瑞大药厂）

靶点

RSV F protein

作用机制

Respiratory syncytial virus F protein调节剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

加拿大

首次获批日期2023-01-04

Nirsevimab

尼塞韦单抗

靶点

RSV F protein

作用机制

呼吸道合胞病毒F蛋白抑制剂

在研机构

AstraZeneca PLC [+7]

原研机构

AstraZeneca AB

在研适应症

呼吸道合胞体病毒感染 [+3]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2022-10-31

208

项与 RSV F protein 相关的临床试验

NCT06546800

/ Not yet recruitingN/A

SPECIAL INVESTIGATION FOR ABRYSVO INTRAMUSCULAR INJECTION -INVESTIGATION IN INDIVIDUALS AGED 60 YEARS OR OLDER-

This post-marketing study is a multicenter cohort study in individuals aged 60 years or older vaccinated with Abrysvo (RSV vaccine）designed to confirm the safety in individuals aged 60 years or older under actual clinical practice in Japan.

开始日期2024-12-27

申办/合作机构

Pfizer Inc.

NCT06710925

/ Not yet recruiting临床3期

A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Monoclonal Antibody TNM001 Injection Against Respiratory Syncytial Virus in High-risk Infants

This study is a Phase 3 randomized, double-blind, placebo-controlled study to evaluate the safety, efficacy, and immunogenicity of TNM001 in high-risk infants when entering their RSV season. Approximately 201 infants will be randomized in a ratio of 2:1 to receive TNM001 or placebo. All subjects will be followed for 270 days after dosing. This study will be conducted at approximately 20 sites in China.

开始日期2024-11-30

申办/合作机构

珠海泰诺麦博生物技术有限公司

NCT06684743

/ Recruiting临床4期IIT

A Pragmatic Randomized Trial to Evaluate the Vaccine Effectiveness of Abrysvo® for Preventing RSV Hospitalizations in Adults Aged 60 Years or Above

The purpose of this pragmatic randomized trial is to evaluate the vaccine effectiveness of bivalent RSV prefusion F vaccine (RSV vaccine) in older adults. Participants will be randomized 1:1 to either RSV vaccine or no RSV vaccine.

开始日期2024-11-18

申办/合作机构

Herlev and Gentofte Hospital

[+1]

100 项与 RSV F protein 相关的临床结果

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100 项与 RSV F protein 相关的转化医学

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0 项与 RSV F protein 相关的专利（医药）

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4,308

项与 RSV F protein 相关的文献（医药）

2025-05-01·Talanta

Smartphone-based mobile digital pressure sensor for quantitative point-of-care testing of respiratory syncytial virus infection

Article

作者: Zhang, Enhui ; Xiao, Ke ; Wang, Qi ; Xi, Yun ; Deng, Shikai ; Li, Jinfeng ; Li, Chengyao ; Zhang, Ling ; Li, Chengcheng ; Xu, Yanwen ; Lu, Jinhui ; Li, Tingting

Respiratory syncytial virus (RSV) is a major cause of acute respiratory tract infections in infants and elderly individuals, leading to hospitalisation and potentially fatal outcomes, posing a serious threat to global health and economy. This study proposes a smartphone-based mobile digital pressure sensor (smartphone-MDPS) for the quantitative detection of the RSV fusion protein (RSV-F) in clinical nasopharyngeal samples. The smartphone-MDPS utilized two monoclonal antibodies (mAbs) specific to the F protein, of which mAb1 was conjugated with Au@PtNPs (Au@PtNPs-mAb1) as the detection antibody and mAb2 was coupled with magnetic beads (MB-mAb2) as a coating antibody to establish a novel sandwich immunoassay. During the immune reaction, the substrate H₂O₂ was catalyzed to release O₂ gas by the Au@PtNPs nanozyme within the Au@PtNPs-mAb1-RSV-F-mAb2-MB immunocomplexes. The pressure intensity of O₂ was measured using a mobile digital pressure sensor and transmitted wirelessly to a smartphone application for analysis. The programming codes for the sensor module and Android app were developed considering the performance requirements of the smartphone-MDPS. With a quantitation range of 0.09-1.953 ng/mL, the system had a limit of quantitation (LOQ) of 0.09 ng/mL and a limit of detection (LOD) of 0.03 ng/mL. When nasopharyngeal samples from 27 patients with RSV infection and 46 healthy individuals were tested, the smartphone-MDPS and enzyme-linked immunosorbent assays (ELISA) exhibited 100 % positivity and specificity as well as a strong correlation coefficient (R² = 0.991) for quantitative measurements between these two assays. In conclusion, the smartphone-MDPS has high portability, affordability, efficiency, sensitivity, and specificity, making it a promising immunoassay for quantitative point-of-care testing of RSV infection.

