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Flavivirus nonstructural proteins and replication complexes as antiviral drug targets 黄病毒非结构蛋白和复制复合体作为抗病毒药物靶点
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-04-01 DOI: 10.1016/j.coviro.2023.101305
Kaïn van den Elsen , Bing Liang Alvin Chew , Jun Sheng Ho , Dahai Luo
{"title":"Flavivirus nonstructural proteins and replication complexes as antiviral drug targets","authors":"Kaïn van den Elsen ,&nbsp;Bing Liang Alvin Chew ,&nbsp;Jun Sheng Ho ,&nbsp;Dahai Luo","doi":"10.1016/j.coviro.2023.101305","DOIUrl":"10.1016/j.coviro.2023.101305","url":null,"abstract":"<div><p>Many flaviviruses are well-known pathogens, such as dengue, Zika, Japanese encephalitis, and yellow fever viruses. Among them, dengue viruses cause global epidemics and threaten billions of people. Effective vaccines and antivirals are in desperate need. In this review, we focus on the recent advances in understanding viral nonstructural (NS) proteins as antiviral drug targets. We briefly summarize the experimental structures and predicted models of flaviviral NS proteins and their functions. We highlight a few well-characterized inhibitors targeting these NS proteins and provide an update about the latest development. NS4B emerges as one of the most promising drug targets as novel inhibitors targeting NS4B and its interaction network are entering clinical studies. Studies aiming to elucidate the architecture and molecular basis of viral replication will offer new opportunities for novel antiviral discovery. Direct-acting agents against dengue and other pathogenic flaviviruses may be available very soon.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"59 ","pages":"Article 101305"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9624964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
HIV persistence: silence or resistance? 艾滋病毒的持久性：沉默还是抵抗？
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-04-01 DOI: 10.1016/j.coviro.2023.101301
Alexander O Pasternak, Ben Berkhout
{"title":"HIV persistence: silence or resistance?","authors":"Alexander O Pasternak,&nbsp;Ben Berkhout","doi":"10.1016/j.coviro.2023.101301","DOIUrl":"10.1016/j.coviro.2023.101301","url":null,"abstract":"<div><p>Despite decades of suppressive antiretroviral therapy, human immunodeficiency virus (HIV) reservoirs in infected individuals persist and fuel viral rebound once therapy is interrupted. The persistence of viral reservoirs is the main obstacle to achieving HIV eradication or a long-term remission. The last decade has seen a profound change in our understanding of the mechanisms behind HIV persistence, which appears to be much more complex than originally assumed. In addition to the persistence of transcriptionally silent proviruses in a stable latent reservoir that is invisible to the immune system, HIV is increasingly recognized to persist by resistance to the immune clearance, which appears to play a surprisingly prominent role in shaping the reservoir. In this review, we discuss some emerging insights into the mechanisms of HIV persistence, as well as their implications for the development of strategies towards an HIV cure.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"59 ","pages":"Article 101301"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9248884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Interplay of RNA 2′-O-methylations with viral replication RNA 2′-O-甲基化与病毒复制的相互作用
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-04-01 DOI: 10.1016/j.coviro.2023.101302
Alice Decombe, Priscila El Kazzi, Etienne Decroly
{"title":"Interplay of RNA 2′-O-methylations with viral replication","authors":"Alice Decombe,&nbsp;Priscila El Kazzi,&nbsp;Etienne Decroly","doi":"10.1016/j.coviro.2023.101302","DOIUrl":"10.1016/j.coviro.2023.101302","url":null,"abstract":"<div><p>Viral RNAs (vRNAs) are decorated by post-transcriptional modifications, including methylation of nucleotides. Methylations regulate biological functions linked to the sequence, structure, and protein interactome of RNA. Several RNA viruses were found to harbor 2′-O-methylations, affecting the ribose moiety of RNA. This mark was initially shown to target the first and second nucleotides of the 5′-end cap structure of mRNA. More recently, nucleotides within vRNA were also reported to carry 2′-O-methylations. The consequences of such methylations are still puzzling since they were associated with both proviral and antiviral effects. Here, we focus on the mechanisms governing vRNA 2′-O-methylation and we explore the possible roles of this epitranscriptomic modification for viral replication.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"59 ","pages":"Article 101302"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9261650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
MEK inhibitors as novel host-targeted antivirals with a dual-benefit mode of action against hyperinflammatory respiratory viral diseases MEK抑制剂作为一种新的宿主靶向抗病毒药物，对高炎症性呼吸道病毒性疾病具有双重益处
