Antiviral research最新文献

{"title":"Meeting Report: 39th International Conference on Antiviral Research in Prague, Czech Republic, April 27-May 1, 2026.","authors":"Robert Jordan, Nancie M Archin, Wendy Barclay, Andrea Brancale, Valeria Cagno, Rhonda Cardin, Kara Carter, Leen Delang, Joana Rocha-Pereira, Joy Y Feng, Brian Gentry, Lara J Herrero, Branka Horvat, Zlatko Janeba, Radim Nenka, Justin Julander, Jenny G Low, Daniel Ruzek, Luis M Schang, Katherine L Seley-Radtke, Timothy P Sheahan, Jessica R Spengler, John E Tavis, Viet Loan Dao Thi, Jan Weber, Stephen R Welch, David Durantel","doi":"10.1016/j.antiviral.2026.106549","DOIUrl":"https://doi.org/10.1016/j.antiviral.2026.106549","url":null,"abstract":"<p><p>The 39^th International Conference on Antiviral Research (ICAR), hosted by the International Society for Antiviral Research (ISAR), took place April 27-May 1, 2026, at the Cubex Centrum Praha in Prague, Czech Republic. The annual meeting brought together scientists from academia, industry, government, and public health to present recent advances across antiviral discovery, therapeutic development, vaccine research, host-directed approaches, and preparedness for emerging and re-emerging viral threats. The 2026 program included plenary and award lectures, oral presentations, poster sessions, late-breaking presentations, shotgun presentations, and focused scientific sessions spanning arboviruses, coronaviruses, influenza, respiratory syncytial virus (RSV), chronic, latent, and persistent viruses, hepatotropic and gastrointestinal viruses, artificial intelligence (AI)-driven drug discovery, broad-spectrum antiviral drugs, non-respiratory biothreat viruses, and pandemic preparedness. The opening plenary featured lectures on influenza virus and hepatitis D virus entry inhibition, while ISAR award lectures highlighted major contributions to antiviral science, including global virus research, antiviral and vaccine development, broad-spectrum antiviral approaches, rational drug design, and small-molecule development for yellow fever disease. ICAR 2026 also included dedicated activities to support professional development and community building, including the Women in Science Roundtable, First Timer and New Member Morning Coffee, PechaKucha Competition, the Chu Family Foundation Fellowship presentations, ISAR Annual Meeting, and Career Development Interactive Roundtable. Overall, ICAR 2026 reinforced ISAR's role as an international forum for scientific exchange, interdisciplinary collaboration, and development of the next generation of antiviral researchers.</p>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":" ","pages":"106549"},"PeriodicalIF":4.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179212","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":"Nucleoside analogs containing an imino-ribitol sugar exhibit a distinctive pattern of interference with RNA synthesis by the Dengue virus polymerase.","authors":"Sandesh Deshpande, Anthony J B van Hameren, James M Wood, Rinu Shrestha, Kevin Sparrow, Gary B Evans, Lawrence D Harris, Esther M M Bulloch, Richard L Kingston","doi":"10.1016/j.antiviral.2026.106541","DOIUrl":"10.1016/j.antiviral.2026.106541","url":null,"abstract":"<p><p>Iminovirs are antiviral nucleoside analogs in which the naturally occurring ribose sugar is replaced by an imino-ribitol group, linked to the base by a non-native carbon-carbon bond. The prototypical iminovir is galidesivir, an adenosine analog that inhibits replication of a wide range of RNA viruses. Initial investigation of the effects of galidesivir triphosphate on RNA synthesis by the Dengue virus serotype 2 (DENV-2) polymerase showed that the analog was incorporated with reduced efficiency relative to ATP, and incorporation of the analog at consecutive sites in the nascent RNA was effectively blocked. To better understand the origin of these effects, we have extended this work, studying both galidesivir triphosphate and three closely related compounds with variations in both the base and sugar groups. We investigated the effects of these compounds on RNA synthesis using primer extension assays with varying template sequences. Quantitative analysis of the data confirms that the DENV-2 polymerase processes iminovir triphosphates less efficiently than ATP. Galidesivir, for example, is incorporated into the nascent RNA chain around thirteen times slower than adenosine, a difference that is fully ascribable to the presence of the imino-ribitol group. Furthermore, consecutive incorporation of iminovirs is strongly disfavored. Consequently, iminovir triphosphates slow the overall rate of RNA chain extension when present at high concentrations, with this effect modulated by the template sequence. However, iminovir incorporation into the nascent RNA strand does not act to terminate RNA synthesis, which suggests that antiviral activity must result from events downstream of initial incorporation.