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Discovery and development of INNA-051, a TLR2/6 agonist for the prevention of complications resulting from viral respiratory infections 用于预防病毒性呼吸道感染并发症的TLR2/6激动剂INNA-051的发现和开发。
IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2024.106063
Francesca A. Mercuri , Gary P. Anderson , Bruce E. Miller , Christophe Demaison , Ruth Tal-Singer
Viral respiratory infection is associated with significant morbidity and mortality. The diversity of viruses implicated, coupled with their propensity for mutation, ignited an interest in host-directed antiviral therapies effective across a wide range of viral variants. Toll-like receptors (TLRs) are potential targets for the development of broad-spectrum antivirals given their central role in host immune defenses. Synthetic agonists of TLRs have been shown to boost protective innate immune responses against respiratory viruses. However, clinical success was hindered by short duration of benefit and/or induction of systemic adverse effects. INNA-051, a TLR2/6 agonist, is in development as an intranasal innate immune enhancer for prophylactic treatment in individuals at risk of complications resulting from respiratory viral infections. In vivo animal studies demonstrated the efficacy as prophylaxis against multiple viruses including SARS-CoV-2, influenza, and rhinovirus. Early clinical trials demonstrated an acceptable safety and tolerability profile. Intranasal delivery to the primary site of infection in humans induced a local innate host defense response characterized by innate immune cell infiltration into the nasal epithelium and activation and antiviral response genes. Taken together, the preclinical and clinical data on INNA-051 support further investigation of its use in community infection settings.
病毒性呼吸道感染与显著的发病率和死亡率相关。所涉及的病毒的多样性,加上它们的突变倾向,激发了人们对宿主定向抗病毒疗法的兴趣,这种疗法对广泛的病毒变体有效。toll样受体(TLRs)是开发广谱抗病毒药物的潜在靶点,因为它们在宿主免疫防御中起着核心作用。tlr的合成激动剂已被证明可以增强对呼吸道病毒的保护性先天免疫反应。然而,临床成功受到持续时间短和/或诱导全身不良反应的阻碍。INNA-051是一种TLR2/6激动剂,正在开发作为鼻内先天免疫增强剂,用于有呼吸道病毒感染并发症风险的个体的预防性治疗。在体内动物实验中证明了对多种病毒的预防效果,包括SARS-CoV-2、流感和鼻病毒。早期临床试验表明其安全性和耐受性可接受。经鼻给药到人类感染的原发部位诱导了局部先天宿主防御反应,其特征是先天免疫细胞浸润到鼻上皮,激活和抗病毒反应基因。综上所述,INNA-051的临床前和临床数据支持进一步调查其在社区感染环境中的使用。
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引用次数: 0
Corrigendum to “Circulating capsid-antibody-complexes (CACs) drive intrahepatic complement deposition and inform subclinical liver inflammation in chronic hepatitis B” [Antivi. Res. 231 (2024) 1–13/106017] “循环衣壳抗体复合物(CACs)驱动肝内补体沉积并告知慢性乙型肝炎的亚临床肝脏炎症”的更正[Antivi]。Res. 231(2024) 1-13/106017]。
IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2025.106080
Yijie Tang , Mingzhu Xu , Cong Wang , Min Wu , Lyuyin Hu , Jin Li , Wei Lu , Ye Zheng , Min Zhang , Xizi Jiang , Chuanwu Zhu , Jennifer Audsley , Pisit Tangkijvanich , Anchalee Avihingsanon , Shu Song , Shuangzhe Liu , Sharon R. Lewin , Jacob George , Mark Douglas , Yun Ling , Xiaonan Zhang
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引用次数: 0
Novel reporter constructs to accelerate antiviral and therapeutic discovery for Enterovirus-A71 加速肠道病毒-A71 抗病毒和治疗发现的新型报告构建体。
IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2025.106094
William Bakhache , Ann Shen , Walker Symonds-Orr , Megan Culler Freeman , Patrick T. Dolan
Enterovirus A71 (EV-A71) is an important human pathogen and ‘prototype pathogen’ for studies of other Enteroviruses of pandemic potential. Understanding the biology of EV-A71 would inform generalizable strategies for antiviral drug, vaccine, and monoclonal antibody development. Such studies are accelerated by robust reagents to evaluate efficacy. Here, we describe and evaluate a suite of synthetic reporter constructs to accelerate EV-A71 research and therapeutic discovery. These constructs include replicons and infectious clones carrying luminescent and fluorescent reporter proteins. Among the reporters we tested were shorter luminescent and de novo-designed synthetic fluorescent proteins, which enhance genetic stability, reduce reporter gene loss and improve the utility of these reporters. This toolbox provides free access to robust and flexible assays for EV-A71 infection and replication through public repositories, promoting and accelerating open scientific discovery for this understudied emerging pathogen.
