Antiviral research最新文献

{"title":"α-Glucosidase inhibitors as broad-spectrum antivirals: Current knowledge and future prospects","authors":"James WJ. Kang , Kitti Wing Ki Chan , Subhash G. Vasudevan , Jenny G. Low","doi":"10.1016/j.antiviral.2025.106147","DOIUrl":"10.1016/j.antiviral.2025.106147","url":null,"abstract":"","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"238 ","pages":"Article 106147"},"PeriodicalIF":4.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690951","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}

{"title":"Corrigendum to “IgA class switching enhances neutralizing potency against SARS-CoV-2 by increased antibody hinge flexibility” [Antiv. Res. (2025) 106082]","authors":"Mengxin Xu , Zhaoyong Zhang , Yuzhu Sun , Haoting Mai , Siqi Liu , Shuning Liu , Kexin Lv , Feiyang Yu , Yuanyuan Wang , Xinyu Yue , Jiayi Zhang , Xiaoyu Cai , Ruixin Zhao , Hongjie Lu , Lin Liu , Huanle Luo , Haiyan Zhao , Yanqun Wang , Peng Gong , Shoudeng Chen , Yao-Qing Chen","doi":"10.1016/j.antiviral.2025.106146","DOIUrl":"10.1016/j.antiviral.2025.106146","url":null,"abstract":"","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106146"},"PeriodicalIF":4.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673344","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":"Hepato-selective dihydroquinolizinones active against hepatitis A virus in vitro and in vivo","authors":"Ichiro Misumi ,&nbsp;Zhizhou Yue ,&nbsp;Zhengyuan Jiang ,&nbsp;Anilkumar Karampoori ,&nbsp;Jason K. Whitmire ,&nbsp;John M. Cullen ,&nbsp;Timothy Block ,&nbsp;Stanley M. Lemon ,&nbsp;Yanming Du ,&nbsp;You Li","doi":"10.1016/j.antiviral.2025.106145","DOIUrl":"10.1016/j.antiviral.2025.106145","url":null,"abstract":"<div><div>Despite the considerable clinical and economic burden imposed by hepatitis A virus (HAV) infection, both globally and in U.S., there are currently no available antiviral therapies for the treatment of type A hepatitis. Here we describe novel third-generation hepato-selective dihydroquinolizinones (HS-DHQs) with cellular uptake mediated by transport via hepatocyte-specific solute organic anion transporter family members 1B1 and 1B3 (OATP1B1-B3). The lead HS-DHQ compound, HS83128, demonstrates robust inhibition of the host cell TENT4A/B terminal nucleotidyltransferases required for efficient HAV RNA synthesis (IC₅₀ 6–25nM), and potent antiviral activity against HAV in cell culture (EC₅₀ 0.6 nM). Pharmacokinetic studies in CD-1 mice receiving comparable oral doses of HS83128 and a first-generation dihydroquinolizinone, RG7834, revealed a 5-fold increase in intrahepatic drug concentration and more than 10-fold improvement in liver versus nervous system tissue selectivity. Twice-daily oral administration of HS83128 rapidly arrested viral replication in HAV-infected <em>Ifnar1</em>^{<em>−/−</em>} mice, reducing fecal virus shedding and cytokine markers of hepatic inflammation and reversing virus-induced liver injury. The hepato-selective nature of HS83128 may reduce the risk of neurologic and reproductive track toxicities observed with long-term administration of other dihydroquinolizinones, making it a candidate for the first antiviral therapy of hepatitis A.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106145"},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673353","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":"The fusion peptide of the spike protein S2 domain may be a mimetic analog of β-coronaviruses and serve as a novel virus-host membrane fusion inhibitor","authors":"Abass Alao Safiriyu ,&nbsp;Afaq Hussain ,&nbsp;Nikesh Dewangan ,&nbsp;Grishma Kasle ,&nbsp;Kenneth Shindler ,&nbsp;Debnath Pal ,&nbsp;Jayasri Das Sarma","doi":"10.1016/j.antiviral.2025.106144","DOIUrl":"10.1016/j.antiviral.2025.106144","url":null,"abstract":"<div><div>Coronavirus has garnered more attention recently, particularly in the aftermath of the 2019 pandemic. The β genus of the coronavirus family has demonstrated a significant threat to humanity. Current mitigation strategies involve the development of vaccines and repurposing drugs for symptomatic management of coronavirus infection, specifically SARS-Cov 2. Fusion inhibitors that are available as antiviral drugs for coronavirus have targeted the heptad repeat (HR) 1 and 2 in the S2 domain of the spike