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-04-01 DOI: 10.1016/j.coviro.2023.101304
Stephan Ludwig , Stephan Pleschka , Oliver Planz
{"title":"MEK inhibitors as novel host-targeted antivirals with a dual-benefit mode of action against hyperinflammatory respiratory viral diseases","authors":"Stephan Ludwig ,&nbsp;Stephan Pleschka ,&nbsp;Oliver Planz","doi":"10.1016/j.coviro.2023.101304","DOIUrl":"10.1016/j.coviro.2023.101304","url":null,"abstract":"<div><p>Acute hyperinflammatory virus infections, such as influenza or coronavirus disease-19, are still a major health burden worldwide. In these diseases, a massive overproduction of pro-inflammatory cytokines and chemokines (cytokine storm syndrome) determine the severity of the disease, especially in late stages. Direct-acting antivirals against these pathogens have to be administered very early after infection to be effective and may induce viral resistance. Here, we summarize data on a host-targeted strategy using inhibitors of the cellular Raf/MEK/ERK kinase cascade that not only block replication of different RNA viruses but also suppress the hyperinflammatory cytokine response upon infection. In the first phase-II clinical trial of that approach, the MEK inhibitor Zapnometinib shows evidence of clinical benefit.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"59 ","pages":"Article 101304"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9298283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of influenza-A virus and coronavirus viral glycoprotein cleavage in host adaptation 流感a- a病毒和冠状病毒糖蛋白裂解在宿主适应中的作用
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-02-01 DOI: 10.1016/j.coviro.2023.101303
Miriam R Heindl, Eva Böttcher-Friebertshäuser
{"title":"The role of influenza-A virus and coronavirus viral glycoprotein cleavage in host adaptation","authors":"Miriam R Heindl,&nbsp;Eva Böttcher-Friebertshäuser","doi":"10.1016/j.coviro.2023.101303","DOIUrl":"10.1016/j.coviro.2023.101303","url":null,"abstract":"<div><p>While receptor binding is well recognized as a factor in influenza-A virus (IAV) and coronavirus (CoV) host adaptation, the role of viral glycoprotein cleavage has not been studied in detail so far. Interestingly, recent studies suggest that host species may differ in their protease repertoire available for cleavage. Furthermore, it was shown for certain bat-derived CoVs that proteolytic activation provides a critical barrier to infect human cells. Understanding the role of glycoprotein cleavage in different species and how IAV and CoVs adapt to a new protease repertoire may allow evaluating the zoonotic potential and risk posed by these viruses. Here, we summarize the current knowledge on the emergence of a multibasic cleavage site (CS) in the glycoproteins of IAVs and CoVs in different host species. Additionally, we discuss the role of transmembrane serine protease 2 (TMPRSS2) in virus activation and entry and a role of neuropilin-1 in acquisition of a multibasic CS in different hosts.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"58 ","pages":"Article 101303"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9847222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9299542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of the animal host in the management of bacteriophage resistance during phage therapy 动物宿主在噬菌体治疗过程中管理噬菌体耐药性的作用
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-02-01 DOI: 10.1016/j.coviro.2022.101290
Baptiste Gaborieau , Laurent Debarbieux
{"title":"The role of the animal host in the management of bacteriophage resistance during phage therapy","authors":"Baptiste Gaborieau ,&nbsp;Laurent Debarbieux","doi":"10.1016/j.coviro.2022.101290","DOIUrl":"10.1016/j.coviro.2022.101290","url":null,"abstract":"<div><p>Multi-drug-resistant bacteria are associated with significantly higher morbidity and mortality. The possibilities for discovering new antibiotics are limited, but phage therapy — the use of bacteriophages (viruses infecting bacteria) to cure infections — is now being investigated as an alternative or complementary treatment to antibiotics. However, one of the major limitations of this approach lies in the antagonistic coevolution between bacteria and bacteriophages, which determines the ultimate success or failure of phage therapy. Here, we review the possible influence of the animal host on phage resistance and its consequences for the efficacy of phage therapy. We also discuss the value of <em>in vitro</em> assays for anticipating the dynamics of phage resistance observed <em>in vivo</em>.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"58 ","pages":"Article 101290"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9255236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Advances in the treatment of HTLV-1-associated adult T-cell leukemia lymphoma HTLV-1相关成人T细胞白血病淋巴瘤的治疗进展
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-02-01 DOI: 10.1016/j.coviro.2022.101289