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引用次数: 0
Antiviral effect of pinostrobin, a bioactive constituent of Boesenbergia rotunda, against porcine epidemic diarrhea virus 猪流行性腹泻病毒的抗病毒作用。
IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2024.106073
Nopporn Chutiwitoonchai , Radeekorn Akkarawongsapat , Suphat Chantawarin , Chutima Jiarpinitnun , Benjamas Liwnaree , Samaporn Teeravechyan , Sunhapas Soodvilai
Global swine industry has long been severely affected by the periodic outbreaks of porcine epidemic diarrhea (PED), a deadly infectious disease in piglets caused by the porcine epidemic diarrhea virus (PEDV). Currently, available vaccines and antiviral drugs could not provide effective prevention and treatment of PEDV infection in pigs. In this study, Boesenbergia rotunda (B. rotunda) extract and its major bioactive flavonoid, pinostrobin, were demonstrated to exhibit remarkable anti-PEDV activities with EC50 values of 0.33 ± 0.02 μg/ml and 2.71 ± 0.12 μM, and selectivity indices (SI) of 11.93 and > 184.55, respectively. Results based on a time-of-addition assay showed that pinostrobin blocked PEDV infection mainly at the early stages of infection. More specifically, pinostrobin reduced cell-cell fusion mediated by the viral spike protein, suggesting that the compound may target the virus fusion step. We also synthesized pinostrobin derivatives and explored the impact of pinostrobin structural features to the observed anti-PEDV activity. Results indicated the importance of the hydroxyl group and substituent on the phenyl ring. In summary, this study highlights the potential of B. rotunda extract and its bioactive compound, pinostrobin, as candidates for the development of antiviral drugs to more effectively control PEDV infection.
猪流行性腹泻(PED)是由猪流行性腹泻病毒(PEDV)引起的仔猪致命传染病,长期以来,全球养猪业受到周期性暴发的严重影响。目前,现有的疫苗和抗病毒药物还不能有效预防和治疗猪PEDV感染。在本研究中,圆形圆叶草(B. rotunda)提取物及其主要生物活性类黄酮pinostrobin具有显著的抗pedv活性,其EC50值分别为0.33±0.02 μg/ml和2.71±0.12 μM,选择性指数(SI)分别为11.93和bb0 184.55。基于添加时间测定的结果显示,pinostrobin主要在感染的早期阶段阻断PEDV感染。更具体地说,pinostrobin减少了由病毒刺突蛋白介导的细胞-细胞融合,表明该化合物可能靶向病毒融合步骤。我们还合成了pinostrobin衍生物,并探讨了pinostrobin结构特征对观察到的抗pedv活性的影响。结果表明苯基环上羟基和取代基的重要性。综上所述,本研究强调了圆圆b提取物及其生物活性化合物pinostrobin作为开发抗病毒药物的候选物的潜力,以更有效地控制PEDV感染。
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引用次数: 0
HBV serum RNA kinetics during nucleic acid polymers based therapy predict functional cure HBV血清RNA动力学在核酸聚合物为基础的治疗预测功能治愈。
IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2024.106061
Leeor Hershkovich , Scott J. Cotler , Louis Shekhtman , Michel Bazinet , Mark Anderson , Mary Kuhns , Gavin Cloherty , Andrew Vaillant , Harel Dahari
Serum HBV-RNA is proposed to be a circulating marker of cccDNA transcriptional activity in hepatocytes. The combination of tenofovir-disoproxil-fumarate (TDF) and pegylated-interferon-alpha-2a (pegIFN) with nucleic-acid polymer (NAP) treatment was associated with a relatively high rate of functional cure (FC) 48 weeks after discontinuation of all therapy. We aim to characterize HBV RNA kinetics under TDF and pegIFN ± NAP combination therapies. Forty participants with chronic HBV in the REP401 phase-II clinical trial received 48 weeks of triple combination therapy with