Antiviral research最新文献_第2页

Corrigendum to “Discovery of ZFD-10 of a pyridazino[4,5-b]indol-4(5H)-one derivative as an anti-ZIKV agent and a ZIKV NS5 RdRp inhibitor” [Antivir. Res. 214 (2023) 105607] 对 "发现哒嗪并[4,5-b]吲哚-4(5H)-酮衍生物 ZFD-10 作为抗 ZIKV 药物和 ZIKV NS5 RdRp 抑制剂 "的更正[Antivir. Res. 214 (2023) 105607]。

IF 4.5 2区医学

Antiviral research Pub Date : 2024-11-01 DOI: 10.1016/j.antiviral.2024.106025

Guang-Feng Zhou , Weiyi Qian , Feng Li , Ren-Hua Yang , Na Wang , Chang-Bo Zheng , Chun-Yan Li , Xue-Rong Gu , Liu-Meng Yang , Jinsong Liu , Si-Dong Xiong , Guo-Chun Zhou , Yong-Tang Zheng

引用次数: 0

Oral 3CL protease inhibitor ensitrelvir suppressed SARS-CoV-2 shedding and infection in a hamster aerosol transmission model 口服 3CL 蛋白酶抑制剂 ensitrelvir 可抑制仓鼠气溶胶传播模型中 SARS-CoV-2 的脱落和感染。

IF 4.5 2区医学

Antiviral research Pub Date : 2024-10-29 DOI: 10.1016/j.antiviral.2024.106026

Masaaki Nakashima , Haruaki Nobori , Takayuki Kuroda , Alice Shimba , Satoshi Miyagawa , Akane Hayashi , Kazumi Matsumoto , Mei Yoshida , Kaoru Baba , Teruhisa Kato , Keita Fukao

{"title":"Oral 3CL protease inhibitor ensitrelvir suppressed SARS-CoV-2 shedding and infection in a hamster aerosol transmission model","authors":"Masaaki Nakashima , Haruaki Nobori , Takayuki Kuroda , Alice Shimba , Satoshi Miyagawa , Akane Hayashi , Kazumi Matsumoto , Mei Yoshida , Kaoru Baba , Teruhisa Kato , Keita Fukao","doi":"10.1016/j.antiviral.2024.106026","DOIUrl":"10.1016/j.antiviral.2024.106026","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) remain a major global health challenge, with aerosol transmission being the primary route of spread. The use of antivirals as medical countermeasures to control SARS-CoV-2 transmission and spread is promising but remains to be clarified. The current study established and used an <em>in vivo</em> hamster aerosol transmission model system to evaluate the efficacy of the protease inhibitor ensitrelvir to prevent the spread of SARS-CoV-2. Male Index Syrian hamsters were intranasally infected with SARS-CoV-2, paired with naïve Contact hamsters, and co-housed for 12 h under conditions to allow for only aerosol transmission. The Index hamsters were treated three times with ensitrelvir starting 8 h post infection, or the Contact hamsters were treated once with ensitrelvir 12 h prior to co-housing. Viral infection and transmission were monitored by evaluating nasal lavage fluid, lung tissues, and body and lung weights. Post-infection administration of ensitrelvir to Index hamsters suppressed virus shedding in a dose-dependent manner. Pre-exposure administration of 750 mg/kg ensitrelvir to naïve Contact hamsters also protected against aerosol SARS-CoV-2 infection in a dose-dependent manner. Furthermore, pre-exposure treatment of 750 mg/kg ensitrelvir supressed body weight loss and lung weight increase of aerosol infected hamsters compared to vehicle-treated hamsters. These findings suggest that ensitrelvir may prevent SARS-CoV-2 spread when administered to infected patients and may prevent or limit SARS-CoV-2 infection when prophylactically administered to non-infected individuals. Both approaches may help protect at-risk individuals, such as family members living with SARS-CoV-2-infected patients.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"232 ","pages":"Article 106026"},"PeriodicalIF":4.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543353","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

SiRNAs as antiviral drugs – Current status, therapeutic potential and challenges 作为抗病毒药物的 SiRNA - 现状、治疗潜力和挑战。

IF 4.5 2区医学

Antiviral research Pub Date : 2024-10-23 DOI: 10.1016/j.antiviral.2024.106024

Trairong Chokwassanasakulkit , Victor Baba Oti , Adi Idris , Nigel AJ. McMillan

引用次数: 0

Vemurafenib inhibits the replication of diabetogenic enteroviruses in intestinal epithelial and pancreatic beta cells 维莫非尼抑制致糖尿病肠道病毒在肠上皮细胞和胰腺β细胞中的复制。

