Antiviral research最新文献_第10页

Lipid-targeting antiviral strategies: Current state and future perspectives 脂质靶向抗病毒策略：现状与未来展望

IF 4.5 2区医学

Antiviral research Pub Date : 2025-02-11 DOI: 10.1016/j.antiviral.2025.106103

Ana-Belén Blázquez , Patricia Mingo-Casas , Ernesto Quesada , Eva María Priego , María-Jesús Pérez-Perez , Miguel A. Martín-Acebes

{"title":"Lipid-targeting antiviral strategies: Current state and future perspectives","authors":"Ana-Belén Blázquez , Patricia Mingo-Casas , Ernesto Quesada , Eva María Priego , María-Jesús Pérez-Perez , Miguel A. Martín-Acebes","doi":"10.1016/j.antiviral.2025.106103","DOIUrl":"10.1016/j.antiviral.2025.106103","url":null,"abstract":"<div><div>There is an urgent need for antiviral compounds effective against currently known and future viral threats. The development of host-targeting antivirals (HTAs) appears as an alternative strategy to fight viral infections minimizing the potential of resistant mutant development and potentially leading to the identification of broad-spectrum antiviral agents. Among the host factors explored for HTA strategy, lipids constitute an attractive target as many viruses, even genetically diverse, hijack specific lipids during their lifecycle. Multiple repurposing efforts have been performed to analyze the antiviral properties of lipid-targeting compounds. These studies include the analysis of the effects of cholesterol lowering drugs such as statins, cholesterol transport inhibitors, sphingolipid modulators, <em>de novo</em> lipogenesis inhibitors blocking fatty acid synthesis, compounds targeting glycerophospholipids or drugs interfering with lipid droplet metabolism. This review is focused on the current status of lipid-based or lipid-targeting antiviral strategies and their potential for the development of antiviral therapies, with special emphasis on those studies that have reached advanced stages of development such as efficacy studies in animal models or clinical trials. Whereas there is still a long way to go, multiple proof-of-concept studies and clinical evidence reinforce the therapeutic potential of these strategies warranting their further development into effective antiviral therapies.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"236 ","pages":"Article 106103"},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412991","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

DHODH inhibitors: What will it take to get them into the clinic as antivirals? DHODH抑制剂：怎样才能使它们作为抗病毒药物进入临床？

IF 4.5 2区医学

Antiviral research Pub Date : 2025-02-10 DOI: 10.1016/j.antiviral.2025.106099

Anna Luganini , Donatella Boschi , Marco L. Lolli , Giorgio Gribaudo

{"title":"DHODH inhibitors: What will it take to get them into the clinic as antivirals?","authors":"Anna Luganini , Donatella Boschi , Marco L. Lolli , Giorgio Gribaudo","doi":"10.1016/j.antiviral.2025.106099","DOIUrl":"10.1016/j.antiviral.2025.106099","url":null,"abstract":"<div><div>The emergence of new human viruses with epidemic or pandemic potential has reaffirmed the urgency to develop effective broad-spectrum antivirals (BSAs) as part of a strategic framework for pandemic prevention and preparedness. To this end, the host nucleotide metabolic pathway has been subject to intense investigation in the search for host-targeting agents (HTAs) with potential BSA activity. In particular, human dihydroorotate dehydrogenase (<em>h</em>DHODH), a rate-limiting enzyme in the <em>de novo</em> pyrimidine biosynthetic pathway, has been identified as a preferential target of new HTAs. Viral replication in fact relies on cellular pyrimidine replenishment, making <em>h</em>DHODH an ideal HTA target. The depletion of the host pyrimidine pool that ensues the pharmacological inhibition of <em>h</em>DHODH activity elicits effective BSA activity through three distinct mechanisms: it blocks viral DNA and RNA synthesis; it activates effector mechanisms of the host innate antiviral response; and it mitigates the virus-induced inflammatory response. However, despite the spectacular results obtained <em>in vitro</em>, the <em>h</em>DHODH inhibitors examined as mono-drug therapies in animal models of human viral infections and in clinical trials have produced disappointing levels of overall antiviral efficacy. To overcome this inherent limitation, pharmacological strategies based on multi-drug combination treatments should be considered to enable efficacy of <em>h</em>DHODH-targeted antiviral therapies.</div><div>Here, we review the state-of-the-art of antiviral applications of <em>h</em>DHODH inhibitors, discuss the challenges that have emerged from their testing in animal models and human clinical trials and consider how they might be addressed to advance the development of <em>h</em>DHODH inhibitors as BSA for the treatment of viral diseases.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"236 ","pages":"Article 106099"},"PeriodicalIF":4.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transgenic mice expressing the human CDHR3 receptor: A sensitive RV-C infection model for the evaluation of vaccines and therapeutics 表达人CDHR3受体的转基因小鼠：一种用于评估疫苗和治疗方法的敏感RV-C感染模型