2025-04-01·Biochimica et Biophysica Acta (BBA) - Bioenergetics

ADP-inhibited structure of non-catalytic site-depleted FoF1-ATPase from thermophilic Bacillus sp. PS-3

Article

作者: Nakano, Astuki ; Mitsuoka, Kaoru ; Kobayashi, Ren ; Yokoyama, Ken

The F₁ domain of F_oF₁-ATP synthases/ATPases (F_oF₁) possesses three catalytic sites on the three αβ interfaces, termed α_Eβ_E, α_Dβ_D, and α_Tβ_T, located mainly on the β subunits. The enzyme also has three non-catalytic ATP-binding sites on the three αβ interfaces, located mainly on the α subunits. When ATP does not bind to the non-catalytic site, F_oF₁ becomes significantly prone to ADP inhibition, ultimately resulting in the loss of ATPase activity. However, the underlying mechanism of ADP inhibition remains unclear. Here, we report the cryo-EM structure of the non-catalytic site-depleted (ΔNC) F_oF₁ from thermophilic Bacillus sp. PS-3, which completely lacks the ability to bind ATP (and ADP) upon transitioning to the ADP-inhibited form. The structure closely resembled the 81° rotated structure of the wild-type F_oF₁, except for minor movements in the C-terminal region of the α subunit. In this structure, unlike the wild-type enzyme, the catalytic site at α_Dβ_D, responsible for ATP hydrolysis, was occupied by ADP-Mg, with the absence of Pi. Furthermore, the catalytic site at α_Eβ_E, where ATP enters the F₁ domain during steady-state catalysis, is occupied by ADP, seemingly impeding further ATP binding to the enzyme. The structure suggests that the ADP-inhibited form of the F₁ domain is more likely due to differences in the nucleotide-binding states at the catalytic sites rather than structural differences.

2025-03-01·Molecular Therapy: Oncology

Cell-derived Newcastle disease virus variant with two amino acid substitutions near cleavage site of F shows favorable traits as oncolytic virus

Article

作者: van den Hoogen, Bernadette G ; Fouchier, Ron A M ; Groeneveld, Daphne ; de Graaf, J Fréderique ; van Nieuwkoop, Stefan ; Huberts, Marco

Newcastle disease virus (NDV) has shown encouraging effectiveness in in vitro, in vivo, and in early clinical trials as a viro-immunotherapy for pancreatic cancer. Previously, NDV used in clinical trials was produced in embryonated chicken eggs; however, egg-produced viruses are known to be partly neutralized by the human complement system when administered intravenously. Here, an NDV variant (NDV F0) was generated for production in mammalian cells, without passage in eggs. This was achieved by introducing the V-₁₀₆-M and L-₁₁₇-S amino acid substitutions upstream of the cleavage site in the F protein, resulting in rNDV F0-M, rNDV F0-S, and NDV F0-M/S. These viruses can be considered non-virulent as determined with in vivo pathogenicity testing and were neutralized less by the human complement system, which is explained by CD46 expression on the viral membrane. The inoculation of 10 pancreatic cancer cell lines demonstrated similar or enhanced replication and cell-killing efficacy of rNDV F0-M/S compared to rNDV F0 and rNDV F0-M. In conclusion, NDV F0 variants with M and S substitutions are non-virulent, effective oncolytic viruses that can be produced in mammalian cells, potentially resulting in a more effective treatment option for pancreatic cancer patients compared to rNDV F0.

