Antiviral research最新文献

{"title":"Tenofovir alafenamide promotes weight gain and impairs fatty acid metabolism-related signaling pathways in visceral fat tissue compared to tenofovir disoproxil fumarate","authors":"Bryan Dulion ,&nbsp;Arnold Z. Olali ,&nbsp;Niyati Patel ,&nbsp;Amber K. Virdi ,&nbsp;Ankur Naqib ,&nbsp;Jennillee Wallace ,&nbsp;Ryan D. Ross","doi":"10.1016/j.antiviral.2025.106151","DOIUrl":"10.1016/j.antiviral.2025.106151","url":null,"abstract":"<div><div>Modern antiretroviral therapy (ART) is associated with rapid weight gain, which appears to be antiretroviral-specific. Tenofovir is a nucleoside reverse transcriptase inhibitor commonly employed as a backbone in many ART formulations. Tenofovir alafenamide (TAF) has been associated with significant weight gain in people living with HIV (PLWH) initiating ART. Interestingly, tenofovir disoproxil fumarate (TDF), has no impact on weight or may even be weight suppressive. The current study compared the impact of two tenofovir-based ART formulations on weight and adipose tissue. We utilized a humanized mouse model of HIV-infection and administered two clinically relevant ART combinations TAF/dolutegravir (DTG)/emtricitabine (FTC) and TDF/DTG/FTC. As expected, female mice treated with TAF/DTG/FTC had the greatest weight gain and fat accumulation, as measured by dual energy x-ray absorptiometry (DXA). As ART-induced accumulation of visceral adipose tissue is linked to mortality, we isolated visceral adipose tissue for targeted (qPCR) and non-targeted (RNAseq) gene expression. Mice treated with TAF/DTG/FTC had increased expression of adipocyte differentiation related genes, leptin and PPAR-γ. RNAseq revealed that while the expression patterns for both TAF/DTG/FTC and TDF/DTG/FTC treated mice were similar, there were key differences. Specifically, KEGG pathway analysis indicated that TAF/DTG/FTC treated mice showed suppression of multiple fatty acid metabolism related pathways, while TDF/DTG/FTC treated mice showed evidence for increased thermogenesis. The results suggest that weight gain associated with TAF-based ART may be due to impaired adipocyte mediated lipid handling, while suppressed weight gain with TDF-based ART may be secondary to increased browning of visceral adipocytes, although independent validation is necessary.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106151"},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735272","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":"Inhibition of influenza A virus proliferation in mice via universal RNA interference","authors":"Yu-Shen Kuo ,&nbsp;Pei-Chuan Chiang ,&nbsp;Chieh-Ying Kuo ,&nbsp;Chung-Guei Huang ,&nbsp;Ming-Ling Kuo ,&nbsp;Ya-Fang Chiu","doi":"10.1016/j.antiviral.2025.106149","DOIUrl":"10.1016/j.antiviral.2025.106149","url":null,"abstract":"<div><div>Influenza A virus (IAV) is a respiratory pathogen that causes seasonal outbreaks and periodic pandemics. As frequent mutations in the IAV viral genome often render vaccines ineffective or inefficient in preventing the latest outbreak, there is a need to explore other preventive strategies to control the disease. This study sought to investigate the use of antiviral short hairpin RNA (shRNA), delivered by a recombinant adeno-associated virus (AAV), for the prevention of IAV infections. Conserved regions with less than 10 % of variation were identified from IAV genome sequences deposited in the National Center for Biotechnology Information (NCBI) database between 2000 and 2023. The shRNA targeting these conserved sequences was transcribed from the human RNA polymerase III U6 promoter in an AAV system. This study demonstrates that AAV delivery of shRNA against IAV genes encoding two of the viral RNA-dependent RNA polymerase subunits, PB1 and PB2, inhibits the replication of IAV H1N1 and H3N2 viruses in Madin-Darby canine kidney (MDCK) cells. Delivery of shPB1 to lung tissue in mice through AAV also provided effective protection against IAV infection. These results offer support for a shRNA-based strategy of influenza prevention.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"238 ","pages":"Article 106149"},"PeriodicalIF":4.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727520","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":"α-Glucosidase inhibitors as broad-spectrum antivirals: Current knowledge and future prospects","authors":"James WJ. Kang ,&nbsp;Kitti Wing Ki Chan ,&nbsp;Subhash G. Vasudevan ,&nbsp;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":"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":"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":"Host-targeted repurposed diltiazem enhances the antiviral activity of direct acting antivirals against Influenza A virus and SARS-CoV-2","authors":"Blandine Padey ,&nbsp;Clément Droillard ,&nbsp;Victoria Dulière ,&nbsp;Julien Fouret ,&nbsp;Claire Nicolas de Lamballerie ,&nbsp;Cédrine Milesi ,&nbsp;Emilie Laurent ,&nbsp;Pauline Brun ,&nbsp;Aurélien Traversier ,&nbsp;Thomas Julien ,&nbsp;Olivier Terrier ,&nbsp;Manuel Rosa-Calatrava ,&nbsp;Andrés Pizzorno","doi":"10.1016/j.antiviral.2025.106138","DOIUrl":"10.1016/j.antiviral.2025.106138","url":null,"abstract":"<div><div>Viral respiratory infections remain a major and recurrent public health threat. Among them, influenza viruses are responsible for ⁓500,000 deaths worldwide and a high economic burden. The recurrent threat of emerging zoonotic or pandemic viruses worsens this scenario, being SARS-CoV-2 and the millions of COVID-19 deaths the most recent example. The rapid evolution of circulating influenza and SARS-CoV-2 viruses allows the emergence and dissemination of variant strains carrying mutations resulting in suboptimal vaccine protection and/or reduced efficacy of current limited therapeutic arsenal. In this context, host-targeted approaches constitute a promising antiviral strategy aiming to achieve broad-spectrum activity and mitigate the emergence of viral resistance against classic direct acting antivirals. Here, we demonstrated that diltiazem, a calcium channel blocker currently used to treat angor, induces an ISG expression profile characteristic of an antiviral cellular state mainly driven by IFN-λ. We then evaluated the potential of the diltiazem-baloxavir combination against Influenza A wild-type and the PA I38T resistant strain in cell culture and human airway epithelia (HAE). We analogously evaluated the diltiazem-molnupiravir combination against SARS-CoV-2, including variants of concern. Our results demonstrate the broad-spectrum antiviral activity of diltiazem against Influenza A viruses, including resistant strains, as well as the capacity to potentiate the antiviral effect of baloxavir. The diltiazem-molnupiravir combination further reduced viral production and protected the integrity of HAE infected with SARS-CoV-2. This study highlights the major interest of combining direct acting and host-targeted agents as a promising strategy against circulating and emerging viruses.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"237 ","pages":"Article 106138"},"PeriodicalIF":4.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571926","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}