NAPs, pegIFN, and TDF. For 20 participants, triple combination therapy (TDF + pegIFN + NAPs) followed 24 weeks of TDF. For 20 other participants, triple combination therapy followed 24 weeks of TDF monotherapy and 24 weeks of dual therapy (TDF + pegIFN). The Abbott RUO assay for HBV RNA (LLoQ = 1.65 logU/mL) was performed every 4 weeks. Previously unrecognized HBV RNA kinetic patterns were identified with dual/triple therapy including (i) no change (ii) an increase followed by a new elevated plateau (only under dual therapy) and (iii) a transient increase followed by a spontaneous decline. All participants establishing a new elevated HBV RNA plateau level experienced a subsequent monophasic decline following the introduction of NAPs. Failure to reach HBV RNA LLoQ by 16 weeks of triple therapy had a negative predictive value of 100% for FC. The median HBV RNA half-life for participants in the virological-rebound group was significantly (p = 0.01) longer than in the partial and FC groups (5.7 vs 2.7 weeks, respectively). Achieving partial/functional cure is associated with a shorter HBV RNA half-life, which could reflect faster inactivation of cccDNA transcriptional activity.
血清HBV-RNA (seRNA)被认为是肝细胞中cccDNA转录活性的循环标志物。替诺福韦-富马酸二吡呋酯(TDF)和聚乙二醇干扰素- α -2a (pegIFN)联合核酸聚合物(NAP)治疗与停止所有治疗48周后相对较高的功能治愈率(FC)相关。我们的目标是表征TDF和pegIFN±NAP联合治疗下seRNA动力学。在REP401 ii期临床试验中,40名慢性HBV患者接受了48周的nap、pegIFN和TDF三联治疗。对于20名参与者,三联疗法(TDF+pegIFN+ nap)随访24周TDF。对于其他20名参与者,三联疗法遵循24周的TDF单药治疗和24周的双重治疗(TDF+pegIFN)。每4周进行abbot RUO检测HBV RNA (LLoQ=1.65 logU/mL)。以前未被识别的seRNA动力学模式在双/三联治疗中被发现,包括(i)没有变化;(ii) seRNA增加后出现新的高原升高(仅在双治疗下);(iii)短暂增加后自发下降。所有建立新的高seRNA平台水平的参与者在引入nap后经历了随后的单相下降。三联治疗16周后未能达到seRNA LLoQ,对FC的阴性预测值为100%。病毒学反弹组参与者的中位seRNA半衰期显著(p=0.01)长于部分组和FC组(分别为5.7周和2.7周)。实现部分/功能性治愈与较短的seRNA半衰期相关,这可能反映了cccDNA转录活性的更快失活。
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引用次数: 0
Seeking innovative concepts in development of antiviral drug combinations 寻求开发抗病毒药物组合的创新概念。
IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2025.106079
Denis E. Kainov , Erlend Ravlo , Aleksandr Ianevski
Antiviral drugs are crucial for managing viral infections, but current treatment options remain limited, particularly for emerging viruses. These drugs can be classified based on their chemical composition, including neutralizing antibodies (nAbs), recombinant human receptors (rhRs), antiviral CRISPR/Cas systems, interferons, antiviral peptides (APs), antiviral nucleic acid polymers, and small molecules. Some of these agents target viral factors, host factors, or both. A major challenge for virus-targeted treatments is their narrow-spectrum effectiveness and the potential for drug resistance, while host-directed and virus/host-targeted therapies often suffer from significant side effects. The synergistic combination of multiple antiviral drugs holds promise for improving treatment outcomes by targeting different stages of the viral life cycle, reducing resistance, and minimizing side effects. However, developing such drug combinations presents its own set of challenges. Several drug combinations could be optimized, and new combinations developed by using AI, to more effectively treat both emerging and re-emerging viral infections.