</p>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":" ","pages":"106541"},"PeriodicalIF":4.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179123","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":"RNA-Dependent RNA Polymerase (RdRp): Structure, Function, and Antiviral Targeting in RNA Viruses.","authors":"Wei Liu, Yiyi Feng, Fanxin Liu, Chan Ding, Xusheng Qiu, Jun Dai","doi":"10.1016/j.antiviral.2026.106544","DOIUrl":"https://doi.org/10.1016/j.antiviral.2026.106544","url":null,"abstract":"<p><p>RNA-dependent RNA polymerase (RdRp) is the core catalytic enzyme that mediates RNA viral replication and transcription. The polymerase facilitates template and substrate channel assembly, nucleotide selectivity, and phosphodiester bond formation, making it an essential component of the viral life cycle. RdRps differ greatly in domain organization and replication initiation mechanisms across viruses, but their catalytic cores are highly conserved. The intrinsic low-fidelity replication of RdRp accelerates viral evolution, while some viruses fine-tune replication fidelity by proofreading exonucleases or accessory proteins that balance genome stability and adaptive variation. Given its conserved structure and non-redundant function, RdRp is a key target for broad-spectrum antiviral development, and numerous nucleoside (NIs) and non-nucleoside inhibitors (NNIs) are currently undergoing clinical or preclinical evaluation. However, three major obstacles limit inhibitor development: mutation-induced drug resistance, structural RdRp heterogeneity across viral species, and unfavorable pharmacokinetic properties. This review summarizes the structural basis and catalytic mechanisms of RdRp, discusses its functions during viral replication, genetic variation and virus-host interactions, and updates NI/NNI design, mechanisms, and development. We also dissect drug resistance mechanisms and inhibitor optimization strategies using advanced high-resolution structural and functional analyses. Overall, we provide insights for the rational development of broad-spectrum, potent antiviral agents with a low risk of RdRp resistance.</p>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":" ","pages":"106544"},"PeriodicalIF":4.3,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179144","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":"Corrigendum to \"Construction of a suckling mouse model based on an EV-C96 clinical isolate and its application in drug screening and vaccine development\" [Antivir. Res. 254 (2026) 106511].","authors":"Jing Wang, Ying Qu, Yunyi He, Qiu Yang, Hanyu Zhu, Yongbei Chen, Xianlong Duan, Huanying Zheng, Shengjun Xiao, Qiliang Liu, Hongbo Liu","doi":"10.1016/j.antiviral.2026.106543","DOIUrl":"https://doi.org/10.1016/j.antiviral.2026.106543","url":null,"abstract":"","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":" ","pages":"106543"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103408","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":"Overview of gene editing strategies against HBV","authors":"Zak T. Janetzki ,&nbsp;Laura C. McCoullough ,&nbsp;Peter A. Revill ,&nbsp;Margaret Littlejohn","doi":"10.1016/j.antiviral.2026.106355","DOIUrl":"10.1016/j.antiviral.2026.106355","url":null,"abstract":"<div><div>254 million people currently live with chronic hepatitis B virus (HBV) infection, with over 1 million deaths annually due to complications such as cirrhosis and hepatocellular carcinoma. Although current direct-acting antivirals suppress HBV replication, they do not eliminate the virus and rarely lead to HBV functional cure, defined as the loss of serum hepatitis B surface antigen (HBsAg) and DNA. A major barrier to achieving HBV functional cure is the HBV covalently closed circular DNA minichromosome (cccDNA), which hides from the immune system in the nucleus of an infected cell, and is very stable. Another barrier is integration of incomplete HBV genomes into the host genome, which is the main source of HBsAg in later disease stages, and is difficult to target without impacting the human genome. New direct-acting antivirals are required that target different stages of the HBV replication cycle, including the HBV cccDNA and integrated DNA to improve rates of functional cure. The development of gene editing tools provides an opportunity to develop novel therapies that target the HBV cccDNA, integrated DNA and HBV RNA. This review explores the different gene editing tools that have been used to target the HBV cccDNA, integrated DNA and RNA.