IF 4.5 2区医学

Antiviral research Pub Date : 2024-10-15 DOI: 10.1016/j.antiviral.2024.106021

Marta Butrym , Fabian Byvald , Marfa Blanter , Emma E. Ringqvist , Svitlana Vasylovska , Varpu Marjomäki , Joey Lau , Virginia M. Stone , Malin Flodström-Tullberg

{"title":"Vemurafenib inhibits the replication of diabetogenic enteroviruses in intestinal epithelial and pancreatic beta cells","authors":"Marta Butrym , Fabian Byvald , Marfa Blanter , Emma E. Ringqvist , Svitlana Vasylovska , Varpu Marjomäki , Joey Lau , Virginia M. Stone , Malin Flodström-Tullberg","doi":"10.1016/j.antiviral.2024.106021","DOIUrl":"10.1016/j.antiviral.2024.106021","url":null,"abstract":"<div><div>Enteroviruses, which infect via the gut, have been implicated in type 1 diabetes (T1D) development. Prolonged faecal shedding of enterovirus has been associated with islet autoimmunity. Additionally, enteroviral proteins and viral RNA have been detected in the pancreatic islets of individuals with recent-onset T1D, implicating their possible role in beta cell destruction. Despite this, no approved antiviral drugs currently exist that specifically target enterovirus infections for utilisation in disease interventions.</div><div>Drug repurposing allows for the discovery of new clinical uses for existing drugs and can expedite drug discovery. Previously, the cancer drug Vemurafenib demonstrated unprecedented antiviral activity against several enteroviruses. In the present study, we assessed the efficacy of Vemurafenib and an analogue thereof in preventing infection or reducing the replication of enteroviruses associated with T1D. We tested Vemurafenib in intestinal epithelial cells (IECs) and insulin-producing beta cells. Additionally, we established a protocol for infecting human stem cell-derived islets (SC-islets) and used Vemurafenib and its analogue in this model.</div><div>Our studies revealed that Vemurafenib exhibited strong antiviral properties in IECs and a beta cell line. The antiviral effect was also seen with the Vemurafenib analogue. SC-islets expressed the viral receptors CAR and DAF, with their highest expression in insulin- and glucagon-positive cells, respectively. SC-islets were successfully infected by CVBs and the antiviral activity of Vemurafenib and its analogue was confirmed in most SC-islet batches.</div><div>In summary, our observations suggest that Vemurafenib and its analogue warrant further exploration as potential antiviral agents for the treatment of enterovirus-induced diseases, including T1D.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 106021"},"PeriodicalIF":4.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456785","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

Bictegravir alters glucose tolerance in vivo and causes hepatic mitochondrial dysfunction 比特拉韦会改变体内葡萄糖耐量并导致肝线粒体功能障碍。

IF 4.5 2区医学

Antiviral research Pub Date : 2024-10-15 DOI: 10.1016/j.antiviral.2024.106020

Patricia García-Martínez , Laura Gisbert-Ferrándiz , Ángeles Álvarez , Juan V. Esplugues , Ana Blas-García

{"title":"Bictegravir alters glucose tolerance in vivo and causes hepatic mitochondrial dysfunction","authors":"Patricia García-Martínez , Laura Gisbert-Ferrándiz , Ángeles Álvarez , Juan V. Esplugues , Ana Blas-García","doi":"10.1016/j.antiviral.2024.106020","DOIUrl":"10.1016/j.antiviral.2024.106020","url":null,"abstract":"<div><div>Growing evidence associates antiretroviral therapies containing integrase strand transfer inhibitors or tenofovir alafenamide (TAF) with increased weight gain and metabolic diseases, but the underlying mechanisms remain unclear. This study evaluated the impact of lamivudine, dolutegravir (DTG), bictegravir (BIC), tenofovir disoproxil fumarate, and TAF on metabolic alterations, and explored glucose homeostasis and mitochondrial stress as potential mechanisms. These pathways were analyzed both <em>in vivo</em> (C57BL/6J mice treated with the abovementioned drugs or vehicle for 16 weeks) and <em>in vitro</em> (in Hep3B cells). Mice treated with BIC exhibited higher glucose levels and a slower decrease during a glucose tolerance test. Functional enrichment analyses of livers from antiretroviral-treated mice revealed that only BIC altered the cellular response to insulin and induced a gluconeogenic-favoring profile, with <em>Fgf21</em> playing a significant role. <em>In vitro</em>, BIC significantly reduced hepatocyte glucose uptake in a concentration-dependent manner, both under basal conditions and post-insulin stimulation, while the other drugs produced no significant changes. Hep3B cells treated with clinically relevant concentrations of BIC exhibited significant alterations in the mRNA expression of enzymes related to glucose metabolism. Both DTG and BIC reduced mitochondrial dehydrogenase activity, but only BIC increased reactive oxygen species, mitochondrial membrane potential, and cellular granularity, thereby indicating mitochondrial stress. BIC promoted mitochondrial dysfunction, modified carbohydrate metabolism and glucose consumption in hepatocytes, and altered glucose tolerance and gluconeogenesis regulation in mice. These findings suggest that BIC contributes to insulin resistance and diabetes in people living with HIV, warranting clinical studies to clarify its association with carbohydrate metabolism disorders.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 106020"},"PeriodicalIF":4.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456786","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

