Antiviral research最新文献_第9页

Pralatrexate effectively inhibits the replication of monkeypox virus in vitro and in vivo 普拉特雷酯在体外和体内均能有效抑制猴痘病毒的复制。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-09-01 Epub Date: 2025-07-11 DOI: 10.1016/j.antiviral.2025.106232

Jianshu Li , Siyu Li , Chaode Gu , Shaowen Shi , Xiao Li , Zhendong Guo , Zongzheng Zhao , Miao He , Zhiwei Wu

引用次数: 0

Assessment of significant hepatic damage in young patients with chronic hepatitis B to initiate the antiviral treatment: The APLB score 评估年轻慢性乙型肝炎患者开始抗病毒治疗的显著肝损害：APLB评分

IF 4.5 2区医学

Antiviral research Pub Date : 2025-09-01 Epub Date: 2025-07-05 DOI: 10.1016/j.antiviral.2025.106234

Yi-Fan Guo , Yihui Rong , Yan-Ping Chen , Song Yang , Guangde Zhou , Xiao-Xia Niu , Xiao-Huan Wu , Yue-Ran Liu , Wen-Jing Zhang , Le Li , Yan Liu , Wen-Chang Wang , Xu-Yang Li , Chun-Yan Wang , Wucai Yang , Chang Guo , Lin Tan , Fu-Sheng Wang , Dong Ji

{"title":"Assessment of significant hepatic damage in young patients with chronic hepatitis B to initiate the antiviral treatment: The APLB score","authors":"Yi-Fan Guo , Yihui Rong , Yan-Ping Chen , Song Yang , Guangde Zhou , Xiao-Xia Niu , Xiao-Huan Wu , Yue-Ran Liu , Wen-Jing Zhang , Le Li , Yan Liu , Wen-Chang Wang , Xu-Yang Li , Chun-Yan Wang , Wucai Yang , Chang Guo , Lin Tan , Fu-Sheng Wang , Dong Ji","doi":"10.1016/j.antiviral.2025.106234","DOIUrl":"10.1016/j.antiviral.2025.106234","url":null,"abstract":"<div><div>Whether patients aged ≤30 years with chronic hepatitis B (CHB) and normal alanine transaminase (ALT) levels (<40 U/L) should receive antiviral therapy is controversial. In this study, we aimed to identify high-risk factors of significant hepatic damage (SHD) and established a scoring system to guide the decision to administer antiviral treatment. Eligible patients who underwent a liver biopsy were retrospectively screened and randomly assigned to either a training or validation set. Hepatic fibrosis (S0-4) and inflammation (G0-4) were assessed using the Scheuer scoring system. The independent risk factors associated with SHD (≥G2/S2) were identified using univariable and multivariable logistic regression analyses, and a new scoring system based on these factors was established. Among the 883 enrolled patients, 548 (62.1 %) were male, and 250 (28.5 %) presented with SHD. ALT, platelet count, HBV DNA, and liver stiffness measurement were identified as independent risk factors. A new scoring model based on these factors, named APLB, was developed. The area under the curve of APLB was 0.731 (95 % confidence interval, 0.695–0.764), which was significantly higher than those of the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. An APLB score <6 points ruled out SHD with 80.2 % sensitivity, while scores >12 points diagnosed SHD with 97.5 % specificity. In conclusion, the APLB scoring model demonstrated superior diagnostic performance compared with the APRI and the FIB-4 index, and it has the potential to guide the decision to initiate antiviral therapy in this patient group.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106234"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572844","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

Generation of a panel of mutants that are resistant to standard of care therapies in a clinically relevant strain of human cytomegalovirus for drug resistance profiling 在临床相关的人巨细胞病毒毒株中产生对标准护理疗法耐药的一组突变体，以进行耐药性分析

IF 4.5 2区医学

Antiviral research Pub Date : 2025-09-01 Epub Date: 2025-07-11 DOI: 10.1016/j.antiviral.2025.106237