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106355"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028384","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 UL23 thymidine kinase of Marek's disease virus is a target for anti-HSV drug development","authors":"Yunzhe Kang ,&nbsp;Rui Wang ,&nbsp;Lulu Yao ,&nbsp;Xiuwen Yang ,&nbsp;Wenhui Zhu ,&nbsp;Lele Wang ,&nbsp;Gaiping Zhang ,&nbsp;Guoqing Zhuang ,&nbsp;Aijun Sun","doi":"10.1016/j.antiviral.2026.106344","DOIUrl":"10.1016/j.antiviral.2026.106344","url":null,"abstract":"<div><div>Marek's disease virus (MDV) is an oncogenic alphaherpesvirus causing rapid onset of malignant T-cell lymphomas in chickens. <em>UL23</em>-encoded thymidine kinase (TK) has highly conserved sequences in distinctive alphaherpesviruses. However, its enzymatic activity in viral replication and pathogenesis is poorly understood. Here, we found that the nucleotide-binding sites and the functional domains related to activity of TK from different alphaherpesviruses are strongly conserved. We show that an MDV-1 <em>UL23</em>-null mutation (Md5BACΔ<em>UL23</em>) significantly reduces MDV replication <em>in vitro</em> and <em>in vivo</em>. Interestingly, chimeric viruses with replacement of MDV-1 <em>UL23</em> with MDV-2, HVT, PRV, or HSV-1 <em>UL23</em> showed partial recovery of MDV replication and pathogenicity. In addition, Md5BACΔ<em>UL23</em> infection resulted in higher survival rate and lower MDV-specific tumor incidence, which could be partially compensated by chimeric viruses. The replication properties of <em>UL23</em> chimeric alphaherpesviruses are susceptible to acyclovir inhibition, whereas Md5BACΔ<em>UL23</em> exhibits complete resistance. Overall, our establishment of the MDV-TK chimeric model provides a robust basis for evaluating TK-targeted therapeutics, accelerating clinical translation of novel anti-herpesvirus strategies.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106344"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987929","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":"Targeted organic acid profiling in Crimean-Congo hemorrhagic fever: A metabolomics-based approach to biomarker discovery","authors":"Halef Okan Doğan ,&nbsp;Seyit Ali Büyüktuna ,&nbsp;Gözde Ertürk Zararsız ,&nbsp;Serra İlayda Yerlitaş ,&nbsp;Ahu Cephe ,&nbsp;Ahmet Turan Koç ,&nbsp;Rıdvan Karaarslan ,&nbsp;Zülal Peri Yoldaş Aslanoğlu ,&nbsp;Merve Gülşah Lafçı ,&nbsp;Meltem Kurt Yenihan ,&nbsp;Alperen Aydemir ,&nbsp;Ebrar Büşra Yıldırım ,&nbsp;Gökmen Zararsız","doi":"10.1016/j.antiviral.2026.106358","DOIUrl":"10.1016/j.antiviral.2026.106358","url":null,"abstract":"<div><div>Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne viral infection associated with high morbidity and mortality. Understanding the metabolic alterations associated with the disease may uncover novel biomarkers for diagnosis and disease severity assessment. In this study, we conducted a targeted metabolomic analysis using LC-MS/MS to quantify serum organic acid levels in 115 CCHF-positive patients, 30 CCHF-negative patients, and 45 healthy controls. This is the first study to comprehensively profile organic acid alterations in CCHFV using targeted metabolomics. Our findings revealed that several organic acids, notably alpha-ketoglutaric acid, malic acid, p-hydroxyphenyllactic acid, and 3-hydroxyisobutyric acid, were significantly elevated in CCHFV patients and positively correlated with markers of inflammation and coagulation. These metabolites demonstrated strong prognostic performance for intensive care unit (ICU) admission. Additionally, survival analysis indicated that elevated levels of specific organic acids were associated with increased mortality risk. Pathway enrichment analysis identified dysregulation of the TCA cycle, pyruvate metabolism, and amino acid pathways in CCHF patients. Our results suggest that specific organic acids may serve as novel biomarkers for disease severity and prognosis, offering potential tools for early risk stratification and improved clinical management of CCHF.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106358"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099605","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":"Therapeutic intranasal delivery of NanoSTING provides broad protection against seasonal and highly pathogenic influenza strains","authors":"Ankita Leekha ,&nbsp;Kate Reichel ,&nbsp;Brett Hurst ,&nbsp;Navin Varadarajan","doi":"10.1016/j.antiviral.2026.106342","DOIUrl":"10.1016/j.antiviral.2026.106342","url":null,"abstract":"<div><div>Influenza is a major global threat due to several factors, including great zoonotic potential, ongoing antigenic drift, limited effectiveness of current vaccines, and the emergence of drug-resistant viral strains. Broad-spectrum therapeutic regimens that can treat vulnerable populations, enable faster resolution of symptoms, and decrease fatality rates are a long-sought objective for influenza. Here, we report the development of NanoSTING, a liposomally encapsulated STING agonist (cGAMP), as a single-dose intranasal treatment of influenza. We demonstrate that NanoSTING is stable under simple refrigeration conditions, with no loss of encapsulated cGAMP, for up to a year. A single dose of NanoSTING administered intranasally induced robust type I interferon responses in the nasal and lung tissue of mice without observable toxicity. In mouse challenge models of influenza A (H1N1 or highly pathogenic H5N1) and influenza B, NanoSTING provided therapeutic protection at least as effective as ten doses of oseltamivir. NanoSTING demonstrated therapeutic efficacy even when administered 48–72 h post-infection. Furthermore, NanoSTING maintained its activity in aged and immunocompromised mice, as evidenced by the robust induction of interferon responses in nasal tissues, highlighting its potential for use in vulnerable individuals. These attributes of NanoSTING support its potential use as a promising host-directed anti-viral with a large therapeutic window and broad-spectrum efficacy.