项与 RSV F protein 相关的新闻（医药）

2025-01-03

·智药邦

JMC｜上海药物所徐志建团队：AI驱动的氟取代化合物的活性预测模型F-CPI

氟（F）是药物分子结构中的常见组成元素。在2022年最畅销的10种小分子药物中，有5种含有F。在DrugBank收录的2761种上市小分子药物中，共有297种含F药物（约11%）。因此，F取代是先导化合物结构优化的一种常见策略。但药物中的F既难形成氢键，也难形成典型的卤键，F取代对化合物-蛋白质相互作用（CPI）的影响仍然是一个谜，往往只能根据经验进行猜测，难以用计算模拟方法准确判断在分子的何处引入F会提高活性。近日，研究人员基于深度学习方法对F取代后化合物与蛋白质相互作用进行了研究，结合蛋白质与化合物多个模态的信息，提出了一个F取代活性预测专用模型F-CPI（图1）。较过往的机器学习算法以及主流的CPI模型相比，展现出了较高的优越性和泛用性。F-CPI用于SARS-CoV-2 3CLpro先导化合物的结构优化，F取代使分子水平抑制活性提高了100多倍（IC50: 0.23µM vs. 28.19µM）。图1. F取代化合物-蛋白质相互作用任务概览该研究成果以题为“F-CPI: A multimodal deep learning approach for predicting compound bioactivity changes induced by fluorine substitution”的文章发表于《Journal of Medicinal Chemistry》，为引入F原子进行结构优化提供了有效的工具。在这项研究中，构建了一个包含111168对F取代和原始化合物的数据集。并基于此数据集开发了一个多模态深度学习模型F-CPI（图2）。该模型结合了化合物和蛋白质多个模态的信息，包括序列信息，分子指纹，蛋白质接触图信息，位置特异性矩阵（PSSM）信息等。图2. F-CPI的模型结构与传统的机器学习（表1）和基于深度学习的CPI任务模型（表2）相比，F-CPI在准确率、精确率和召回率（~90%、~79%和~45%）上均实现了显著提升，优于随机森林（~87%，~59%，~23%）和GraphDTA（~86%、~58%和~40%）等模型。表1. 传统机器学习和F-CPI性能比较 p-emb代表预训练嵌入，&emb代表预训练和序列嵌入的结合。表2. IC50数据集上不同深度学习模型的性能比较为了探索该模型在实际应用中的潜力，研究人员进行了一系列湿实验，以检验该模型在先导化合物结构优化方面的能力。选择SARS-CoV-2 3CLpro作为靶蛋白，经计算后，选择了三对化合物进行合成和活性测试，其中(a)(b)为正样本预测验证，(c)为负样本预测验证（图3）。结果表明，三对化合物最终的活性表现都与模型预测相符。令人印象深刻的是，其中一个化合物只引入一个F原子，活性就提高了两个数量级（IC50:0.23µMvs. 28.19µM）。从所得结果来看，F-CPI有望为含F药物的发现和设计提供新思路。图3.三对化合物F取代前后的活性变化该论文第一作者为华东师范大学张倩副研究员、硕士研究生尹闻海、沈阳药科大学联合培养硕士研究生陈昕尧，通讯作者为中国科学院上海药物研究所徐志建研究员和烟台新药创制山东省实验室蒋翔锐研究员。该工作还得到中国科学院上海药物研究所朱维良研究员、沈敬山研究员和华东师范大学周爱民教授、张桂戌教授等的大力支持。该项研究工作得到了国家自然科学基金、中国科学院先导B项目、科技部重点研发项目和中国科学院上海药物研究所自主部署项目的资助。原文链接： https://doi-org.libproxy1.nus.edu.sg/10.1021/acs.jmedchem.4c02668 --------- End --------- 感兴趣的读者，可以添加小邦微信加入读者实名讨论微信群。添加时请主动注明姓名-企业-职位/岗位或姓名-学校-职务/研究方向。

临床研究

2024-12-17

·PipelineReview

Merck Announces FDA Acceptance of Biologics License Application for Clesrovimab, an Investigational Long-Acting Monoclonal Antibody Designed to Protect Infants from RSV Disease During their First RSV Season