Meghan F. Carter, Kassidy Knight, Yetunde Kayode, Eain A. Murphy

{"title":"Generation of a panel of mutants that are resistant to standard of care therapies in a clinically relevant strain of human cytomegalovirus for drug resistance profiling","authors":"Meghan F. Carter, Kassidy Knight, Yetunde Kayode, Eain A. Murphy","doi":"10.1016/j.antiviral.2025.106237","DOIUrl":"10.1016/j.antiviral.2025.106237","url":null,"abstract":"<div><div>Infection with human cytomegalovirus (HCMV) can result in a significant disease burden within the immunosuppressed and immunocompromised patient populations. Current standard of care (SOC) relies on direct-acting antivirals which target a limited group of viral proteins including the viral polymerase (UL54), terminase (UL56), and protein kinase (UL97). Incomplete inhibition of virally encoded proteins result in a selective pressure towards the generation of “breakthrough” drug resistant variants. One limitation in evaluating novel antivirals is the difficulty in profiling their antiviral activity against variants resistant to current SOC interventions, as these resistant variants have arisen in different genetic backgrounds with distinct replication kinetics and yields.</div><div>To limit strain variation we generated a targeted mutant panel of viruses in a bacterial artificial chromosome (BAC) derived clinically relevant laboratory strain of HCMV, TB40e, that expresses the fluorescent proteins mCherry upon viral entry and eGFP at times after viral DNA replication. This unique construct allows for the monitoring of viral entry and viral DNA replication independently. This panel consists of WT and seven mutant viruses harboring mutations that confer resistance to ganciclovir, maribavir, cidofovir, and letermovir. In addition, we characterized a host-targeted sirtuin 2 deacetylase (Sirt2) inhibitor, FLS-359, against the SOC resistant variants. We observed that mutant viruses demonstrated increased EC<sub>50</sub> concentrations for SOC inhibition, and that host directed FLS-359 demonstrated broad-spectrum antiviral activity against known SOC drug-resistant mutants. This panel represents a much-needed comparatively innovative platform for screening the efficacy of new direct-acting antivirals and host-directed antivirals against HCMV variants refractive to therapeutic interventions.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106237"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623823","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

Exploiting host kinases to combat dengue virus infection and disease 利用宿主激酶对抗登革病毒感染和疾病。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-09-01 Epub Date: 2025-05-08 DOI: 10.1016/j.antiviral.2025.106172

Natasha M. Bourgeois , Ling Wei , Alexis Kaushansky , John D. Aitchison

引用次数: 0

Meeting report: 38th international conference on antiviral research in Las Vegas, United States of America, March 17–21, 2025 会议报告：第38届国际抗病毒研究会议将于2025年3月17日至21日在美国拉斯维加斯举行。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-09-01 Epub Date: 2025-07-03 DOI: 10.1016/j.antiviral.2025.106222

Robert Jordan , Nancie M. Archin , Valeria Cagno , Joy Y. Feng , Haitao Guo , Lara J. Herrero , Zlatko Janeba , Nicholas A. Meanwell , Jennifer Moffat , Johan Neyts , Joana Rocha-Pereira , Kathie L. Seley-Radtke , Timothy P. Sheahan , Jessica R. Spengler , Stephen R. Welch , Xuping Xie , Hovakim Zakaryan , Luis M. Schang , David Durantel

{"title":"Meeting report: 38th international conference on antiviral research in Las Vegas, United States of America, March 17–21, 2025","authors":"Robert Jordan , Nancie M. Archin , Valeria Cagno , Joy Y. Feng , Haitao Guo , Lara J. Herrero , Zlatko Janeba , Nicholas A. Meanwell , Jennifer Moffat , Johan Neyts , Joana Rocha-Pereira , Kathie L. Seley-Radtke , Timothy P. Sheahan , Jessica R. Spengler , Stephen R. Welch , Xuping Xie , Hovakim Zakaryan , Luis M. Schang , David Durantel","doi":"10.1016/j.antiviral.2025.106222","DOIUrl":"10.1016/j.antiviral.2025.106222","url":null,"abstract":"<div><div>The 38th International Conference on Antiviral Research (ICAR), sponsored by the International Society for Antiviral Research (ISAR), took place March 17–21, 2025 in Las Vegas, Nevada, USA. The annual meeting brought together leading scientists from across academia, industry, and government to present the latest advances in antiviral research. Topics included discovery and development of novel antiviral agents, innovative therapeutic approaches, vaccine technologies, host-targeted strategies, and responses to emerging and re-emerging viral threats. ICAR 2025 featured keynote talks, short oral presentations, poster sessions and special sessions to encourage discussions between attendees and foster interdisciplinary collaboration. Several events were held to support the next generation of antiviral researchers, including dedicated sessions and networking opportunities focused on mentorship and career development for students, postdoctoral fellows, and early-career scientists. Importantly, ISAR continues to serve as a cornerstone for international collaboration and innovation in antiviral science, and the society is eager to continue these efforts at the 39th ICAR, to be held in Prague, Czech Republic, from April 27–May 1, 2026.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106222"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144566944","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

