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Engineering a robust infectious clone and gene silencing vector from blackberry yellow vein associated virus. 从黑莓黄脉相关病毒中提取强感染性克隆和基因沉默载体。
IF 2.5 4区 医学
Virus research Pub Date : 2024-11-07 DOI: 10.1016/j.virusres.2024.199488
Andrea Sierra Mejia, Dan E V Villamor, Aaron Rocha, William M Wintermantel, Ioannis E Tzanetakis
{"title":"Engineering a robust infectious clone and gene silencing vector from blackberry yellow vein associated virus.","authors":"Andrea Sierra Mejia, Dan E V Villamor, Aaron Rocha, William M Wintermantel, Ioannis E Tzanetakis","doi":"10.1016/j.virusres.2024.199488","DOIUrl":"10.1016/j.virusres.2024.199488","url":null,"abstract":"<p><p>Criniviruses are emerging pathogens responsible for significant disease outbreaks worldwide. Among them, blackberry yellow vein-associated virus (BYVaV) is prevalent in blackberry-producing areas of the United States and, when present in the blackberry yellow vein disease complex with other viruses, can lead to substantial crop losses. To better understand BYVaV biology and its role in virus complex disease development, we developed a BYVaV-derived infectious clone and a virus-induced gene silencing (VIGS) vector. The infectious clone successfully induced systemic infection and symptom development in Nicotiana benthamiana. Additionally, transmission of the recombinant virus to indicator plants was confirmed using the whitefly vector Trialeurodes vaporariorum. The infectious clone was subsequently modified into a VIGS vector, with the foreign insert remaining stable for the length of the study. This work provides essential tools for advancing the study of BYVaV biology and conducting genomic studies in its natural hosts.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Comprehensive phylogenomic analysis of Zika virus: Insights into its origin, past evolutionary dynamics, and global spread. 寨卡病毒的全面系统发生组分析:洞察寨卡病毒的起源、过去的进化动态和全球传播。
IF 2.5 4区 医学
Virus research Pub Date : 2024-11-07 DOI: 10.1016/j.virusres.2024.199490
Nicola Zadra, Annapaola Rizzoli
{"title":"Comprehensive phylogenomic analysis of Zika virus: Insights into its origin, past evolutionary dynamics, and global spread.","authors":"Nicola Zadra, Annapaola Rizzoli","doi":"10.1016/j.virusres.2024.199490","DOIUrl":"10.1016/j.virusres.2024.199490","url":null,"abstract":"<p><strong>Background: </strong>Zika virus (ZIKV), a Flaviviridae family member, has been linked to severe neurological disorders. Despite detailed studies on recent outbreaks, the early evolutionary history of ZIKV remains partially unclear. This study elucidates ZIKV origin and evolutionary dynamics, focusing on recombination events, early lineage diversification, and virus spread across continents.</p><p><strong>Methods: </strong>We assessed recombination using multiple methods. We conducted Bayesian phylogenetic analyses to understand the evolutionary relationships and timing of key diversification events. Model selection was carried out to determine the most appropriate evolutionary model for our dataset.</p><p><strong>Results: </strong>Our phylogenies revealed recent recombination between Singaporean and African lineages, indicating the co-circulation of diverse lineages during outbreaks. Thailand was identified as a crucial hub in the spread across Asia. The phylogenetic analysis suggests that the ZIKV lineage dates back to the eleventh century, with the first significant diversification occurring in the nineteenth century. The timing of the re-introduction of the Asian lineage into Africa and the delay between probable introduction and outbreak onset were also determined.</p><p><strong>Conclusions: </strong>This study provides novel insights into ZIKV's origin and early evolutionary dynamics, highlighting Thailand's role in the spread of the virus in Asia and recent recombination events between distant lineages. These findings emphasize the need for continuous surveillance and a better understanding of ZIKV biology to forecast and mitigate future outbreaks.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Glucocorticoid receptor and specificity protein 1 (Sp1) or Sp3 transactivate HSV-1 ICP0 promoter sequences but a GC-rich binding antibiotic, Mithramycin A, impairs reactivation from latency 糖皮质激素受体和特异性蛋白 1(Sp1)或 Sp3 可反式激活 HSV-1 ICP0 启动子序列,但一种富含 GC 结合力的抗生素 Mithramycin A 会影响潜伏期的再激活。
