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CXCR7 genetic variant predicts treatment response of pegylated-interferon α in HBeAg-positive chronic hepatitis B patients CXCR7 基因变异可预测 HBeAg 阳性慢性乙型肝炎患者对聚乙二醇干扰素 α 的治疗反应
IF 4.5 2区 医学
Antiviral research Pub Date : 2024-09-10 DOI: 10.1016/j.antiviral.2024.106005
Mengqi Luo , Xinghe Liang , Bin Zhou , Jinlin Hou , De-Ke Jiang
{"title":"CXCR7 genetic variant predicts treatment response of pegylated-interferon α in HBeAg-positive chronic hepatitis B patients","authors":"Mengqi Luo ,&nbsp;Xinghe Liang ,&nbsp;Bin Zhou ,&nbsp;Jinlin Hou ,&nbsp;De-Ke Jiang","doi":"10.1016/j.antiviral.2024.106005","DOIUrl":"10.1016/j.antiviral.2024.106005","url":null,"abstract":"<div><h3>Objectives</h3><p>CXC chemokine receptor 7 (CXCR7) plays pivotal roles in different virus infections. However, no research focused on the role of CXCR7 in hepatitis B virus (HBV)-infected patients. The primary aim of this study is to elucidate the role of CXCR7 in predicting the treatment response of chronic hepatitis B (CHB) patients undergoing pegylated interferon-alpha (PegIFNα) therapy.</p></div><div><h3>Methods</h3><p>Two cohorts with a total of 945 Chinese CHB patients (Cohort 1, n = 238; Cohort 2, n = 707) were enrolled in this retrospective study, all the patients were positive for hepatitis B e antigen (HBeAg) and received PegIFNα treatment for 48 weeks and followed-up for 24 weeks post-treatment. Nineteen tag single-nucleotide polymorphisms (SNPs) were selected within and surrounding the <em>CXCR7</em> gene region. The associations of <em>CXCR7</em> SNPs and polygenic score (PGS) with PegIFNα treatment response were investigated in the two cohorts.</p></div><div><h3>Results</h3><p>Among the 19 candidate SNPs of <em>CXCR7</em>, rs2952665 (A &gt; G) was significantly associated with combined response (CR, defined as HBeAg seroconversion and HBV DNA level &lt;3.3log<sub>10</sub>IU/mL, <em>P</em> = 0.002) and hepatitis B surface antigen (HBsAg) decline (<em>P</em> = 0.015) in the two cohorts at week 72. Furthermore, a PGS comprising <em>CXCR7</em>_rs2952665 and five additional SNPs, which were previously recognized as biomarkers of PegIFNα treatment response, demonstrated a robust correlation with both CR (<em>P</em> = 1.38 × 10<sup>−12</sup>) and HBsAg decline (<em>P</em> = 0.003) in all the patients.</p></div><div><h3>Conclusion</h3><p>This research illustrated that <em>CXCR7</em>_rs2952665 is a promising predictor of the PegIFNα therapy efficiency in Chinese HBeAg-positive CHB patients. A PGS consisting of <em>CXCR7</em>_rs2952665 and five previously reported SNPs predicts treatment response to PegIFNα better.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 106005"},"PeriodicalIF":4.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229495","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
MβCD inhibits SFTSV entry by disrupting lipid raft structure of the host cells MβCD 通过破坏宿主细胞的脂质筏结构抑制 SFTSV 的进入
IF 4.5 2区 医学
Antiviral research Pub Date : 2024-09-10 DOI: 10.1016/j.antiviral.2024.106004
Min Cheng , Rui Zhang , Jianshu Li , Wenyuan Ma , Linrun Li , Na Jiang , Bingxin Liu , Jing Wu , Nan Zheng , Zhiwei Wu
{"title":"MβCD inhibits SFTSV entry by disrupting lipid raft structure of the host cells","authors":"Min Cheng ,&nbsp;Rui Zhang ,&nbsp;Jianshu Li ,&nbsp;Wenyuan Ma ,&nbsp;Linrun Li ,&nbsp;Na Jiang ,&nbsp;Bingxin Liu ,&nbsp;Jing Wu ,&nbsp;Nan Zheng ,&nbsp;Zhiwei Wu","doi":"10.1016/j.antiviral.2024.106004","DOIUrl":"10.1016/j.antiviral.2024.106004","url":null,"abstract":"<div><p>Severe fever with thrombocytopenia syndrome virus (SFTSV), recently named as <em>Dabie bandavirus</em>, belongs to the family <em>Phenuiviridae</em> of the order <em>Bunyavirales</em>, is a newly-identified