Circulating capsid-antibody-complexes (CACs) drive intrahepatic complement deposition and inform subclinical liver inflammation in chronic hepatitis B 循环中的囊膜抗体复合物（CAC）驱动肝内补体沉积，为慢性乙型肝炎的亚临床肝脏炎症提供信息

IF 4.5 2区医学

Antiviral research Pub Date : 2024-10-11 DOI: 10.1016/j.antiviral.2024.106017

Yijie Tang , Mingzhu Xu , Cong Wang , Min Wu , Lyuyin Hu , Jin Li , Wei Lu , Ye Zheng , Min Zhang , Xizi Jiang , Chuanwu Zhu , Jennifer Audsley , Pisit Tangkijvanich , Anchalee Avihingsanon , Shu Song , Shuangzhe Liu , Sharon R. Lewin , Jacob George , Mark W. Douglas , Yun Ling , Xiaonan Zhang

{"title":"Circulating capsid-antibody-complexes (CACs) drive intrahepatic complement deposition and inform subclinical liver inflammation in chronic hepatitis B","authors":"Yijie Tang , Mingzhu Xu , Cong Wang , Min Wu , Lyuyin Hu , Jin Li , Wei Lu , Ye Zheng , Min Zhang , Xizi Jiang , Chuanwu Zhu , Jennifer Audsley , Pisit Tangkijvanich , Anchalee Avihingsanon , Shu Song , Shuangzhe Liu , Sharon R. Lewin , Jacob George , Mark W. Douglas , Yun Ling , Xiaonan Zhang","doi":"10.1016/j.antiviral.2024.106017","DOIUrl":"10.1016/j.antiviral.2024.106017","url":null,"abstract":"<div><div>Chronic infection with Hepatitis B Virus (HBV) often results in a dysfunctional virus-specific T cell response hampering viral clearance. Paradoxically, intrahepatic inflammatory responses that contribute more to liver histopathology than to viral suppression are commonly observed, which are widely believed to be cell mediated. The involvement of humoral immunity in this process however is not well documented. To investigate the possible roles of HBV Capsid-Antibody Complexes (CACs) in eliciting chronic liver inflammation, we developed a novel microplate-based assay for the quantification of CACs in serum. The CACs assay showed high sensitivity and specificity with its readout closely correlating with the molecular features of CACs. A cross-sectional study on untreated chronic hepatitis B (CHB) patients showed a 77% positive rate for CACs with significant association with alanine transaminase (ALT), intrahepatic inflammation, and complement deposition, suggestive of its functional role in hepatic injury. Multiple staining of complement activation fragment C4d with major leukocyte and myofibroblast markers revealed an intertwined picture in periportal area with a morphology reminiscent of “piecemeal necrosis”. In a pooled cohort with ALT levels lower than 40 IU/ml, CACs alone revealed subclinical liver inflammation. We provide definitive evidence for a causative role for CACs in complement-mediated intrahepatic immunopathology, an additional mechanism contributing to liver damage in CHB. Assessment of CACs in serum complements current clinical markers for assessing CHB associated inflammation.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 106017"},"PeriodicalIF":4.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432764","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

Design and biological evaluation of candidate drugs against zoonotic porcine deltacoronavirus (PDCoV) 针对人畜共患猪三角花叶病毒（PDCoV）的候选药物的设计和生物学评价

IF 4.5 2区医学

Antiviral research Pub Date : 2024-10-10 DOI: 10.1016/j.antiviral.2024.106019

Junwei Zhou , Peng Sun , Yuanqing Wang , Yuting Shi , Chaoqun Chen , Wenwen Xiao , Runhui Qiu , Ting Cheng , Liurong Fang , Shaobo Xiao