IF 2.5 4区 医学
Virus research Pub Date : 2024-11-04 DOI: 10.1016/j.virusres.2024.199487
{"title":"Glucocorticoid receptor and specificity protein 1 (Sp1) or Sp3 transactivate HSV-1 ICP0 promoter sequences but a GC-rich binding antibiotic, Mithramycin A, impairs reactivation from latency","authors":"","doi":"10.1016/j.virusres.2024.199487","DOIUrl":"10.1016/j.virusres.2024.199487","url":null,"abstract":"<div><div>Glucocorticoid receptor (GR) activation enhances Human alpha-herpes virus 1 (HSV-1) replication and explant-induced reactivation from latency. Furthermore, GR and Krüppel-like factor 15 (KLF15) cooperatively transactivate cis-regulatory modules (CRMs) that drive expression of infected cell protein 0 (ICP0), ICP4, and ICP27. KLF and specificity protein (Sp) family members bind GC-rich or C-rich sequences and belong to the same super-family of transcription factors. Based on these observations, we hypothesized CRMs spanning the ICP0 promoter are transactivated by GR and Sp1 or Sp3. CRM-A (-800 to -635), CRM-B (-485 to -635), and CRM-D (-232 to -24), but not CRM-C, were significantly transactivated by GR, DEX, and Sp1 or Sp3 in mouse neuroblastoma cells (Neuro-2A). Mutagenesis of Sp1/Sp3 binding sites were important for transactivation of CRM-A and CRM-B. Chromatin immunoprecipitation studies revealed significantly higher levels of GR occupied ICP0 promoter sequences when Sp1 or Sp3 was over-expressed suggesting these transcriptions factors recruit GR to ICP0 CRM sequences. Mithramycin A, an antibiotic that preferentially binds GC-rich DNA and impairs Sp1/Sp3 dependent transactivation and reduced virus shedding during reactivation from latency in mice latently infected with HSV-1. These studies indicate GR and certain stress-induced cellular transcription factors preferentially bind GC rich DNA, which stimulates HSV-1 gene expression and reactivation from latency in trigeminal ganglia of latently infected mice.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Characterization of Two Lytic Bacteriophages Infecting Carbapenem-Resistant Clinical Klebsiella pneumoniae in Dhaka, Bangladesh. 孟加拉国达卡感染耐碳青霉烯类临床肺炎克雷伯氏菌的两种致死性噬菌体的特征。
IF 2.5 4区 医学
Virus research Pub Date : 2024-11-02 DOI: 10.1016/j.virusres.2024.199491
Nishat Tasnim Ananna, Tushar Ahmed Shishir, Akash Ahmed, Syed Muktadir Al Sium, Md Salman Shakil, Dr Fahim Kabir Monjurul Haque, Md Hasanuzzaman
{"title":"Characterization of Two Lytic Bacteriophages Infecting Carbapenem-Resistant Clinical Klebsiella pneumoniae in Dhaka, Bangladesh.","authors":"Nishat Tasnim Ananna, Tushar Ahmed Shishir, Akash Ahmed, Syed Muktadir Al Sium, Md Salman Shakil, Dr Fahim Kabir Monjurul Haque, Md Hasanuzzaman","doi":"10.1016/j.virusres.2024.199491","DOIUrl":"https://doi.org/10.1016/j.virusres.2024.199491","url":null,"abstract":"<p><p>Bacteriophages or bacteria infecting viruses are genetically diverse. Due to the emergence of antimicrobial-resistant bacteria, lytic bacteriophages are gaining enormous attention for treating superbug infections. Klebsiella pneumoniae is one of the eight most significant nosocomial pathogens and is addressed as a critical priority pathogen by WHO, requiring alternative treatment options. We reported two highly lytic bacteriophages, Klebsiella phage Kpn BM7 and the novel Klebsiella phage Kpn BU9, isolated from hospital wastewater and exhibiting lytic activity against different clinical isolates. Whole-genome analysis revealed that phages BM7 and BU9 belong to class Caudoviricetes. Phage BM7, with a genome length of 170,558 bp, is a member of the genus Marfavirus and the species Marfavirus F48, while phage BU9, with a genome length of 60,450 bp, remains unclassified. Neither phage harbors any lysogenic, toxin, or antimicrobial resistance genes. Both phages can steadily survive up to 40°C and at pH 5-7. The optimal MOI was 0.1 for BM7 and 1 for BU9, with short latent periods of 10 and 25 min and burst sizes of 85 PFU/cell and 12 PFU/cell, respectively. This is the first carbapenem-resistant K. pneumoniae (CRKP) targeting lytic phages to be reported from Bangladesh. This study suggests that BM7 and BU9 are potential candidates for targeting carbapenem-resistant K. pneumoniae.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Exceptional Bluetongue virus (BTV) and Epizootic hemorrhagic disease virus (EHDV) circulation in France in 2023 2023 年法国蓝舌病病毒 (BTV) 和流行性出血病病毒 (EHDV) 的异常流行情况。