Effect of antivirals on clinical and lab-adapted human cytomegalovirus strains using induced pluripotent stem cell-derived human neural models 利用诱导多能干细胞衍生的人神经模型，抗病毒药物对临床和实验室适应的人巨细胞病毒株的影响。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-09-01 Epub Date: 2025-07-05 DOI: 10.1016/j.antiviral.2025.106233

Lance A Mulder , Renata Vieira da Sá , Joep Korsten , Eline Freeze , Amber J. Schotting , Gerrit Koen , Richard Molenkamp , Jeroen Van Kampen , Marion Cornelissen , Fokla Zorgdrager , Katja C Wolthers , Dasja Pajkrt , Adithya Sridhar , Carlemi Calitz

{"title":"Effect of antivirals on clinical and lab-adapted human cytomegalovirus strains using induced pluripotent stem cell-derived human neural models","authors":"Lance A Mulder , Renata Vieira da Sá , Joep Korsten , Eline Freeze , Amber J. Schotting , Gerrit Koen , Richard Molenkamp , Jeroen Van Kampen , Marion Cornelissen , Fokla Zorgdrager , Katja C Wolthers , Dasja Pajkrt , Adithya Sridhar , Carlemi Calitz","doi":"10.1016/j.antiviral.2025.106233","DOIUrl":"10.1016/j.antiviral.2025.106233","url":null,"abstract":"<div><div>Human cytomegalovirus (CMV) infections can cause severe neurological complications, particularly in newborns and immunocompromised patients. Children affected with congenital CMV infection may develop long-term neurological damage and intellectual disabilities. Currently, postnatal antiviral therapies are limited and there are no prenatal options available. Research on antivirals against congenital CMV infections is, at least partly, restricted due to the lack of physiologically relevant models and the use of lab-adapted CMV strains with limited clinical relevance. In this study, we evaluated the toxicity and antiviral efficacy of three FDA-approved anti-CMV drugs against two CMV strains, a clinical and a lab-adapted strain, using two human induced pluripotent stem cell (iPSC-)derived central nervous system models, <em>viz.</em> neural progenitor cells (NPCs) and dorsal forebrain regionalized neural organoids (RNOs). We found iPSC line-dependent differences in antiviral toxicity. We observed that antiviral treatment restored NPCs and RNOs gene expression after CMV infection and reduced CMV copy numbers. Infection of NPCs and RNOs with the clinical CMV strain, but not with the lab-adapted strain, led to an impaired expression of cortical development markers. Our findings highlight the value of using physiologically relevant human models and clinical CMV strains to understand the neuropathogenesis of congenital CMV and to test therapeutic strategies.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106233"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574740","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

Mammalian-targeted antiviral peptide reduces dengue virus type 1 infection in Aedes aegypti 哺乳动物靶向抗病毒肽可减少埃及伊蚊中1型登革热病毒感染

IF 4.5 2区医学

Antiviral research Pub Date : 2025-09-01 Epub Date: 2025-07-21 DOI: 10.1016/j.antiviral.2025.106241

Danya Medina-Carrasco , Glay Chinea Santiago , Hilda Elisa Garay Pérez , Gladys Gutiérrez-Bugallo , Luis Gabriel González-Lodeiro , Anubis Vega-Rúa , Vivian Huerta Galindo