bunyavirus with a case fatality rate of up to 30%, posing a serious threat to public health. Lipid rafts on plasm membranes are important for the entry of enveloped viruses; however, the role of lipid rafts in bunyavirus entry remains unclear. In this study, we found that methyl-beta-cyclodextrin (MβCD), a drug that disrupts cholesterol in lipid rafts of cell membranes, inhibits SFTSV infection. Additionally, there is a back-complementary effect of SFTSV infection upon the addition of cholesterol. Moreover, the concentration of SFTSV particles in lipid rafts during entry directly indicated the role of lipid rafts as a gateway, whereas MβCD could inhibit SFTSV entry by affecting the structure of lipid rafts. In an in vivo study, MβCD also reduced the susceptibility of mice to SFTSV infection. Our results suggest that SFTSV can interact with Talin1 proteins on lipid rafts to enter host cells by endocytosis of lipid rafts and reveal the potential therapeutic value of MβCD for SFTSV infection.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 106004"},"PeriodicalIF":4.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167159","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
Bithiazole inhibitors of PI4KB show broad-spectrum antiviral activity against different viral families PI4KB 双噻唑抑制剂对不同病毒科具有广谱抗病毒活性
IF 4.5 2区 医学
Antiviral research Pub Date : 2024-09-10 DOI: 10.1016/j.antiviral.2024.106003
Maria Grazia Martina , Vincent Carlen , Sarah Van der Reysen , Elena Bianchi , Noemi Cabella , Emmanuele Crespan , Marco Radi , Valeria Cagno
{"title":"Bithiazole inhibitors of PI4KB show broad-spectrum antiviral activity against different viral families","authors":"Maria Grazia Martina ,&nbsp;Vincent Carlen ,&nbsp;Sarah Van der Reysen ,&nbsp;Elena Bianchi ,&nbsp;Noemi Cabella ,&nbsp;Emmanuele Crespan ,&nbsp;Marco Radi ,&nbsp;Valeria Cagno","doi":"10.1016/j.antiviral.2024.106003","DOIUrl":"10.1016/j.antiviral.2024.106003","url":null,"abstract":"<div><p>Broad-spectrum antivirals can be extremely important for pandemic preparedness. Targeting host factors dispensable for the host but indispensable for the virus can result in high barrier to resistance and a large range of viruses targeted. PI4KB is a lipid kinase involved in the replication of several RNA viruses, but common inhibitors of this target are mainly active against members of the <em>Picornaviridae</em> family. Herein we describe the optimization of bithiazole PI4KB inhibitors as broad-spectrum antivirals (BSAs) active against different members of the <em>Picornaviridae</em>, <em>Coronaviridae</em>, <em>Flaviviridae</em> and <em>Poxviridae</em> families. Since some of these viruses are transmitted via respiratory route, the efficacy of one of the most promising compounds was evaluated in an airway model. The molecule showed complete viral inhibition and absence of toxicity. These results pave the road for the development of new BSAs.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 106003"},"PeriodicalIF":4.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166354224002122/pdfft?md5=25a911d3e9f87dcf8a8f784e017ff140&pid=1-s2.0-S0166354224002122-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232860","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
Treatment efficacy of cidofovir and brincidofovir against clade II Monkeypox virus isolates 西多福韦和布林昔多福韦对第二型猴痘病毒分离株的治疗效果。
IF 4.5 2区 医学
Antiviral research Pub Date : 2024-09-05 DOI: 10.1016/j.antiviral.2024.105995
Jérémie Prévost , Angela Sloan , Yvon Deschambault , Nikesh Tailor , Kevin Tierney , Kimberly Azaransky , Srinivas Kammanadiminti , Douglas Barker , Shantha Kodihalli , David Safronetz
