Antiviral research最新文献_第10页

Development of nanoparticle vaccines utilizing designed Fc-binding homo-oligomers and RBD-Fc of SARS-CoV-2 利用设计的 SARS-CoV-2 Fc 结合同源异构体和 RBD-Fc 开发纳米颗粒疫苗。

IF 7.6 2区医学

Antiviral research Pub Date : 2024-05-21 DOI: 10.1016/j.antiviral.2024.105917

Yucai Liang , Weiling Xiao , Yuan Peng , Shengshuo Zhang , Jinhua Dong , Jun Zhao , Yuhui Wang , Mengtao Zhang , Zhijun Liu , Bowen Yu

{"title":"Development of nanoparticle vaccines utilizing designed Fc-binding homo-oligomers and RBD-Fc of SARS-CoV-2","authors":"Yucai Liang , Weiling Xiao , Yuan Peng , Shengshuo Zhang , Jinhua Dong , Jun Zhao , Yuhui Wang , Mengtao Zhang , Zhijun Liu , Bowen Yu","doi":"10.1016/j.antiviral.2024.105917","DOIUrl":"10.1016/j.antiviral.2024.105917","url":null,"abstract":"<div><p>The Fc-fused receptor binding domain (RBD-Fc) vaccine for SARS-CoV-2 has garnered significant attention for its capacity to provide effective and specific immune protection. However, its immunogenicity is limited, highlighting the need for improvement in clinical application. Nanoparticle delivery has been shown to be an effective method for enhancing antigen immunogenicity. In this study, we developed bivalent nanoparticle recombinant protein vaccines by assembling the RBD-Fc of SARS-CoV-2 and Fc-binding homo-oligomers o42.1 and i52.3 into octahedral and icosahedral nanoparticles. The formation of RBD-Fc nanoparticles was confirmed through structural characterization and cell binding experiments. Compared to RBD-Fc dimers, the nanoparticle vaccines induced more potent neutralizing antibodies (nAb) and stronger cellular immune responses. Therefore, using bivalent nanoparticle vaccines based on RBD-Fc presents a promising vaccination strategy against SARS-CoV-2 and offers a universal approach for enhancing the immunogenicity of Fc fusion protein vaccines.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"227 ","pages":"Article 105917"},"PeriodicalIF":7.6,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086059","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

Structural biology of flavivirus NS1 protein and its antibody complexes 黄热病病毒 NS1 蛋白及其抗体复合物的结构生物学。

IF 7.6 2区医学

Antiviral research Pub Date : 2024-05-20 DOI: 10.1016/j.antiviral.2024.105915

Bing Liang Alvin Chew , Qi Pan , Hongli Hu , Dahai Luo

{"title":"Structural biology of flavivirus NS1 protein and its antibody complexes","authors":"Bing Liang Alvin Chew , Qi Pan , Hongli Hu , Dahai Luo","doi":"10.1016/j.antiviral.2024.105915","DOIUrl":"10.1016/j.antiviral.2024.105915","url":null,"abstract":"<div><p>The genus of flavivirus includes many mosquito-borne human pathogens, such as Zika (ZIKV) and the four serotypes of dengue (DENV1-4) viruses, that affect billions of people as evidenced by epidemics and endemicity in many countries and regions in the world. Among the 10 viral proteins encoded by the viral genome, the nonstructural protein 1 (NS1) is the only secreted protein and has been used as a diagnostic biomarker. NS1 has also been an attractive target for its biotherapeutic potential as a vaccine antigen. This review focuses on the recent advances in the structural landscape of the secreted NS1 (sNS1) and its complex with monoclonal antibodies (mAbs). NS1 forms an obligatory dimer, and upon secretion, it has been reported to be hexametric (trimeric dimers) that could dissociate and bind to the epithelial cell membrane. However, high-resolution structural information has been missing about the high-order oligomeric states of sNS1. Several cryoEM studies have since shown that DENV and ZIKV recombinant sNS1 (rsNS1) are in dynamic equilibrium of dimer-tetramer-hexamer states, with tetramer being the predominant form. It was recently revealed that infection-derived sNS1 (isNS1) forms a complex of the NS1 dimer partially embedded in a High-Density Lipoprotein (HDL) particle. Structures of NS1 in complexes with mAbs have also been reported which shed light on their protective roles during infection. The biological significance of the diversity of NS1 oligomeric states remains to be further studied, to inform future research on flaviviral pathogenesis and the development of therapeutics and vaccines. Given the polymorphism of flavivirus NS1 across sample types with variations in antigenicity, we propose a nomenclature to accurately define NS1 based on the localization and origin.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"227 ","pages":"Article 105915"},"PeriodicalIF":7.6,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166354224001244/pdfft?md5=5fb1baf095c37122806b74c688b6f5a7&pid=1-s2.0-S0166354224001244-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079953","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