{"title":"Mammalian-targeted antiviral peptide reduces dengue virus type 1 infection in Aedes aegypti","authors":"Danya Medina-Carrasco , Glay Chinea Santiago , Hilda Elisa Garay Pérez , Gladys Gutiérrez-Bugallo , Luis Gabriel González-Lodeiro , Anubis Vega-Rúa , Vivian Huerta Galindo","doi":"10.1016/j.antiviral.2025.106241","DOIUrl":"10.1016/j.antiviral.2025.106241","url":null,"abstract":"<div><div>Dengue virus is the most important arbovirus for public health worldwide. <em>Aedes aegypti</em> is the DENV primary vector and acquires the virus during blood meal from a viremic human. BCN0941 is a structure-based designed antiviral peptide that inhibits early stages of DENV infection in mammalian cells [WO2015131858A2]. Studies of structure-activity relationship indicate that the molecular target of the antiviral activity of BCN0941 is the Low-density lipoprotein receptor related protein-1 (LRP1), an evolutionary conserved receptor that we have identified as putative DENV receptor in mammalian cells. In this work, we evaluated the antiviral activity of BCN0941 peptide against DENV serotype 1 in mosquito cells. <em>In vitro</em> assays were performed in cell lines C6/36 (<em>Aedes albopictus</em>) and Aag2 (<em>Aedes aegypti</em>)<em>.</em> The antiviral activity <em>in vivo</em> in a metapopulation of field-collected <em>A. aegypti</em> mosquitoes was also evaluated. BCN0941 peptide exhibited the capacity to decrease viral infection in both experimental set up, <em>in vivo</em> and <em>in vitro</em>, up to a 50 % and 60 % of the treatment controls respectively, as determined by immunofluorescence. BCN0941 may be an effective DENV transmission-blocking drug due to its dual action in decreasing the viral load in infected people and the mosquito vector.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106241"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678857","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

Single-dose injection of human neutralizing antibody against ZIKV preserves male fertility and protects against lethal infection 单剂量注射人抗寨卡病毒中和抗体保护男性生育能力和预防致命感染。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-09-01 Epub Date: 2025-07-22 DOI: 10.1016/j.antiviral.2025.106240

Hao Zhang , Ziyang Sheng , Feiyang Xue , Han Wang , Na Gao , Shiqi He , Yuetong Li , Dongying Fan , Peigang Wang , Lei Yu , Jing An

{"title":"Single-dose injection of human neutralizing antibody against ZIKV preserves male fertility and protects against lethal infection","authors":"Hao Zhang , Ziyang Sheng , Feiyang Xue , Han Wang , Na Gao , Shiqi He , Yuetong Li , Dongying Fan , Peigang Wang , Lei Yu , Jing An","doi":"10.1016/j.antiviral.2025.106240","DOIUrl":"10.1016/j.antiviral.2025.106240","url":null,"abstract":"<div><div>Zika virus (ZIKV) is a mosquito-transmitted flavivirus. Unlike other flavivirus members, ZIKV has a distinct tropism for the reproductive system. Previous studies have demonstrated that ZIKV has adverse impacts on the male reproductive system, particularly in testis and epididymis. However, no specific prophylactic and therapeutic agents are available against ZIKV till now. A human monoclonal antibody, 2B10, has been shown to be protective against microcephaly. Here, we intraperitoneally administered a single injection of 2B10 after ZIKV infection to explore its therapeutic potential on viral damage in testis and epididymis in both IFN-α/β and IFN-γ receptor-deficient (AG6) mouse and IFN-α/β receptor-deficient (A6) mouse models. The results showed that 2B10 significantly decreased the viremia and viral loads in organs in two types of male mice, markedly mitigated ZIKV-induced histo-morphologic disruption and inflammatory infiltration and maintained hormone levels. The integrity of tight junctions in the testis and epididymis was also maintained at normal levels by 2B10 administration. In long-term observation in ZIKV-infected A6 mice, 2B10 could confer effective protection of male fertility. In the AG6 model, 2B10 fully protected mice from lethal challenge. These results suggested that 2B10 provides effective protection in post-exposure therapy for ZIKV infection in mice. Since 2B10 is a human antibody, it might be a promising intervention candidate for maintaining male reproductive health during ZIKV infection in the endemic area.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106240"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697463","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

SARS-CoV-2 neutralization and protection of hamsters via nasal administration of a humanized neutralizing antibody 通过鼻给药人源化中和抗体对仓鼠的SARS-CoV-2中和和保护作用。

IF 4.5 2区医学

Antiviral research Pub Date : 2025-09-01 Epub Date: 2025-07-09 DOI: 10.1016/j.antiviral.2025.106235

Mikhail Lebedin , Nikolai Petrovsky , Kairat Tabynov , Kaissar Tabynov , Yuri Lebedin