IF 2.5 4区 医学
Virus research Pub Date : 2024-11-01 DOI: 10.1016/j.virusres.2024.199489
{"title":"Exceptional Bluetongue virus (BTV) and Epizootic hemorrhagic disease virus (EHDV) circulation in France in 2023","authors":"","doi":"10.1016/j.virusres.2024.199489","DOIUrl":"10.1016/j.virusres.2024.199489","url":null,"abstract":"<div><div>Bluetongue (BT) and Epizootic Hemorrhagic Disease (EHD) are two notifiable animal diseases transmitted to ruminants by small hematophagous midges belonging to the <em>Culicoides</em> genus. The etiological agents, Bluetongue virus (BTV) and Epizootic hemorrhagic disease virus (EHDV), are both members of the <em>Sedoreoviridae</em> family and <em>Orbivirus</em> genus, which include double-stranded (ds) RNA segmented genomes (10 segments). By the end of the summer 2023, first's outbreaks of EHD were reported from the south west of France, concurrently with unexpectedly severe BT cases in Central France and Corsica. Within a few weeks, numerous BT and EHD outbreaks were recorded with significant sanitary and economic impact on cattle and sheep farms (no sanitary impact of EHD for sheep). Using a customized SISPA approach and the nanopore sequencing technology we successfully recovered genomic sequences from viral isolates and blood samples from infected animals from EHD and BT outbreaks. Three different viruses were responsible for these outbreaks: EHDV-8, BTV-8 and BTV-4. The EHDV-8 strain detected in France corresponded to the strain circulating in Tunisia, Sardinia and Spain since 2021 and 2022. A new BTV-8 strain of unknown origin, clearly different from the enzootic strain circulating in France since 2015, was responsible of the BT outbreaks in domestic ruminants in 2023 on both mainland France and Corsica. A second BTV, BTV-4, also involved in BT outbreaks in Corsica, corresponded to a BTV-4 strain occasionally detected on Corsica island since 2016, suggesting either a new introduction of this strain or a silent circulation on the field. The exceptional nature of orbivirus epizootics in France in 2023, including new introduction, emergence or incursions, raises numerous questions regarding BTV and EHDV dynamics and epidemiology and stresses out the need to identify factors involved in these emergences.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Genomic characterization and survey of a second luteovirus infecting blueberries 感染蓝莓的第二种黄体病毒的基因组特征和调查。
IF 2.5 4区 医学
Virus research Pub Date : 2024-10-26 DOI: 10.1016/j.virusres.2024.199480
{"title":"Genomic characterization and survey of a second luteovirus infecting blueberries","authors":"","doi":"10.1016/j.virusres.2024.199480","DOIUrl":"10.1016/j.virusres.2024.199480","url":null,"abstract":"<div><div>New and emerging viral problems may be contributing to blueberry decline. In this research we described a new virus detected in Oregon blueberry production field and surveyed the region for its potential spread. The complete genome sequence of a putative new member of the genus <em>Luteovirus</em> was obtained from blueberry (<em>Vaccinium corymbosum</em> L.) by high throughput sequencing and 5′/3′-RACE. The new virus was tentatively named blueberry virus M (BlVM). Its genome is 5,018 nt long with four putative open reading frames. Similarly to some recently discovered luteoviruses, BlVM does not possess any movement protein (MP). Phylogenetic analysis confirmed clustering of BlVM with the group of non-MP luteoviruses, showing blueberry virus L as the most similar species. Through a small-scale high throughput sequencing survey we obtained 14 additional near complete genomic sequences. A larger survey of 2,654 samples by RT-PCR in Oregon and Washington (USA) found 52 BlVM-positive plants collected from four locations in Oregon. These findings will facilitate monitoring virus distribution and assessment of potential disease associated with this new and emerging blueberry virus.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Signature of viral fossils: a comparative genomics approach to understand the diversity of endogenous retroviruses in bats 病毒化石的特征:了解蝙蝠内源性逆转录病毒多样性的比较基因组学方法。