抗病毒药物对控制病毒感染至关重要,但目前的治疗选择仍然有限,特别是对新出现的病毒。这些药物可以根据其化学成分进行分类,包括中和抗体(nab)、重组人受体(rrs)、抗病毒CRISPR/Cas系统、干扰素、抗病毒肽(APs)、抗病毒核酸聚合物和小分子。其中一些药物针对病毒因子、宿主因子,或两者兼而有之。病毒靶向治疗的一个主要挑战是其窄谱有效性和潜在的耐药性,而宿主靶向和病毒-宿主靶向治疗往往具有显著的副作用。多种抗病毒药物的协同组合有望通过针对病毒生命周期的不同阶段,减少耐药性和最小化副作用来改善治疗效果。然而,开发这样的药物组合有其自身的一系列挑战。利用积累的知识,可以优化几种药物组合,并开发新的组合,以更有效地治疗新发和再发病毒感染。
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引用次数: 0
Design, synthesis, and biological evaluation of novel 2′-deoxy-2′-spirooxetane-7-deazapurine nucleoside analogs as anti-SARS-CoV-2 agents 新型抗sars - cov -2药物2'-脱氧-2'-螺环西烷-7-去氮杂嘌呤核苷类似物的设计、合成和生物学评价
IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2024.106060
Minli Gao , Zhaoyong Zhang , Guoqiang Yao , Lu Zhang , Anna Duan , Yuanyuan Zhang , Yanqun Wang , Jincun Zhao , Jiancun Zhang
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global public health crisis and continues to pose grave threats to human health. The efficacy of current vaccines and therapeutics is likely limited for future emerging strains due to the highly mutative nature of the virus, underscoring an urgent need for the development of new, potent antiviral agents. In this study, we report the design and synthesis of a series of novel 2′-deoxy-2′-spirooxetane-7-deazapurine nucleoside analogs as potential inhibitors of SARS-CoV-2 replication. Some of these compounds demonstrate potent antiviral activity, offering a potential new weapon for therapeutic intervention against the ever-evolving SARS-CoV-2 virus. Among the tested compounds, nucleoside analog 11q exhibited the most potent antiviral activity against SARS-CoV-2 in Vero E6 cells, with IC50 values of 0.14 μM for the wild-type strain and 0.36 μM for the BA.5 strain. Notably, compound 11q exhibits up to nine times greater inhibitory activity against wild-type SARS-CoV-2 compared to Remdesivir and also possesses a superior selectivity index. These findings suggest that compound 11q is a highly promising lead candidate for future drug development aimed at combating SARS-CoV-2.