Adrienne A Phillips
{"title":"Advances in the treatment of HTLV-1-associated adult T-cell leukemia lymphoma","authors":"Adrienne A Phillips","doi":"10.1016/j.coviro.2022.101289","DOIUrl":"10.1016/j.coviro.2022.101289","url":null,"abstract":"<div><p>Adult T-cell leukemia/lymphoma (ATLL) is an aggressive hematologic malignancy linked to HTLV-1 infection, which is refractory to therapy. The precise mechanism of oncogenesis in ATLL is incompletely understood, however, oncogenic viral genes Tax and Hbz are implicated, and recent large genomic and transcriptome studies provide further insight. Despite progress in understanding the disease, survival and outcome with current therapies remain poor. Long-term survivors are reported, primarily among those with indolent disease or activating CC chemokine receptor 4 mutations, however, allogeneic hematopoietic stem cell transplant is the only curative treatment option. The majority of patients succumb to their disease and ongoing and collaborative research efforts are needed. I will review recent updates in HTLV-1-associated ATLL epidemiology, pathogenesis, therapy, and prevention.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"58 ","pages":"Article 101289"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9254612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Paramyxoviruses from bats: changes in receptor specificity and their role in host adaptation 蝙蝠副粘病毒:受体特异性的变化及其在宿主适应中的作用
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-02-01 DOI: 10.1016/j.coviro.2022.101292
Griffin D Haas, Benhur Lee
{"title":"Paramyxoviruses from bats: changes in receptor specificity and their role in host adaptation","authors":"Griffin D Haas,&nbsp;Benhur Lee","doi":"10.1016/j.coviro.2022.101292","DOIUrl":"10.1016/j.coviro.2022.101292","url":null,"abstract":"<div><p>Global metagenomic surveys have revealed that bats host a diverse array of paramyxoviruses, including species from at least five major genera. An essential determinant of successful spillover is the entry of a virus into a new host. We evaluate the role of receptor usage in the zoonotic potential of bat-borne henipaviruses, morbilliviruses, pararubulaviruses, orthorubulaviruses, and jeilongviruses; successful spillover into humans depends upon compatibility of a respective viral attachment protein with its cognate receptor. We also emphasize the importance of postentry restrictions in preventing spillover. Metagenomics and characterization of newly identified paramyxoviruses have greatly improved our understanding of spillover determinants, allowing for better forecasts of which bat-borne viruses may pose the greatest risk for cross-species transmission into humans.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"58 ","pages":"Article 101292"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9974588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9308742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Editorial overview: Special issue on phage therapy 编辑综述：噬菌体治疗特刊
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-02-01 DOI: 10.1016/j.coviro.2022.101300
Joana Azeredo , Jean Paul Pirnay
{"title":"Editorial overview: Special issue on phage therapy","authors":"Joana Azeredo ,&nbsp;Jean Paul Pirnay","doi":"10.1016/j.coviro.2022.101300","DOIUrl":"10.1016/j.coviro.2022.101300","url":null,"abstract":"","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"58 ","pages":"Article 101300"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9247808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Proteomic analysis of antiviral innate immunity 抗病毒先天免疫的蛋白质组学分析
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-02-01 DOI: 10.1016/j.coviro.2022.101291
Jonas D Albarnaz, Michael P Weekes
{"title":"Proteomic analysis of antiviral innate immunity","authors":"Jonas D Albarnaz,&nbsp;Michael P Weekes","doi":"10.1016/j.coviro.2022.101291","DOIUrl":"10.1016/j.coviro.2022.101291","url":null,"abstract":"<div><p>The capacity of host cells to detect and restrict an infecting virus rests on an array of cell-autonomous antiviral effectors and innate immune receptors that can trigger inflammatory processes at tissue and organismal levels. Dynamic changes in protein abundance, subcellular localisation, post-translational modifications and interactions with other biomolecules govern these processes. Proteomics is therefore an ideal experimental tool to discover novel mechanisms of host antiviral immunity. Additional information can be gleaned both about host and virus by systematic analysis of viral immune evasion strategies. In this review, we summarise recent advances in proteomic technologies and their application to antiviral innate immunity.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"58 ","pages":"Article 101291"},"PeriodicalIF":5.9,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9247792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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