{"title":"SARS-CoV-2 neutralization and protection of hamsters via nasal administration of a humanized neutralizing antibody","authors":"Mikhail Lebedin , Nikolai Petrovsky , Kairat Tabynov , Kaissar Tabynov , Yuri Lebedin","doi":"10.1016/j.antiviral.2025.106235","DOIUrl":"10.1016/j.antiviral.2025.106235","url":null,"abstract":"<div><div>Monoclonal antibodies are widely used for the treatment of infectious human diseases, including COVID-19. Since the start of the pandemic, eight monoclonal antibodies against SARS-CoV-2 were granted emergency use authorization. The high mutation rate of the SARS-CoV-2 virus has led to the emergence of highly transmissible variants that can evade vaccine-induced immunity. In this study, we generated a panel of murine monoclonal antibodies (mAb) to identify a subset that broadly neutralized SARS-CoV-2 variants and explored whether mucosal administration of such antibodies could protect against infection. Intranasal delivery of XR10, the most promising murine mAb, protected hamsters against infection by Delta variant. We next humanized XR10 mAb using a combination of CDR-grafting and Vernier zones preservation approaches (CRVZ) to create a panel of humanized XR10 variants. We ranked the variants based on their spike binding ability and virus neutralization. Of these, XR10v48 demonstrated the best ability to neutralize SARS-CoV-2 variants and was protective in hamsters when given as a single 50 μg/kg intranasal dose at the time of viral challenge. XR10v48 featured 34 key amino acid residues retained from the murine progenitor. With SARS-CoV-2 escape mutants continuing to emerge this work highlights a potential workflow to generate humanized broadly cross-neutralizing mAb for potential use as a nasal spray for SARS-CoV-2 prophylaxis.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106235"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616059","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

Discovery of broad-spectrum antivirals targeting viral proteases using in silico structural modeling and cellular analysis 利用硅结构建模和细胞分析发现针对病毒蛋白酶的广谱抗病毒药物

IF 4 2区医学

Antiviral research Pub Date : 2025-09-01 Epub Date: 2025-07-29 DOI: 10.1016/j.antiviral.2025.106245

Dharmeshkumar Patel , Ramyani De , Niloufar Azadi , Sujin Lee , Savannah Shooter , Sarah Amichai , Shaoman Zhou , Danielle Monroe , Cameron Mahanke , Tamara R. McBrayer , Michael Muczynski , Abdullah Al-Homoudi , Joseph Engel , Yury A. Bochkov , James E. Gern , Ladislau C. Kovari , Franck Amblard , Raymond F. Schinazi

{"title":"Discovery of broad-spectrum antivirals targeting viral proteases using in silico structural modeling and cellular analysis","authors":"Dharmeshkumar Patel , Ramyani De , Niloufar Azadi , Sujin Lee , Savannah Shooter , Sarah Amichai , Shaoman Zhou , Danielle Monroe , Cameron Mahanke , Tamara R. McBrayer , Michael Muczynski , Abdullah Al-Homoudi , Joseph Engel , Yury A. Bochkov , James E. Gern , Ladislau C. Kovari , Franck Amblard , Raymond F. Schinazi","doi":"10.1016/j.antiviral.2025.106245","DOIUrl":"10.1016/j.antiviral.2025.106245","url":null,"abstract":"<div><div>The development of broad-spectrum antivirals is a high-priority goal to prevent future global outbreaks. Some antiviral agents developed for specific viral protein targets may exhibit broad-spectrum antiviral activity or provide helpful information for broad-spectrum drug development. In this study, we compared the sequence- and structure-based similarity of SARS-CoV-2 3CL<sup>pro</sup> with proteases from other viruses and identified 24 proteases with similar active-site structures. Our in-house lead molecules, NIP-22c and CIP-1 were reported as novel peptidomimetic, reversible covalent inhibitors of SARS-CoV-2 3CL<sup>pro</sup> with nanomolar potency. Molecular docking of NIP-22c, CIP-1 and nirmatrelvir were performed with structurally similar proteases of different viruses, norovirus, enterovirus and rhinovirus. The predictions were validated with in vitro enzymatic and cell-based assays. As predicted, NIP-22c and CIP-1 showed broad-spectrum antiviral activity with EC<sub>50</sub> values in the nanomolar range against SARS-CoV-2, norovirus, enterovirus and rhinovirus by targeting 3CL/3C<sup>pro</sup>. In contrast, nirmatrelvir did not show activity up to 10 μM against all three viruses and the mechanism of inactivity of nirmatrelvir was hypothesized through binding pocket analysis using molecular dynamics simulations.</div></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"241 ","pages":"Article 106245"},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739546","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