由严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起的2019冠状病毒病(COVID-19)大流行造成了前所未有的全球公共卫生危机,并继续对人类健康构成严重威胁。由于病毒的高度突变性质,目前的疫苗和治疗方法对未来新出现的毒株的效力可能有限,因此迫切需要开发新的强效抗病毒药物。在这项研究中,我们设计和合成了一系列新的2'-脱氧-2'-螺环西烷-7-去氮杂嘌呤核苷类似物,作为SARS-CoV-2复制的潜在抑制剂。其中一些化合物显示出强大的抗病毒活性,为治疗干预不断演变的SARS-CoV-2病毒提供了潜在的新武器。在所测试的化合物中,核苷类似物11q在Vero E6细胞中表现出最有效的抗病毒活性,野生型菌株的IC50值为0.14 μM, BA.5菌株的IC50值为0.36 μM。值得注意的是,化合物11q对野生型SARS-CoV-2的抑制活性比Remdesivir高9倍,并且具有优越的选择性指数。这些发现表明,化合物11q是未来用于对抗SARS-CoV-2的药物开发的极有希望的主要候选药物。
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引用次数: 0
Nucleotide analogues and mpox: Repurposing the repurposable 核苷酸类似物和Mpox:重新利用可重新利用的。
IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2024.106057
Ashleigh Shannon, Bruno Canard
While the COVID-19 crisis is still ongoing, a new public health threat has emerged with recent outbreaks of monkeypox (mpox) infections in Africa. Mass vaccination is not currently recommended by the World Health Organization (WHO), and antiviral treatments are yet to be specifically approved for mpox, although existing FDA-approved drugs (Tecovirimat, Brincidofovir, and Cidofovir) may be used in severe cases or for immunocompromised patients. A first-line of defense is thus drug repurposing, which was heavily attempted against SARS-CoV-2 - albeit with limited success. This review focuses on nucleoside analogues as promising antiviral candidates for targeting of the viral DNA-dependent DNA polymerase. In contrast to broad-spectrum screening approaches employed for SARS-CoV-2, we emphasize the importance of understanding the structural specificity of viral polymerases for rational selection of potential candidates. By comparing DNA-dependent DNA polymerases with other viral polymerases, we highlight the unique features that influence the efficacy and selectivity of nucleoside analogues. These structural insights provide a framework for the preselection, repurposing, optimization, and design of nucleoside analogues, aiming to accelerate the development of targeted antiviral therapies for mpox and other viral infections.
虽然COVID-19危机仍在继续,但最近在非洲爆发猴痘感染,从而出现了新的公共卫生威胁。世界卫生组织(世卫组织)目前不建议大规模接种疫苗,尽管现有的fda批准的药物(Tecovirimat、Brincidofovir和Cidofovir)可用于严重病例或免疫功能低下患者,但抗病毒治疗尚未专门批准用于m痘。因此,第一道防线是药物再利用,这是针对SARS-CoV-2的大量尝试,尽管收效甚微。本文综述了核苷类似物作为靶向病毒DNA依赖性DNA聚合酶的有前途的抗病毒候选物。与SARS-CoV-2采用的广谱筛选方法相比,我们强调了解病毒聚合酶的结构特异性对于合理选择潜在候选物的重要性。通过比较DNA依赖的DNA聚合酶与其他病毒聚合酶,我们强调了影响核苷类似物的功效和选择性的独特特征。这些结构见解为核苷类似物的预选、再利用、优化和设计提供了一个框架,旨在加速针对m痘和其他病毒感染的靶向抗病毒治疗的发展。
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引用次数: 0
Host-targeting antivirals for chronic viral infections of the liver 肝脏慢性病毒感染的宿主靶向抗病毒药物
IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2024.106062
Nicola Frericks , Mara Klöhn , Frauke Lange , Lilli Pottkämper , Arnaud Carpentier , Eike Steinmann
Infection with one or several of the five known hepatitis viruses is a leading cause of liver disease and poses a high risk of developing hepatocellular carcinoma upon chronic infection. Chronicity is primarily caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) and poses a significant health burden worldwide. Co-infection of chronic HBV infected patients with hepatitis D virus (HDV) is less common but is marked as the most severe form of chronic viral hepatitis. Hepatitis A virus (HAV) and hepatitis E virus (HEV) primarily cause self-limiting acute hepatitis. However, studies have also reported chronic progression of HEV disease in immunocompromised patients. While considerable progress has been made in the treatment of HCV and HBV through the development of direct-acting antivirals (DAAs), challenges including drug resistance, incomplete viral suppression resulting in failure to achieve clearance and the lack of effective treatment options for HDV and HEV remain. Host-targeting antivirals (HTAs) have emerged as a promising alternative approach to DAAs and aim to disrupt virus-host interactions by modulating host cell pathways that are hijacked during the viral replication cycle. The aim of this review is to provide a comprehensive overview about the major milestones in research and development of HTAs for chronic HBV/HDV and HCV infections. It also summarizes the current state of knowledge on promising host-targeting therapeutic options against HEV infection.