{"title":"Design and biological evaluation of candidate drugs against zoonotic porcine deltacoronavirus (PDCoV)","authors":"Junwei Zhou , Peng Sun , Yuanqing Wang , Yuting Shi , Chaoqun Chen , Wenwen Xiao , Runhui Qiu , Ting Cheng , Liurong Fang , Shaobo Xiao","doi":"10.1016/j.antiviral.2024.106019","DOIUrl":"10.1016/j.antiviral.2024.106019","url":null,"abstract":"<div><div>Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus with zoonotic potential. PDCoV spillovers were recently detected in Haitian children with acute undifferentiated febrile illness, underscoring the urgent need to develop anti-PDCoV therapeutics. Coronavirus 3C-like protease (CoV 3CL<sup>pro</sup>) is essential for viral replication, and therefore provides an attractive target for drugs directed against CoV. Here, we initially evaluated the anti-PDCoV effect of Nirmatrelvir (PF-07321332), an FDA-approved anti-SARS-CoV-2 drug targeting viral 3CL<sup>pro</sup>. Regrettably, a very limited anti-PDCoV effect was achieved. By analyzing the binding modes of Nirmatrelvir with PDCoV 3CL<sup>pro</sup> and SARS-CoV-2 3CL<sup>pro</sup>, we demonstrated that the S2 pocket of 3CL<sup>pro</sup> is the primary factor underlying the differential inhibitory potency of Nirmatrelvir against different CoV 3CL<sup>pro</sup>s. Based on the specific characteristics of the S2 pocket of PDCoV 3CL<sup>pro</sup>, four derivatives of Nirmatrelvir (compounds T1–T4) with substituted P2 moieties were synthesized. Compound T1, with an isobutyl at the P2 site, displayed improved anti-PDCoV activity <em>in</em> <em>vitro</em> (cell infection model) and <em>in</em> <em>vivo</em> (embryonated chicken egg infection model), and therefore is a potential candidate drug to combat PDCoV. Together, our results identify the substrate-binding mode and substrate specificity of PDCoV 3CL<sup>pro</sup>, providing insight into the optimization of Nirmatrelvir as an antiviral therapeutic agent against PDCoV.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 106019"},"PeriodicalIF":4.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432763","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

Inhibitory peptides derived from Hepatitis C virus NS5A for reducing clinical symptoms of dengue virus infection 从丙型肝炎病毒 NS5A 提取的抑制肽用于减轻登革热病毒感染的临床症状。

IF 4.5 2区医学

Antiviral research Pub Date : 2024-10-09 DOI: 10.1016/j.antiviral.2024.106018

Younghoon Lee , Minjun Seo , Suk-hyun Yun , Minyeong Yu , Hyo Jin Kim , Hye Won Cho , Hee Won Byeon , Seong Ok Park , Erdenebileg Uyangaa , Hyunjin Jeon , Minhyeong Lee , Young Do Kwon , Seong Kug Eo

{"title":"Inhibitory peptides derived from Hepatitis C virus NS5A for reducing clinical symptoms of dengue virus infection","authors":"Younghoon Lee , Minjun Seo , Suk-hyun Yun , Minyeong Yu , Hyo Jin Kim , Hye Won Cho , Hee Won Byeon , Seong Ok Park , Erdenebileg Uyangaa , Hyunjin Jeon , Minhyeong Lee , Young Do Kwon , Seong Kug Eo","doi":"10.1016/j.antiviral.2024.106018","DOIUrl":"10.1016/j.antiviral.2024.106018","url":null,"abstract":"<div><div>Lethal Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) caused by Dengue virus (DENV) infection necessitate the development of effective treatments. Peptides derived from the N-terminal amphipathic α-helix of hepatitis C virus (HCV) NS5A exhibit antiviral activity by disrupting liposomes with high curvatures, such as virus envelopes. This study engineered five peptides from HCV genotype 3a NS5A N-terminal α-helix and screened them for neutralizing efficacy against three DENV serotypes. Two peptides, 3a 3/20 and DS-05, showed superior therapeutic efficacy against DENV and were further evaluated in treating DHF/DSS induced by mouse-adapted DENV infection. Administration of 3a 3/20 and DS-05 post-infection significantly improved mortality and weight loss associated with DHF/DSS in AG6 mice. These peptides reduced viral load in internal organs and viremia to levels comparable with the positive control drug, JNJ-A07, a DENV NS3-NS4B inhibitor. Additionally, they attenuated the cytokine storm in the blood and expression of inflammatory cytokines in internal organ tissues, ameliorating liver and kidney dysfunction after DENV infection. Histopathological analysis revealed significant suppression of damages in internal organs. These findings suggest that the 3a 3/20 and DS-05 peptides improve clinical symptoms of DHF/DSS induced by DENV infection, indicating their potential for clinical application.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 106018"},"PeriodicalIF":4.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399213","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