IF 2.5 4区 医学
Virus research Pub Date : 2024-10-25 DOI: 10.1016/j.virusres.2024.199484
{"title":"Signature of viral fossils: a comparative genomics approach to understand the diversity of endogenous retroviruses in bats","authors":"","doi":"10.1016/j.virusres.2024.199484","DOIUrl":"10.1016/j.virusres.2024.199484","url":null,"abstract":"<div><div>Endogenous retroviruses (ERVs) are traces of past viral infections commonly found in vertebrate genomes. Many ERVs are tightly regulated by the host genomes and co-opted for various functions within the hosts. Bats are the only true volant mammals, with the smallest mammalian genomes and a high fraction of ERVs within the genomes. They are important hosts for various zoonotic viral pathogens and can effectively modulate their immune response to tolerate viral infections. Integrations of retroviruses have been implicated as one of the mechanisms by which bats have co-evolved strategies to combat viral infections. In this study, we investigated the diversity of ERVs in over 40 publicly available bat genomes to understand the distribution and the evolution of ERVs within bats. We observed all classes of ERVs within bat genomes including even the complex lenti retroviruses. Alpha and spuma retroviruses which are generally considered rare in mammals, were common within bats. We observed a positive correlation between bat genome size and length of ERV elements. Interestingly, nearly 30 % of the ERVs within bats are intact suggesting a recent origin or co-option by the host genome. Future studies focusing on comparative genomic and experimental data will be critical to understand the role of these ERVs in host genome evolution.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Advances in human norovirus research: Vaccines, genotype distribution and antiviral strategies 人类诺如病毒研究进展:疫苗、基因型分布和抗病毒策略。
IF 2.5 4区 医学
Virus research Pub Date : 2024-10-23 DOI: 10.1016/j.virusres.2024.199486
{"title":"Advances in human norovirus research: Vaccines, genotype distribution and antiviral strategies","authors":"","doi":"10.1016/j.virusres.2024.199486","DOIUrl":"10.1016/j.virusres.2024.199486","url":null,"abstract":"<div><div><em>Norovirus</em>, belonging to the <em>Caliciviridae</em> family, is a non-enveloped, positive-sense single-stranded RNA virus. It is widely acknowledged as a significant etiological agent responsible for non-bacterial acute gastroenteritis and considered a major cause thereof. <em>Norovirus</em> is primarily tranmitted via fecal-oral route, but can also be transmitted via airborne routes. Clinical manifestations often include symptoms associated with acute gastroenteritis, like nausea, vomiting, watery diarrhea, stomach cramps, and others. Due to the specific pathogenic mechanism of the virus, and genomic diversity, there are currently no preventive vaccines or effective antiviral drugs available for treating norovirus-induced acute gastroenteritis infections. The management of such infections mainly relies on oral rehydration therapy while prevention necessitates adherence to personal hygiene measures.</div><div>The present paper discusses the nature, transmission route, clinical manifestations, immune response mechanism, and vaccine research of <em>Norovirus</em>. The objective of this review manuscript is to systematically gather, analyze, and summarize recent research and investigations on norovirus in order to enhance our understanding of its characteristics and pathogenesis. This not only facilitates subsequent researchers in acquiring a more expedited and comprehensive grasp of the existing knowledge about norovirus but also provides clearer directions and goals for future studies.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Characterization of novel phage pK3–24 targeting multidrug-resistant Klebsiella pneumoniae and its therapeutic efficacy in Galleria mellonella larvae 针对耐多药肺炎克雷伯氏菌的新型噬菌体pK3-24的特征及其对鼠胆幼虫的疗效。