protein. The current study identified a fusion peptide (FP) upstream of HR1 as a potential target for developing membrane fusion inhibitors, and mimetic peptides analogous to the FP segment were tested for antiviral activity. Four mimetic fusion peptides (MFPs) (RSA59PP (MFP633), RSA59P (MFP634), RSMHV2P (MFP635), and RSMHV2PP (MFP636)) that are analogous to the FP of murine β coronavirus mouse hepatitis virus (MHV), MHV-A59/RSA59 (PP) and MHV-2/RSMHV2 (P) with central proline mutations, were tested. Results show the ability of MFPs to reduce cell-to-cell fusion and viral replication <em>in vitro</em>. MFP633, which contains a central double proline, exhibited the most potent inhibitory effect in spike protein-mediated membrane fusion assays. Biophysical experiments also demonstrated the strongest interactions between double-proline containing MFPs (MFP633 and MFP636) with biomimetic liposomes. <em>In vivo</em> studies using a liposome-mediated delivery system in mice confirmed the antiviral activity of MFP633. These findings suggest that targeting FPs could develop effective fusion inhibitors against coronaviruses. MFPs act on the host cell membrane by competing with the viral FP during the early stage of host-viral membrane fusion events. MFP633 is a promising peptide drug candidate that warrants future examination to assess whether this and other dual-proline containing peptides may exert similar anti-viral effects in other coronaviruses with conserved FP structures.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106144"},"PeriodicalIF":4.5,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656107","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 hepatitis B virus-free cccDNA-producing stable cell for antiviral screening","authors":"Chengqian Feng ,&nbsp;Jingrong Shi ,&nbsp;Yunfu Chen ,&nbsp;Sisi Chen ,&nbsp;Jianping Cui ,&nbsp;Jun Zhang ,&nbsp;Xiaowen Zheng ,&nbsp;Yaping Wang ,&nbsp;Feng Li","doi":"10.1016/j.antiviral.2025.106143","DOIUrl":"10.1016/j.antiviral.2025.106143","url":null,"abstract":"<div><div>The covalently closed circular DNA (cccDNA) of the Hepatitis B virus (HBV) serves as a template for producing progeny viruses in virally infected hepatocytes. Promising cccDNA-targeting antiviral agents remain unavailable and unpredictable in the research and development pipelines, making sterile HBV elimination challenging at the current stage. The major challenge of discriminating trace amounts of cccDNA from the abundant HBV relaxed circular DNA (rcDNA), which is nearly identical to cccDNA in sequence, substantially discourages efforts to discover and directly screen cccDNA-targeting drugs. Therefore, an easy cccDNA cell culture system is required for high-throughput drug screening. In this study, we designed an HBV cccDNA self-generating stable cell culture system using a functional complementary concept and successfully generated an HBV cccDNA Gaussia luciferase reporter cell line in HepG2 and Huh7 cells. This design ensures that the Gluc signal is exclusively expressed upon cccDNA formation, allowing for the accurate and easy measurement of cccDNA levels via luminescent signals. Using this system, in conjunction with a firefly luciferase reporter to monitor cell activity, we screened 2074 drugs in the HepG2-HBV-cccDNA/Firefly cell line. Four compounds were selected for further experimentation and their anti-HBV effects were confirmed. Thus, this virus-free hepatitis B cccDNA cell culture system provides a valuable and convenient platform for the high-throughput screening of anti-HBV drugs.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106143"},"PeriodicalIF":4.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639450","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":"Host RNA-binding proteins and specialized viral RNA translation mechanisms: Potential antiviral targets","authors":"Leandro Fernández-García ,&nbsp;Mariano A. Garcia-Blanco","doi":"10.1016/j.antiviral.2025.106142","DOIUrl":"10.1016/j.antiviral.2025.106142","url":null,"abstract":"<div><div>RNA-binding proteins (RBPs) are the key regulators of the metabolism of RNA, from its genesis to its degradation. Qualitative and quantitative alterations of RBPs, including their post-translational modifications, impact cellular physiology and are associated with disease processes. Many cellular RBPs also play essential roles in the replication of viruses, especially RNA viruses, which, as obligatory parasites, rely on the host cell's biosynthetic and structural machinery. Viral protein synthesis is a key step in viral lifecycles and critically depends on host RBPs. In many cases, the translation of viral mRNAs employs specialized mechanisms that give viral mRNAs advantages over cellular RNAs. Host RBPs regulate these specialized mechanisms. In this work, we review the role of RBPs in specialized viral RNA translation, focusing on these RBPs as potential antiviral drug targets.