Comprehensive Herpesviruses Antiviral drug Resistance Mutation Database (CHARMD) 疱疹病毒抗病毒药物耐药性突变综合数据库（CHARMD）。

IF 4.5 2区医学

Antiviral research Pub Date : 2024-09-28 DOI: 10.1016/j.antiviral.2024.106016

Valentin Tilloy , Daniel Díaz-González , Lisa Laplace , Emilien Bisserier , Sunwen Chou , William D. Rawlinson , Guy Boivin , Fausto Baldanti , Tiziana Lazzarotto , Graciela Andrei , Hans H. Hirsch , María Ángeles Marcos , Detlef Michel , Sébastien Hantz , Sophie Alain

{"title":"Comprehensive Herpesviruses Antiviral drug Resistance Mutation Database (CHARMD)","authors":"Valentin Tilloy , Daniel Díaz-González , Lisa Laplace , Emilien Bisserier , Sunwen Chou , William D. Rawlinson , Guy Boivin , Fausto Baldanti , Tiziana Lazzarotto , Graciela Andrei , Hans H. Hirsch , María Ángeles Marcos , Detlef Michel , Sébastien Hantz , Sophie Alain","doi":"10.1016/j.antiviral.2024.106016","DOIUrl":"10.1016/j.antiviral.2024.106016","url":null,"abstract":"<div><div>A comprehensive and accessible Herpesvirus drug resistance database was designed to serve as an international reference for diagnosis and clinical studies. This database available at <span><span>https://www.unilim.fr/cnr-herpesvirus/outils/codexmv/</span><svg><path></path></svg></span>includes both resistance-related mutations and natural polymorphisms. Initially designed for human cytomegalovirus, it will be expanded to include herpes simplex and varicella-zoster viruses. Newly published mutations and new mutations reported by users or collaborating expert laboratories will be reviewed by an international committee of reference laboratories before inclusion in the database. Coupled with the Herpesvirus Sequence Analysis tool (HSA) mutation reports from NGS or Sanger sequences, it will be an open source for researchers in the field of Herpesviruses. We hope to fill this unmet need for the development and standardization of resistance genotyping.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 106016"},"PeriodicalIF":4.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340059","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

Functional comparison of Fc-engineering strategies to improve anti-HIV-1 antibody effector functions 改善抗 HIV-1 抗体效应器功能的 Fc 工程策略的功能比较。

IF 4.5 2区医学

Antiviral research Pub Date : 2024-09-27 DOI: 10.1016/j.antiviral.2024.106015

Angela I. Schriek , David Falck , Manfred Wuhrer , Neeltje A. Kootstra , Marit J. van Gils , Steven W. de Taeye

{"title":"Functional comparison of Fc-engineering strategies to improve anti-HIV-1 antibody effector functions","authors":"Angela I. Schriek , David Falck , Manfred Wuhrer , Neeltje A. Kootstra , Marit J. van Gils , Steven W. de Taeye","doi":"10.1016/j.antiviral.2024.106015","DOIUrl":"10.1016/j.antiviral.2024.106015","url":null,"abstract":"<div><div>Substantial reduction of the intact proviral reservoir is essential towards HIV-1 cure. <em>In vivo</em> administration of broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) trimer can decrease the viral reservoir, through Fc-mediated killing of infected cells. In this study, we compared three commonly used antibody engineering strategies to enhance Fc-mediated effector functions: (i) glyco-engineering, (ii) protein engineering, and (iii) subclass/hinge modifications in a panel of anti-HIV-1 antibodies. We found that antibody-dependent cellular phagocytosis (ADCP) was improved by elongating the hinge domain and switching to an IgG3 constant domain. In addition, potent NK cell activation and ADCC activity was observed for afucosylated antibodies and antibodies bearing the GASDALIE mutations. The combination of these engineering strategies further increased NK cell activation and induced antibody dependent cytotoxicity (ADCC) of infected cells at low antibody concentrations. The bNAb N6 was most effective at killing HIV-1 infected cells, likely due to its high affinity and optimal angle of approach. Overall, the findings of this study are applicable to other antibody formats, and can aid the development of effective immunotherapies and antibody-based treatments for HIV-1 cure strategies.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"231 ","pages":"Article 106015"},"PeriodicalIF":4.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340061","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