{"title":"Treatment efficacy of cidofovir and brincidofovir against clade II Monkeypox virus isolates","authors":"Jérémie Prévost ,&nbsp;Angela Sloan ,&nbsp;Yvon Deschambault ,&nbsp;Nikesh Tailor ,&nbsp;Kevin Tierney ,&nbsp;Kimberly Azaransky ,&nbsp;Srinivas Kammanadiminti ,&nbsp;Douglas Barker ,&nbsp;Shantha Kodihalli ,&nbsp;David Safronetz","doi":"10.1016/j.antiviral.2024.105995","DOIUrl":"10.1016/j.antiviral.2024.105995","url":null,"abstract":"<div><p>While historically confined to endemic areas, Monkeypox virus (MPXV) infection has increasingly garnered international attention due to sporadic outbreaks in non-endemic countries in the last two decades and its potential for human-to-human transmission. In 2022, a multi-country outbreak of mpox disease was declared by the World Health Organization (WHO) and nearly 100 000 mpox cases have been reported since the beginning of this pandemic. The clade II variant of the virus appears to be responsible for the vast majority of these infections. While there are no antiviral drugs currently approved to treat mpox specifically, the use of tecovirimat (TPOXX®) and brincidofovir (Tembexa®) is recommended by the Centers for Disease Control and Prevention (CDC) for compassionate use in severe mpox cases, since both are FDA-approved for the treatment of the closely related smallpox disease. Given the emergence of multiple tecovirimat-resistant infections, we aimed to evaluate the treatment efficacy of brincidofovir and its active compound, cidofovir, against MPXV clade II strains. Following intranasal infection, we show that cidofovir and brincidofovir can strongly reduce the viral replication of MPXV clade IIa and IIb viruses in the respiratory tract of susceptible mice when administered systemically and orally, respectively. The high antiviral activity of both compounds against historical and currently circulating MPXV strains supports their therapeutic potential for clinical application.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 105995"},"PeriodicalIF":4.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166354224002043/pdfft?md5=1e70e7d1d8050f2c5ebd4495a876d581&pid=1-s2.0-S0166354224002043-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144924","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
Dynamic features of virus protein 1 and substitutions in the 3-phenyl ring determine the potency and broad-spectrum activity of capsid-binding pyrazolo[3,4-d]pyrimidines against rhinoviruses 病毒蛋白 1 的动态特征和 3-苯基环的取代决定了与囊膜结合的吡唑并[3,4-d]嘧啶对鼻病毒的效力和广谱活性。
IF 4.5 2区 医学
Antiviral research Pub Date : 2024-09-03 DOI: 10.1016/j.antiviral.2024.105993
Martina Richter , Maria Khrenova , Elena Kazakova , Olga Riabova , Anna Egorova , Vadim Makarov , Michaela Schmidtke
{"title":"Dynamic features of virus protein 1 and substitutions in the 3-phenyl ring determine the potency and broad-spectrum activity of capsid-binding pyrazolo[3,4-d]pyrimidines against rhinoviruses","authors":"Martina Richter ,&nbsp;Maria Khrenova ,&nbsp;Elena Kazakova ,&nbsp;Olga Riabova ,&nbsp;Anna Egorova ,&nbsp;Vadim Makarov ,&nbsp;Michaela Schmidtke","doi":"10.1016/j.antiviral.2024.105993","DOIUrl":"10.1016/j.antiviral.2024.105993","url":null,"abstract":"<div><p>Pyrazolo[3,4-<em>d</em>]pyrimidines represent one potent class of well tolerated and highly active rhinovirus (RV) inhibitors that act as capsid binders. The lead compound OBR-5-340 inhibits a broad-spectrum of RVs. Aiming to improve lead activity, we evaluated the impact of structural modifications in the 3-phenyl ring of OBR-5-340 on its potency and spectrum of anti-RV activity <em>vitro</em>. Our results demonstrate the crucial role of substitution at position 4 for strong, broad-spectrum anti-RV activity. The 4-methyl (RCB23137) and 4-chloro (RCB23138) derivatives outperformed OBR-5-340 in terms of potency and anti-RV activity spectrum. Based on these findings, the compounds were selected for computational binding studies. Molecular dynamic simulations with six RVs differing in OBR-5-340, RCB23137, and RCB23138 sensitivity proved the impact of dynamic features of two VP1 loops enveloping these inhibitors on antiviral potency.