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106142"},"PeriodicalIF":4.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633326","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":"Kaempferide enhances type I interferon signaling as a novel broad-spectrum antiviral agent","authors":"Ruikun Du ,&nbsp;Jiawen Sun ,&nbsp;Chunlei Zhang ,&nbsp;Chenglong Chen ,&nbsp;Zinuo Chen ,&nbsp;Varada Anirudhan ,&nbsp;Qinghua Cui ,&nbsp;Hualin Wang ,&nbsp;Lijun Rong ,&nbsp;Yun-Jia Ning","doi":"10.1016/j.antiviral.2025.106141","DOIUrl":"10.1016/j.antiviral.2025.106141","url":null,"abstract":"<div><div>Broad-spectrum antivirals (BSAs) possess unique advantages of being effective against a wide range of both existing and unpredictable emerging viral infections. The host type I interferon (IFN) response serves as a universal defense against diverse viral infections nonspecifically, providing attractive targets to develop novel BSAs. In this study, we identified the flavonoid kaempferide as an enhancer of the type I IFN activated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, promoting the expression of IFN stimulated genes (ISGs) and the establishment of cellular antiviral status. Additionally, our study clearly demonstrated that kaempferide exhibits potent BSA activity against diverse viruses including the highly pathogenic severe fever with thrombocytopenia syndrome virus (SFTSV) and Crimean-Congo hemorrhagic fever virus (CCHFV), by synergizing with either endogenous or exogenous IFNs. Mechanistic study further revealed that kaempferide acts by preventing the suppressor of cytokine signaling 3-mediated negative feedback, prolonging the duration of type I IFN stimulated JAK/STAT signaling. In summary, we herein report kaempferide as a novel potential BSA agent that deserves further development in the future.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106141"},"PeriodicalIF":4.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609995","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":"Curcumin dispersed with colloidal nano-particles inhibits enteric viruses replication","authors":"Maciej Przybylski ,&nbsp;Magdalena Guzowska ,&nbsp;Olga Gazi ,&nbsp;Jakub Urbański ,&nbsp;Pawel Bieganowski","doi":"10.1016/j.antiviral.2025.106140","DOIUrl":"10.1016/j.antiviral.2025.106140","url":null,"abstract":"<div><div>Acute gastroenteritis remains one of the most common health problems despite the progress in prevention and vaccination. The options for viral diarrhea therapy are limited and there is the need for effective treatment. Recently a novel form of the nano-dispersed curcumin that is highly bioavailable was described. This form of curcumin was well tolerated by the cells in culture and was rapidly absorbed into the blood plasma after oral administration. We tested the antiviral activity of this curcumin formulation <em>in vitro</em> using several viruses associated with gastrointestinal infections, like astrovirus, norovirus rotavirus, adenovirus, echovirus, and coxackievirus. We did observe strong replication inhibition of all tested viruses. These results suggest that the tested form of curcumin is a promising candidate for a broad-spectrum antiviral drug.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106140"},"PeriodicalIF":4.