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106342"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987548","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":"Lapachol, a dihydroorotate dehydrogenase inhibitor, demonstrates antiviral activity against feline calicivirus in vitro and in vivo","authors":"Zexin Liu ,&nbsp;Guohong Wu ,&nbsp;Jianwei Mao ,&nbsp;Yutong Zheng ,&nbsp;Qizhen Fu ,&nbsp;Sifan Lin ,&nbsp;Yizhou Chen ,&nbsp;Weisan Chen ,&nbsp;Pei Zhou ,&nbsp;Jianxin Chen","doi":"10.1016/j.antiviral.2026.106354","DOIUrl":"10.1016/j.antiviral.2026.106354","url":null,"abstract":"<div><div>Feline calicivirus (FCV) infection poses a significant threat to domestic cats, causing a spectrum of clinical symptoms ranging from mild respiratory issues to severe systemic diseases. Although FCV vaccines are available, their protective efficacy is limited by the extensive genetic diversity and antigenic variability of FCV. To date, no approved antiviral drug is available, highlighting the urgent need for effective therapeutics. Here, we screened a library of 431 small-molecule compounds to identify novel antiviral agents against FCV, leading to the discovery of ten new inhibitors, including five naphthoquinones. Among these, lapachol demonstrated the most potent anti-FCV activity, with a half-maximal effective concentration (EC₅₀) of 1.87 μM and a selectivity index (SI) of 677. Mechanistic studies revealed that lapachol exerts its antiviral effects by inhibiting feline dihydroorotate dehydrogenase (DHODH), thereby disrupting the synthesis of pyrimidine nucleotides, which are essential for viral replication. Further investigations showed that silencing DHODH enhanced lapachol's antiviral activity, while supplementation with pyrimidine nucleotides or DHODH overexpression reversed its effects. Importantly, oral administration of lapachol at 5 mg/kg significantly reduced virus shedding from the oral and nasal cavities in FCV-infected cats, promoted recovery from weight loss, and alleviated oral ulceration and pulmonary lesions, without inducing observable hepatic or renal toxicity. These findings demonstrate that lapachol is a promising candidate for the treatment of FCV infections, and underscore the potential of DHODH as a viable therapeutic target for antiviral drug development.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106354"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040284","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":"Pharmacokinetics and safety of HIV fusion inhibitor Lipovirtide in non-human primates","authors":"Yuanmei Zhu ,&nbsp;Huihui Chong ,&nbsp;Nian Liu,&nbsp;Yuxian He","doi":"10.1016/j.antiviral.2026.106357","DOIUrl":"10.1016/j.antiviral.2026.106357","url":null,"abstract":"<div><div>Lipovirtide, also known as LP-80, is a lipopeptide-based HIV fusion inhibitor with potent broad-spectrum and long-lasting antiviral activity. We recently reported the pharmacokinetics and safety of Lipovirtide in rats (Zhu et al. 2025); herein, its pharmacokinetics and safety profiles in cynomolgus macaques were systematically evaluated. Lipovirtide was rapidly absorbed after subcutaneous administration, with absolute bioavailability (F) of 110.11 % in male and 92.33 % in female. The time to reach maximum plasma concentration (T_max) ranged from 4 to 8 h, and the terminal half-life (T_1/2) was between 10.18 and 13.51 h. Comprehensive safety assessments revealed no significant effects on cardiovascular or respiratory functions in conscious macaques after a single subcutaneous administration. General toxicity studies demonstrated its excellent tolerability, with a maximum tolerated dose above 150 mg/kg for single dosing; the 4-week and 39-week repeated dosing determined the no-observed-adverse-effect level (NOAEL) to be 15 mg/kg. Toxicokinetic analyses confirmed that long-term administration did not lead to drug accumulation in both male and female animals. No anti-drug antibody (ADA) formation was observed throughout the study schedule. Collectively, our preclinical characterizations provide compelling data to support the clinical development of Lipovirtide, which has already progressed to a phase III clinical trial.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"247 ","pages":"Article 106357"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050165","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}