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 105993"},"PeriodicalIF":4.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016635422400202X/pdfft?md5=b1c2a35e05455c411efbb1f2c1d4fecc&pid=1-s2.0-S016635422400202X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131681","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 triple combination of Remdesivir (GS-441524), Molnupiravir and Ribavirin is highly efficient in inhibiting coronavirus replication in human nasal airway epithelial cell cultures and in a hamster infection model 雷米替韦(GS-441524)、莫诺吡拉韦和利巴韦林的三联疗法能高效抑制冠状病毒在人鼻气道上皮细胞培养物和仓鼠感染模型中的复制。
IF 4.5 2区 医学
Antiviral research Pub Date : 2024-09-03 DOI: 10.1016/j.antiviral.2024.105994
Thuc Nguyen Dan Do , Rana Abdelnabi , Bernadett Boda , Samuel Constant , Johan Neyts , Dirk Jochmans
{"title":"The triple combination of Remdesivir (GS-441524), Molnupiravir and Ribavirin is highly efficient in inhibiting coronavirus replication in human nasal airway epithelial cell cultures and in a hamster infection model","authors":"Thuc Nguyen Dan Do ,&nbsp;Rana Abdelnabi ,&nbsp;Bernadett Boda ,&nbsp;Samuel Constant ,&nbsp;Johan Neyts ,&nbsp;Dirk Jochmans","doi":"10.1016/j.antiviral.2024.105994","DOIUrl":"10.1016/j.antiviral.2024.105994","url":null,"abstract":"<div><p>The use of fixed dose-combinations of antivirals with different mechanisms of action has proven key in the successful treatment of infections with HIV and HCV. For the treatment of infections with SARS-CoV-2 and possible future epi-/pandemic coronaviruses, it will be important to explore the efficacy of combinations of different drugs, in particular to avoid resistance development, such as in patients with immunodeficiencies. This work explores the effect of a combination of 3 broad-spectrum antiviral nucleosides on the replication of coronaviruses. To that end, we made use of primary human airway epithelial cell (HAEC) cultures grown at the air-liquid interface that were infected with the beta coronavirus OC43. We found that the triple combination of GS-441524 (the parent nucleoside of remdesivir), molnupiravir and ribavirin resulted in a more pronounced antiviral efficacy than what could be expected from a purely additive antiviral effect. The potency of this triple combination was next tested in SARS-CoV-2 infected hamsters in a prophylactic setup. To that end, for each of the drugs, intentionally suboptimal or even ineffective doses were selected. Yet, in the lungs of all hamsters that received triple prophylactic therapy (but not in those that received the respective double combinations) no infectious virus was detectable. Our findings indicate that co-administration of approved drugs for the treatment of coronavirus infections should be further explored but also against other families of viruses with epidemic and pandemic potential for which no effective antiviral treatment is available.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 105994"},"PeriodicalIF":4.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166354224002031/pdfft?md5=75eca4369d31dca76a301be203c81926&pid=1-s2.0-S0166354224002031-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139141","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
Coronavirus nucleocapsid-based vaccine provides partial protection against hetero-species coronavirus in murine models 基于冠状病毒核壳的疫苗可在小鼠模型中提供针对异种冠状病毒的部分保护。
IF 4.5 2区 医学
Antiviral research Pub Date : 2024-08-23 DOI: 10.1016/j.antiviral.2024.105991