If approved, clesrovimab has the potential to be available to help address the burden of RSV disease in the U.S. in time for the 2025-26 season RAHWAY, NJ, USA I December 16, 2024 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for clesrovimab (MK-1654), the company’s investigational prophylactic long-acting monoclonal antibody designed to protect infants from respiratory syncytial virus (RSV) disease during their first RSV season. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of June 10, 2025. “Despite recent advances in RSV prevention, unmet needs remain for additional effective interventions to help protect infants and continue to help address the burden RSV places on families and the healthcare system. This regulatory milestone, along with promising results from our pivotal studies demonstrating efficacy in the prevention of RSV disease, marks important progress toward our goal of having clesrovimab available in time for the 2025-26 RSV season,” said Dr. Paula Annunziato, senior vice president, infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories. “We look forward to working alongside the FDA on the review of clesrovimab, which, if approved, would be the first and only single dose immunization for infants regardless of weight designed to protect them for the duration of their first RSV season.” The application is supported by results from the pivotal Phase 2b/3 CLEVER trial (MK-1654-004), a randomized placebo-controlled trial evaluating a single dose of clesrovimab administered to healthy preterm and full-term infants (birth to 1 year of age), and interim results from the ongoing Phase 3 SMART trial (MK-1654-007) evaluating the safety and efficacy of clesrovimab versus palivizumab in infants and children at increased risk for severe RSV disease. Data from these trials were presented during IDWeek in October 2024. If approved, Merck anticipates that clesrovimab would be available for ordering by physicians and healthcare administrators by July 2025, with shipments to arrive in time for the 2025 RSV season. About clesrovimab (MK-1654) Clesrovimab (MK-1654) is an investigational, extended half-life monoclonal antibody (mAb) developed as a passive immunization for the prevention of RSV disease. Clesrovimab is designed to be administered as the same single dose, regardless of weight, and is being studied in healthy preterm, full-term and at-risk infants to provide direct, rapid, and durable protection through their first RSV season against mild, moderate and severe RSV. About Merck’s commitment to global supply and access of clesrovimab Since the discovery of clesrovimab, our investigational respiratory syncytial virus (RSV) monoclonal antibody (mAb), our goal has been to facilitate global access to this intervention. We are diligently developing our regulatory and access strategies, as well as our supply chain to be fit-for-purpose for low- and middle-income countries by utilizing diversified internal investments and external partnerships. The company is working with urgency to submit licensure applications to address unmet needs for RSV prevention globally. About RSV Respiratory syncytial virus (RSV) is a contagious virus that causes widespread seasonal infections like the flu, with a worldwide burden in infants and older adults. There is high unmet need for preventative options in both healthy and high-risk infants. Globally, RSV is the leading cause of hospitalization for healthy infants under a year old, and a major cause of death in low- and middle-income countries. RSV can lead to serious respiratory conditions like bronchiolitis and pneumonia, causing an estimated 3.6 million hospitalizations and 101,000 deaths a year worldwide in children under five. According to the CDC, RSV season starts in the fall and peaks in the winter in most regions of the United States, but timing and severity in a given community or region can vary year to year. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . SOURCE: Merck

临床3期上市批准申请上市

2024-12-11

·药研网

因安全问题，FDA暂停所有RSV疫苗在婴幼儿人群的临床开发

据外媒endpoints 报道，FDA 透露，目前所有针对幼儿和婴儿 RSV 疫苗的研究都已暂停，其中包括Moderna此前未披露的两项研究。 FDA周二表示，在Moderna的两款候选疫苗mRNA-1345和mRNA-1365中，观察到“重症/极重症下呼吸道感染病例的不平衡”。其中，mRNA-1345在9月因婴儿安全性问题而被终止试验。莫德纳的临床试验评估了5至8个月大的婴儿，接种剂量为15微克的任一疫苗。根据FDA数据，在对两种疫苗候选物进行评估的研究中，接受mRNA-1365疫苗的20名婴儿中，有10名后来出现了症状明显的呼吸道合胞病毒（RSV）感染，其中3例为严重或非常严重的病例。然而，在对照组的20名婴儿中，有12人后来感染了RSV，其中1例出现了严重或非常严重的病例。虽然委员会在周四的咨询委员会上不会投票，但FDA正在请外部专家讨论目前关于RSV疫苗的现有证据是否“表明潜在的安全问题更广泛地适用于婴幼儿RSV候选疫苗的评估”。截至收盘，Moderna股价大跌约9%。今年5月，美国FDA已批准呼吸道合胞病毒（RSV）mRNA疫苗mRESVIA（mRNA-1345）上市，用于保护60岁及以上成年人免受RSV感染引起的下呼吸道疾病（RSV-LRTD），该是Moderna公司第二项获批的mRNA疫苗。 End 声明：本公众号所有发文章(包括原创及转载文章)系出于传递更多信息之目的，且注明来源和作者。本公众号欢迎分享朋友圈或大群，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载/商务/投稿 | 联系微信15618157102（sum_Gmi）商务合作稿件征集点击了解详情往期回顾 1 10月 | 20家生物医药裁员汇总 2 国产首款四价HPV疫苗拟纳入优先审评 3 3. 7亿美元!今年规模最大的生物医药融资诞生

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