感染五种已知肝炎病毒中的一种或几种是肝脏疾病的主要原因,慢性感染后发展为肝细胞癌的风险很高。慢性主要由乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)引起,在世界范围内造成重大健康负担。慢性乙型肝炎病毒感染患者同时感染丁型肝炎病毒(HDV)的情况较少见,但被认为是最严重的慢性病毒性肝炎。甲型肝炎病毒(HAV)和戊型肝炎病毒(HEV)主要引起自限性急性肝炎。然而,研究也报道了免疫功能低下患者的HEV疾病慢性进展。虽然通过开发直接作用抗病毒药物(DAAs),在治疗HCV和HBV方面取得了相当大的进展,但挑战仍然存在,包括耐药性、病毒抑制不完全导致无法实现清除以及缺乏针对HDV和HEV的有效治疗方案。宿主靶向抗病毒药物(hta)已成为DAAs的一种有希望的替代方法,旨在通过调节病毒复制周期中被劫持的宿主细胞途径来破坏病毒与宿主的相互作用。本综述的目的是全面概述慢性HBV/HDV和HCV感染的hta研究和开发的主要里程碑。它还总结了目前针对HEV感染的有希望的宿主靶向治疗方案的知识状况。
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引用次数: 0
Analysis of mechanisms of the rabies virus P protein-nucleocapsid interaction using engineered N-protein peptides and potential applications in antivirals design 利用工程化n蛋白肽分析狂犬病毒P蛋白-核衣壳相互作用机制及其在抗病毒药物设计中的潜在应用
IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2024.106075
Jingyu Zhan , Shatabdi Chakraborty , Ashish Sethi , Yee-Foong Mok , Fei Yan , Gregory W. Moseley , Paul R. Gooley
The Phosphoprotein (P protein) of the rabies virus has multiple roles in virus replication. A critical function is to act as a cofactor in genome replication and mRNA production through binding via its N-terminal region to the L protein, the essential enzyme for mRNA and genome synthesis/processing, and via its C-terminal domain (PCTD) to the N protein and viral RNA (N-RNA) ribonucleoprotein complex. The binding site of the PCTD on the N protein is a disordered loop that is expected to be phosphorylated at Ser389. This interface may provide novel targets for antiviral approaches. Following an alanine scan of the peptide we selected two single site mutations that showed improved affinity and combined these mutations with a phosphomimetic (S389E) to produce double and triple mutants in the context of linear and cyclic peptides of the disordered loop, with the goal of generating a competitive peptide against the N-RNA complex. To assess the binding properties of the peptides we characterized their thermodynamics identifying complex properties of improved enthalpy but with compensating entropy for mutants and cyclized peptides. Nevertheless, a triple mutant shows 3.5-fold stronger affinity for PCTD than the full-length S389E N protein. Structural characterization of the triple mutant suggests the improved affinity may be due to trapping a favoured β-strand structure for binding to the PCTD. This novel peptide may serve as a template for the future design of antivirals.
狂犬病毒的磷蛋白(P蛋白)在病毒复制过程中具有多种作用。一个关键的功能是通过其N端区域结合到L蛋白(mRNA和基因组合成/加工的必需酶),并通过其c端结构域(PCTD)结合到N蛋白和病毒RNA (N-RNA)核糖核蛋白复合物,从而在基因组复制和mRNA产生中充当辅助因子。PCTD在N蛋白上的结合位点是一个无序环,预计会在Ser389位点磷酸化。该界面可能为抗病毒方法提供新的靶点。在对肽进行丙氨酸扫描后,我们选择了两个具有改善亲和力的单位点突变,并将这些突变与拟磷基因(S389E)结合,在无序环的线性肽和环状肽的背景下产生双突变和三突变,目的是产生与N-RNA复合物竞争的肽。为了评估肽的结合特性,我们表征了它们的热力学特性,确定了改进焓的复杂特性,但对突变体和环化肽具有补偿熵。然而,三突变体对PCTD的亲和力比全长s389en蛋白强3.5倍。三重突变体的结构特征表明,亲和性的提高可能是由于捕获了与PCTD结合的有利β链结构。这种新型肽可以作为未来抗病毒药物设计的模板。
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引用次数: 0
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Antiviral research
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