Pureum Lee , Jihee Kim , Hanseul Oh , Chang-Ung Kim , Ahn Young Jeong , Moo-Seung Lee , Min Seong Jang , Jung Joo Hong , Jung-Eun Park , Doo-Jin Kim
{"title":"Coronavirus nucleocapsid-based vaccine provides partial protection against hetero-species coronavirus in murine models","authors":"Pureum Lee ,&nbsp;Jihee Kim ,&nbsp;Hanseul Oh ,&nbsp;Chang-Ung Kim ,&nbsp;Ahn Young Jeong ,&nbsp;Moo-Seung Lee ,&nbsp;Min Seong Jang ,&nbsp;Jung Joo Hong ,&nbsp;Jung-Eun Park ,&nbsp;Doo-Jin Kim","doi":"10.1016/j.antiviral.2024.105991","DOIUrl":"10.1016/j.antiviral.2024.105991","url":null,"abstract":"<div><p>Most coronavirus vaccines focus on the spike (S) antigen, but the frequent mutations in S raise concerns about the vaccine efficacy against new variants. Although additional antigens with conserved sequences are have been tested, the extent to which these vaccines can provide immunity against different coronavirus species remains unclear. In this study, we assessed the potential of nucleocapsid (N) as a coronavirus vaccine antigen. Immunization with MERS-CoV N induced robust immune responses, providing significant protection against MERS-CoV. Notably, MERS-CoV N elicited cross-reactive T cell responses to SARS-CoV-2 N and significantly reduced lung inflammation following a SARS-CoV-2 challenge in the transient hACE2 mouse model. However, in K18-hACE transgenic mice, the vaccine showed limited protection. Collectively, our findings suggest that coronavirus N can be an effective vaccine antigen against homologous viruses, but its efficacy may vary across different coronaviruses, highlighting the need for further research on pan-coronavirus vaccines using conserved antigens.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 105991"},"PeriodicalIF":4.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054774","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
Anti-SARS-CoV-2 gapmer antisense oligonucleotides targeting the main protease region of viral RNA 针对病毒 RNA 主要蛋白酶区的抗 SARS-CoV-2 gapmer 反义寡核苷酸。
IF 4.5 2区 医学
Antiviral research Pub Date : 2024-08-23 DOI: 10.1016/j.antiviral.2024.105992
Masako Yamasaki , Wakana Saso , Takuya Yamamoto , Masayoshi Sato , Hiroko Takagi , Tetsuya Hasegawa , Yuji Kozakura , Hiroyuki Yokoi , Hirofumi Ohashi , Kana Tsuchimoto , Rina Hashimoto , Shuetsu Fukushi , Akihiko Uda , Masamichi Muramatsu , Kazuo Takayama , Ken Maeda , Yoshimasa Takahashi , Tsuyoshi Nagase , Koichi Watashi
{"title":"Anti-SARS-CoV-2 gapmer antisense oligonucleotides targeting the main protease region of viral RNA","authors":"Masako Yamasaki ,&nbsp;Wakana Saso ,&nbsp;Takuya Yamamoto ,&nbsp;Masayoshi Sato ,&nbsp;Hiroko Takagi ,&nbsp;Tetsuya Hasegawa ,&nbsp;Yuji Kozakura ,&nbsp;Hiroyuki Yokoi ,&nbsp;Hirofumi Ohashi ,&nbsp;Kana Tsuchimoto ,&nbsp;Rina Hashimoto ,&nbsp;Shuetsu Fukushi ,&nbsp;Akihiko Uda ,&nbsp;Masamichi Muramatsu ,&nbsp;Kazuo Takayama ,&nbsp;Ken Maeda ,&nbsp;Yoshimasa Takahashi ,&nbsp;Tsuyoshi Nagase ,&nbsp;Koichi Watashi","doi":"10.1016/j.antiviral.2024.105992","DOIUrl":"10.1016/j.antiviral.2024.105992","url":null,"abstract":"<div><p>Given the worldwide risk for the outbreak of emerging/re-emerging respiratory viruses, establishment of new antiviral strategies is greatly demanded. In this study, we present a scheme to identify gapmer antisense oligonucleotides (ASOs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA that efficiently inhibit viral replication. We synthesized approximately 300 gapmer ASOs designed to target various SARS-CoV-2 RNA regions and evaluated their activity in cell-based assays. Through a multistep screening in cell culture systems, we identified that ASO#41, targeting the coding region for viral main protease, reduced SARS-CoV-2 RNA levels in infected