IF 2.5 4区 医学
Virus research Pub Date : 2024-10-20 DOI: 10.1016/j.virusres.2024.199481
{"title":"Characterization of novel phage pK3–24 targeting multidrug-resistant Klebsiella pneumoniae and its therapeutic efficacy in Galleria mellonella larvae","authors":"","doi":"10.1016/j.virusres.2024.199481","DOIUrl":"10.1016/j.virusres.2024.199481","url":null,"abstract":"<div><div><em>Klebsiella pneumoniae</em> is a common, conditionally pathogenic bacterium that often has a multidrug-resistant phenotype, leading to failure of antibiotic therapies. It can therefore induce serious diseases, including community-acquired pneumonia and bloodstream infections. As an emerging alternative to antibiotics, phages are considered key to solving the problem of drug-resistant bacterial infections. Here, we report a novel phage, pK3–24, that mainly targets ST447 <em>K. pneumoniae</em>. Phage pK3–24 is a T7-like short-tailed phage with a fast adsorption capacity that forms translucent plaques with halos on bacterial lawns. The optimal multiplicity of infection (MOI) is 0.01, and the average burst size is 50 PFU/mL. Phage pK3–24 shows environmental stability, surviving at below 50 °C and at pH values of 6–10. It has a double-stranded DNA genome of 40,327 bp and carries no antibiotic-resistance, virulence, or lysogeny genes. Phylogenetic analysis assigned phage pK3–24 to the genus <em>Przondovirus</em> as a new species. Phage pK3–24 inhibited the production of biofilm. Moreover, treatment with pK3–24 at doses with an MOI &gt; 1 effectively reduced the mortality of <em>Galleria mellonella</em> larvae infected with ST447 <em>K. pneumoniae</em>.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Diphyllin elicits a doubled-pronged attack on the entry of SARS-CoV-2 by inhibiting cathepsin L and furin 二氢霉素通过抑制螯合蛋白酶 L 和呋喃蛋白酶,对 SARS-CoV-2 的进入起到双管齐下的作用。
IF 2.5 4区 医学
Virus research Pub Date : 2024-10-19 DOI: 10.1016/j.virusres.2024.199485
{"title":"Diphyllin elicits a doubled-pronged attack on the entry of SARS-CoV-2 by inhibiting cathepsin L and furin","authors":"","doi":"10.1016/j.virusres.2024.199485","DOIUrl":"10.1016/j.virusres.2024.199485","url":null,"abstract":"<div><div>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic, posing serious threats to global health. Effective broad-spectrum antiviral drugs for the treatment of COVID-19 are not sufficiently available. In the present study, we investigated the antiviral activity of the natural lignan diphyllin (PubChem CID 100492) against different SARS-CoV-2 variants and explored the underlying molecular mechanisms. We found that diphyllin dose-dependently inhibits the SARS-CoV-2 spike (<em>S</em>)-mediated entry into different types of cells. The potent inhibition was evident against spike proteins derived from the original SARS-CoV-2 and from variants of concern such as Alpha, Beta, Delta or Omicron<em>.</em> Accordingly, diphyllin also significantly inhibited the <em>in vitro</em> infection of a clinical SARS-CoV-2 virus isolate. Mechanistically, diphyllin simultaneously inhibited the endosomal entry of SARS-CoV-2 by neutralizing the endosomal acidification and reducing the activity of the cysteine protease cathepsin L (CTSL) as well as S-meditated cell surface entry by impairing furin activity. Collectively, our findings establish diphyllin as novel inhibitor of CTSL and furin proteases, resulting in a double-pronged attack on SARS-CoV-2 entry along endosomal as well as cell surface routes. Therefore, diphyllin has the potential to be advanced as an inhibitor of SARS-CoV-2 entry.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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