IF 4.5 2区医学

Antiviral research Pub Date : 2025-02-07 DOI: 10.1016/j.antiviral.2025.106102

Zhenhong Zhou , Rui Zhu , Hongwei Yang , Weixi Deng , Zijie Zhang , Yue Li , Jiaxin Xu , Ziyang Yan , Ruoxi Wang , Sijia Chang , Zhichao Yin , Yuanyuan Wu , Dongqing Zhang , Mujin Fang , Che Liu , Yuqiong Que , Jun Zhang , Ningshao Xia , Yingbin Wang , Longfa Xu , Tong Cheng

{"title":"Transgenic mice expressing the human CDHR3 receptor: A sensitive RV-C infection model for the evaluation of vaccines and therapeutics","authors":"Zhenhong Zhou , Rui Zhu , Hongwei Yang , Weixi Deng , Zijie Zhang , Yue Li , Jiaxin Xu , Ziyang Yan , Ruoxi Wang , Sijia Chang , Zhichao Yin , Yuanyuan Wu , Dongqing Zhang , Mujin Fang , Che Liu , Yuqiong Que , Jun Zhang , Ningshao Xia , Yingbin Wang , Longfa Xu , Tong Cheng","doi":"10.1016/j.antiviral.2025.106102","DOIUrl":"10.1016/j.antiviral.2025.106102","url":null,"abstract":"<div><div>Rhinovirus C (RV-C) is the primary causative agent of severe acute respiratory illnesses (ARTIs) in infants and young children. The limited availability of animal models complicates the development of prophylactic and therapeutic strategies targeting RV-C. Previous studies have identified human cadherin-related family member 3 (hCDHR3) as the cellular receptor for RV-C, with its expression enabling previously unsusceptible cells to support both viral entry and replication. Recently, an adult hCDHR3 transgenic mouse model was developed to investigate the role of human stimulator of interferon genes (hSTING) in RV-C15 infection <em>in vivo</em>. However, adult mice do not support efficient RV-C15 infection. Here, we report a transgenic mouse line expressing hCDHR3 constitutively that is highly susceptible to early-life infections by multiple serotypes of RV-C, including RV-C15, RV-C2, and RV-C41. Neonatal transgenic mice infected with various RV-C strains via the intraperitoneal (i.p.) route exhibit similar symptoms, such as severe inflammation, limb paralysis, and death. Moreover, passive immunization with antisera or therapeutic antibodies can protect against lethal RV-C infection in these transgenic mice. Overall, this study provides a valuable animal model for the <em>in vivo</em> antiviral evaluation against RV-C.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"235 ","pages":"Article 106102"},"PeriodicalIF":4.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372309","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

Host-targeted antivirals against SARS-CoV-2 in clinical development - Prospect or disappointment? 针对SARS-CoV-2的宿主抗病毒药物的临床开发——前景还是失望？