cells and inhibited virus-induced cytopathic effects. Antiviral effect of ASO#41 was also observed in iPS cell-derived human lung organoids. ASO#41 depleted intracellular viral RNAs during genome replication in an endogenous RNaseH-dependent manner. ASO#41 showed a wide range of antiviral activity against SARS-CoV-2 variants of concern including Alpha, Delta, and Omicron. Intranasal administration to mice exhibited intracellular accumulation of ASO#41 in the lung and significantly reduced the viral infectious titer, with milder body weight loss due to SARS-CoV-2 infection. Further chemical modification with phosphoryl guanidine-containing backbone linkages provided an elevation of anti-SARS-CoV-2 activity, with 23.4 nM of 50% antiviral inhibitory concentration, one of the strongest anti-SARS-CoV-2 ASOs reported so far. Our study presents an approach to identify active ASOs against SARS-CoV-2, which is potentially useful for establishing an antiviral strategy by targeting genome RNA of respiratory viruses.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"230 ","pages":"Article 105992"},"PeriodicalIF":4.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054773","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
Import of extracellular 2′-3′cGAMP by the folate transporter, SLC19A1, establishes an antiviral response that limits herpes simplex virus-1 叶酸转运体 SLC19A1 导入细胞外 2'-3'cGAMP 可建立抗病毒反应,限制单纯疱疹病毒-1。
IF 4.5 2区 医学
Antiviral research Pub Date : 2024-08-21 DOI: 10.1016/j.antiviral.2024.105989
Zsuzsa K. Szemere, Eain A. Murphy
{"title":"Import of extracellular 2′-3′cGAMP by the folate transporter, SLC19A1, establishes an antiviral response that limits herpes simplex virus-1","authors":"Zsuzsa K. Szemere,&nbsp;Eain A. Murphy","doi":"10.1016/j.antiviral.2024.105989","DOIUrl":"10.1016/j.antiviral.2024.105989","url":null,"abstract":"<div><p>Recently it was discovered that extracellular 2′-3′cGAMP can activate the STING pathway in a cGAS-independent fashion by being transported across the cell membrane via the folate transporter, SLC19A1, the first identified extracellular antiporter of this critical signaling molecule in cancer cells. We hypothesized that this non-canonical activation of STING pathway would function to establish an antiviral state similar to that seen with the paracrine antiviral activities of interferon. Herein, we report that treatment of the monocytic cell line, THP-1 cells and SH-SY5Y neuronal cell line with exogenous 2′-3′cGAMP induces interferon production and establishes an antiviral state that limits herpes simplex virus-1 (HSV-1), a ubiquitous virus with high seropositivity in the human population. Using either pharmaceutical inhibition or genetic knockout of SLC19A1 blocks the 2′-3′cGAMP-induced inhibition of viral replication. Our data indicate SLC19A1 functions as a newly identified antiviral mediator for extracellular 2′-3′cGAMP. This work presents novel and important findings about an antiviral mechanism which information could aid in the development of better antiviral drugs in the future.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"230 ","pages":"Article 105989"},"PeriodicalIF":4.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999370","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
A novel live DNA tagging system for African swine fever virus shows that bisbenzimide Hoechst 33342 can effectively block its replication 一种新型非洲猪瘟病毒活 DNA 标记系统显示,双苯亚胺 Hoechst 33342 能有效阻断非洲猪瘟病毒的复制
IF 4.5 2区 医学
Antiviral research Pub Date : 2024-08-19 DOI: 10.1016/j.antiviral.2024.105973
Veronica Martin , Beatriz Guerra , Bruno Hernaez , Sandrine Kappler-Gratias , Franck Gallardo , Milagros Guerra , German Andres , Ali Alejo
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