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584492","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":"CVA16 infection causes neurological injury by engaging TLR2/MYD88/TNF-α/CXCL1 signalling pathway in hSCARB2 knock-in mice","authors":"Yu Wang ,&nbsp;Yong Wu ,&nbsp;Yuya Wang ,&nbsp;Rui Xiong ,&nbsp;Chen Ling ,&nbsp;Yuan Cao ,&nbsp;Yining Wang ,&nbsp;Yanwei Yang ,&nbsp;Zhe Qu ,&nbsp;Nan Xu ,&nbsp;Susu Liu ,&nbsp;Weijia Li ,&nbsp;Zhe Lv ,&nbsp;Zhongyu Hu ,&nbsp;Changfa Fan","doi":"10.1016/j.antiviral.2025.106133","DOIUrl":"10.1016/j.antiviral.2025.106133","url":null,"abstract":"<div><div><em>Coxsackievirus</em> A16 (CVA16), a major pathogen responsible for hand-foot-and-mouth disease (HFMD) in children, has frequently replaced <em>Enterovirus</em> A71 as the predominant causative agent in China and other Asia-Pacific regions. The lack effective drugs and vaccines against this virus exacerbates the concerns on its outbreaks. Clinical reports and laboratory studies indicate that CVA16 infection may lead to neurological injury, but the precise mechanisms remain elusive. In this study, we meticulously established a CVA16 murine disease model using 3-week-old hSCARB2 knock-in mice through intracranial inoculation. Within 4–7 days post-infection, the infected mice exhibited severe neurological symptoms featured as limb paralysis, hind limb weakness and ataxia. Furthermore, high viral loads were detected in the brain, spleen, skeletal muscle tissues, indicating a systemic infection. A robust cytokine response was observed, characterized with the elevation of TNF-α, IL-12 (p40), IL-10 and MIP-1β. Histological and immunofluorescence staining revealed extensive inflammation, marked by the concentrated infiltration of astrocytes cells, as well as severe neurological injury, which included hypertrophic and extended pseudopodia microglia, increased astrocytes with long and stretched protuberances, markedly decreased neuronal cell bodies and nerve fibers in brain. No visible pathological changes were observed in spinal cord tissues. RNA sequencing and immunofluorescence staining of brain tissue verification assays indicated that the neurological injury may engage in TLR2/MYD88/TNF-α/CXCL1 signal pathway. Over all, this work addressed the gap in the availability of CVA16 disease rodent model for vaccine development and provided novel insights into the mechanisms underlying neurological injury caused by <em>enteroviruses</em> and other neurotropic viruses.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106133"},"PeriodicalIF":4.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584494","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}

{"title":"Bemnifosbuvir and ruzasvir in combination exhibit potent synergistic antiviral activity in vitro while maintaining a favorable nonclinical safety profile in vivo","authors":"Steven S. Good,&nbsp;Shouqi Luo ,&nbsp;Kai Lin ,&nbsp;Alex Vo,&nbsp;Nancy G.B. Agrawal,&nbsp;Jean-Pierre Sommadossi","doi":"10.1016/j.antiviral.2025.106137","DOIUrl":"10.1016/j.antiviral.2025.106137","url":null,"abstract":"<div><div>Bemnifosbuvir (BEM), the orally available hemisulfate salt of the double prodrug of a guanosine nucleotide analog, is a potent, selective, and pan-genotypic inhibitor of HCV nonstructural protein 5B, an RNA-dependent RNA polymerase necessary for viral replication. Similarly, ruzasvir (RZR) is an orally available, highly potent, selective, and pan-genotypic inhibitor of HCV nonstructural protein 5A, an essential component of the viral replication complex. The antiviral effects of the combination of these two complementary direct-acting antivirals were determined in HCV GT1b Huh-7 replicon cells. Two independent <em>in vitro</em> evaluations suggested that BEM and RZR act synergistically to inhibit HCV replication without accompanying cytotoxicity. Additionally, the toxicity and toxicokinetic properties of BEM and RZR administered individually or in combination were investigated in rats given daily oral doses at 500 mg/kg of each drug for 13 weeks, with an interim analysis at 4 weeks. All doses were well tolerated with no test article-related adverse effects identified in either the separate or combined dose groups. Moreover, toxicokinetic analyses conducted on dose days 1, 28 and 84 indicated minimal pharmacokinetic interactions between the two drugs in rats, with AUC values for AT-511 (free base form of BEM), its major circulating metabolites, and RZR being similar, regardless of separate or co-administration.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106137"},"PeriodicalIF":4.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584490","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}