IF 4.5 2区医学

Antiviral research Pub Date : 2025-02-07 DOI: 10.1016/j.antiviral.2025.106101

André Schreiber, Stephan Ludwig

{"title":"Host-targeted antivirals against SARS-CoV-2 in clinical development - Prospect or disappointment?","authors":"André Schreiber, Stephan Ludwig","doi":"10.1016/j.antiviral.2025.106101","DOIUrl":"10.1016/j.antiviral.2025.106101","url":null,"abstract":"<div><div>The global response to the COVID-19 pandemic, caused by the novel SARS-CoV-2 virus, has seen an unprecedented increase in the development of antiviral therapies. Traditional antiviral strategies have primarily focused on direct-acting antivirals (DAAs), which specifically target viral components. In recent years, increasing attention was given to an alternative approach aiming to exploit host cellular pathways or immune responses to inhibit viral replication, which has led to development of so-called host-targeted antivirals (HTAs). The emergence of SARS-CoV-2 and COVID-19 has promoted a boost in this field. Numerous HTAs have been tested and demonstrated their potential against SARS-CoV-2 through <em>in vitro</em> and <em>in vivo</em> studies. However, in striking contrast, only a limited number have successfully progressed to advanced clinical trial phases (2–4), and even less have entered clinical practice. This review aims to explore the current landscape of HTAs targeting SARS-CoV-2 that have reached phase 2–4 clinical trials. Additionally, it will explore the challenges faced in the development of HTAs and in gaining regulatory approval and market availability.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"235 ","pages":"Article 106101"},"PeriodicalIF":4.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting PI4KB and Src/Abl host kinases as broad-spectrum antiviral strategy: Myth or real opportunity? 靶向PI4KB和Src/Abl宿主激酶作为广谱抗病毒策略：神话还是真正的机会？

IF 4.5 2区医学

Antiviral research Pub Date : 2025-02-06 DOI: 10.1016/j.antiviral.2025.106100

Maria Grazia Martina , Daniele Rubini , Marco Radi , Valeria Cagno

{"title":"Targeting PI4KB and Src/Abl host kinases as broad-spectrum antiviral strategy: Myth or real opportunity?","authors":"Maria Grazia Martina , Daniele Rubini , Marco Radi , Valeria Cagno","doi":"10.1016/j.antiviral.2025.106100","DOIUrl":"10.1016/j.antiviral.2025.106100","url":null,"abstract":"<div><div>Viruses pose a continuous threat to human health. Limited treatment options exist for current viruses, and the risk of infections with newly emerging or re-emerging viruses is increasing. In a pandemic scenario, having a broad-spectrum antiviral to limit viral spread while developing specific antivirals and vaccines is crucial. Targeting host kinases represents a valuable strategy due to the higher barrier to resistance and the broad-spectrum activity it offers. While cells have redundant kinases for the same biological function, viruses rely on specific kinases for their replication cycle, enabling targeted antiviral action with limited toxicity.</div><div>This review focuses on two extensively studied kinase targets: the lipid kinase phosphatidylinositol 4-kinase IIIβ (PI4KB) and the tyrosine kinase proteins Src and Abl. Compounds active against these targets are reviewed in terms of the viruses they inhibit, their mechanisms of action and their stage of development. While PI4KB inhibitors have reached clinical trials, those targeting Src and Abl remain largely in the preclinical phase. Nevertheless, opportunities exist to improve potency and further understand the specific roles of these kinases in the life cycle of multiple viruses.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"235 ","pages":"Article 106100"},"PeriodicalIF":4.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ginkgolic acid inhibits Ebola virus transcription and replication by disrupting the interaction between nucleoprotein and VP30 protein 银杏酸通过破坏核蛋白与VP30蛋白的相互作用抑制埃博拉病毒的转录和复制。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2024.106074

Chiwei Peng , Fang Wu , Yanhong Ma , Guolong Liu , Yin Huang , Rongbiao Tong , Wei Xu

{"title":"Ginkgolic acid inhibits Ebola virus transcription and replication by disrupting the interaction between nucleoprotein and VP30 protein","authors":"Chiwei Peng , Fang Wu , Yanhong Ma , Guolong Liu , Yin Huang , Rongbiao Tong , Wei Xu","doi":"10.1016/j.antiviral.2024.106074","DOIUrl":"10.1016/j.antiviral.2024.106074","url":null,"abstract":"<div><div>The Ebola virus, a filovirus, has been responsible for significant human fatalities since its discovery. Despite extensive research, effective small-molecule drugs remain elusive due to its complex pathogenesis. Inhibition of RNA synthesis is a promising therapeutic target, and the VP30 protein plays a critical role in this process. The interaction between VP30 and the nucleoprotein (NP) is essential for viral replication. We identified ginkgolic acid as a small molecule with strong affinity for VP30, which was validated through multiple assays, including thermal shift, surface plasmon resonance, fluorescence polarization, pull-down, and co-immunoprecipitation. The antiviral efficacy of ginkgolic acid was demonstrated in the EBOV transcription- and replication-competent virus-like particle (trVLP) system. Furthermore, we resolved the crystal structure of the VP30-ginkgolic acid complex, revealing two ginkgolic acid molecules located at the VP30/NP interaction interface. This structural information provides insight into the molecular basis of ginkgolic acid's antiviral activity and suggests a novel therapeutic strategy targeting the VP30/NP interaction.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"234 ","pages":"Article 106074"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880682","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

Intranasal exposure to commensal bacterium Rothia mucilaginosa protects against influenza A virus infection 鼻内接触黏液罗氏共生菌可预防甲型流感病毒感染。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2025.106076

Ana Raquel Maia , Loïc Gonzalez , Badreddine Bounab , Lucia Grassi , Coralie Mousset , Gaëlle Fromont-Hankard , Adeline Cezard , Pieter Hiemstra , Thomas Baranek , Christophe Paget , Aurélie Crabbé , Mustapha Si-Tahar

{"title":"Intranasal exposure to commensal bacterium Rothia mucilaginosa protects against influenza A virus infection","authors":"Ana Raquel Maia , Loïc Gonzalez , Badreddine Bounab , Lucia Grassi , Coralie Mousset , Gaëlle Fromont-Hankard , Adeline Cezard , Pieter Hiemstra , Thomas Baranek , Christophe Paget , Aurélie Crabbé , Mustapha Si-Tahar","doi":"10.1016/j.antiviral.2025.106076","DOIUrl":"10.1016/j.antiviral.2025.106076","url":null,"abstract":"<div><div>The respiratory tract hosts a diverse microbial community whose composition varies with anatomical location and throughout life. <em>Rothia mucilaginosa</em>, a common commensal of the upper respiratory tract and oral cavity, has recently been recognized for its ability to inhibit bacteria-triggered pro-inflammatory responses. However, its role in modulating the immune response to viral infections such as influenza A virus (IAV) pneumonia, remains unknown. Here, we demonstrate that <em>R. mucilaginosa</em> enhances protection against IAV, promoting viral clearance, reducing inflammation, preserving bronchial and alveolar structures, and improving survival in a mouse model of influenza pneumonia. The enhanced viral clearance observed in <em>R. mucilaginosa</em>-treated mice is associated with the recruitment of innate immune cells to the lungs, including PD-L1-expressing neutrophils, alongside the production of the anti-inflammatory cytokine IL-10, both of which are known to play regulatory roles in the context of IAV infection. Together, these findings highlight <em>R. mucilaginosa</em>-mediated innate immune priming as a key protective mechanism in the respiratory tract against IAV infection.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"234 ","pages":"Article 106076"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and optimization of an mRNA-vectored single-chain IgA1 isotype monoclonal antibody with potential to treat or prevent dengue virus infection 具有治疗或预防登革热病毒感染潜力的mrna载体单链IgA1同型单克隆抗体的研制和优化

IF 4.5 2区医学

Antiviral research Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2025.106078

Thanh Nguyen , Chad Gebo , Joseph Lu , David O. Popoola , Stephen J. Thomas , Yamin Li , Adam T. Waickman

{"title":"Development and optimization of an mRNA-vectored single-chain IgA1 isotype monoclonal antibody with potential to treat or prevent dengue virus infection","authors":"Thanh Nguyen , Chad Gebo , Joseph Lu , David O. Popoola , Stephen J. Thomas , Yamin Li , Adam T. Waickman","doi":"10.1016/j.antiviral.2025.106078","DOIUrl":"10.1016/j.antiviral.2025.106078","url":null,"abstract":"<div><div>Dengue virus (DENV) is a rapidly expanding infectious disease threat that causes an estimated 100 million symptomatic infections every year. A barrier to preventing DENV infections with traditional vaccines or prophylactic monoclonal antibody (mAb) therapies is the phenomenon of Antibody-Dependent Enhancement (ADE), wherein sub-neutralizing levels of DENV-specific IgG antibodies can enhance infection and pathogenesis rather than providing protection from disease. Fortunately, IgG is not the only antibody isotype capable of binding and neutralizing DENV, as DENV-specific IgA1 isotype mAbs can bind and neutralize DENV while without exhibiting any ADE activity. However, the development of IgA1-based mAb therapies is currently hindered by inefficient <em>in vitro</em> expression systems and the lack of saleable purification platforms. Accordingly, alternative delivery modalities are required to realize the therapeutic potential of IgA-based infectious-disease therapies. In this study we describe the development and optimization of a DENV-specific single-chain IgA construct that retains the desirable biological properties of the parental IgA mAb yet is compatible with efficient <em>in vivo</em> delivery with a novel/liver-tropic lipid nanoparticle. We propose that this platform is uniquely and exceptionally well suited for preventing and/or treating DENV infections and may have broad applicability in the greater infectious disease space in situations where the use of IgG isotype mAbs may be counterindicated.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"234 ","pages":"Article 106078"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943367","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

Serum O-glycosylated HBsAg levels correlate with HBV RNA in HBeAg positive CHB patients during antiviral therapy 在HBeAg阳性CHB患者抗病毒治疗期间，血清o -糖化HBsAg水平与HBV RNA相关。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-02-01 DOI: 10.1016/j.antiviral.2025.106077

Bilian Yao , Qi Xu , Yousuke Yamada , Kiyohiko Angata , Yan Zhang , Hisashi Narimatsu , Demin Yu , Xinxin Zhang

{"title":"Serum O-glycosylated HBsAg levels correlate with HBV RNA in HBeAg positive CHB patients during antiviral therapy","authors":"Bilian Yao , Qi Xu , Yousuke Yamada , Kiyohiko Angata , Yan Zhang , Hisashi Narimatsu , Demin Yu , Xinxin Zhang","doi":"10.1016/j.antiviral.2025.106077","DOIUrl":"10.1016/j.antiviral.2025.106077","url":null,"abstract":"<div><h3>Background</h3><div>Recent evidence has indicated that the <em>O</em>-glycosylated PreS2 domain of the middle HBsAg is a distinguishing characteristic that allows the identification of HBsAg of HBV Dane particles and SVPs. This study's objective was to assess the changes in serum <em>O</em>-glycosylated HBsAg levels in CHB patients undergoing ETV or Peg-IFNα treatment.</div></div><div><h3>Methods</h3><div>Our retrospective study enrolled 86 patients with genotype C CHB. We determined the <em>O</em>-glycosylated HBsAg, HBsAg, HBeAg, HBV DNA, and HBV RNA at baseline and during ETV or Peg-IFNα treatment. The correlations between <em>O-</em>glycosylated HBsAg and conventional HBV marker levels were also examined. Furthermore, we performed a ROC analysis to evaluate the predictive value of individual biomarkers for virological response.</div></div><div><h3>Results</h3><div>At baseline, the serum <em>O-</em>glycosylated HBsAg levels were significantly correlated with the HBsAg (r = 0.754), HBV DNA (r = 0.498), HBeAg (r = 0.404), and HBV RNA (r = 0.399) in HBeAg positive patients. <em>O</em>-glycosylated HBsAg decreased after antiviral therapy. Both <em>O</em>-glycosylated HBsAg and HBsAg were significantly correlated with serum HBV DNA as well as HBV RNA at baseline, while only <em>O</em>-glycosylated HBsAg still correlated with HBV RNA (r = 0.397) in DNA-undetectable patients after ETV therapy. <em>O</em>-glycosylated HBsAg was significantly correlated with HBV RNA (r = 0.846) in DNA-undetectable patients after Peg-IFNα therapy compared to that of HBsAg (r = 0.800).</div></div><div><h3>Conclusion</h3><div>Serum <em>O-</em>glycosylated HBsAg level decreased during anti-viral therapy and correlated well with conventional HBV markers in HBeAg positive genotype C patients, suggesting that it could be a potential monitoring biomarker in HBV DNA-suppressed patients.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"234 ","pages":"Article 106077"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943368","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

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

Antiviral research 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

{"title":"Discovery and development of INNA-051, a TLR2/6 agonist for the prevention of complications resulting from viral respiratory infections","authors":"Francesca A. Mercuri , Gary P. Anderson , Bruce E. Miller , Christophe Demaison , Ruth Tal-Singer","doi":"10.1016/j.antiviral.2024.106063","DOIUrl":"10.1016/j.antiviral.2024.106063","url":null,"abstract":"<div><div>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. <em>In vivo</em> 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.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"234 ","pages":"Article 106063"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0