JNJ-7184, a respiratory syncytial virus inhibitor targeting the connector domain of the viral polymerase JNJ-7184 是一种针对病毒聚合酶接头结构域的呼吸道合胞病毒抑制剂。

IF 7.6 2区医学

Antiviral research Pub Date : 2024-05-19 DOI: 10.1016/j.antiviral.2024.105907

Brecht Bonneux , Afzaal Shareef , Sergey Tcherniuk , Brandon Anson , Suzanne de Bruyn , Nick Verheyen , Kim Thys , Nádia Conceição-Neto , Marcia Van Ginderen , Leen Kwanten , Nina Ysebaert , Luc Vranckx , Elien Peeters , Ellen Lanckacker , Jack M. Gallup , Panchan Sitthicharoenchai , Sarhad Alnajjar , Mark R. Ackermann , Suraj Adhikary , Anusarka Bhaumik , Florence Herschke

{"title":"JNJ-7184, a respiratory syncytial virus inhibitor targeting the connector domain of the viral polymerase","authors":"Brecht Bonneux , Afzaal Shareef , Sergey Tcherniuk , Brandon Anson , Suzanne de Bruyn , Nick Verheyen , Kim Thys , Nádia Conceição-Neto , Marcia Van Ginderen , Leen Kwanten , Nina Ysebaert , Luc Vranckx , Elien Peeters , Ellen Lanckacker , Jack M. Gallup , Panchan Sitthicharoenchai , Sarhad Alnajjar , Mark R. Ackermann , Suraj Adhikary , Anusarka Bhaumik , Florence Herschke","doi":"10.1016/j.antiviral.2024.105907","DOIUrl":"10.1016/j.antiviral.2024.105907","url":null,"abstract":"<div><p>Respiratory syncytial virus (RSV) can cause pulmonary complications in infants, elderly and immunocompromised patients. While two vaccines and two prophylactic monoclonal antibodies are now available, treatment options are still needed. JNJ-7184 is a non-nucleoside inhibitor of the RSV-Large (L) polymerase, displaying potent inhibition of both RSV-A and -B strains. Resistance selection and hydrogen-deuterium exchange experiments suggest JNJ-7184 binds RSV-L in the connector domain. JNJ-7184 prevents RSV replication and transcription by inhibiting initiation or early elongation. JNJ-7184 is effective in air-liquid interface cultures and therapeutically in neonatal lambs, acting to drastically reverse the appearance of lung pathology.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"227 ","pages":"Article 105907"},"PeriodicalIF":7.6,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075095","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

Cytomegalovirus UL44 protein induces a potent T-cell immune response in mice 巨细胞病毒 UL44 蛋白可诱导小鼠产生强烈的 T 细胞免疫反应。

IF 7.6 2区医学

Antiviral research Pub Date : 2024-05-15 DOI: 10.1016/j.antiviral.2024.105914

Francisco J. Mancebo , Marcos Nuévalos , Jaanam Lalchandani , Antonio J. Martín Galiano , Mario Fernández-Ruiz , José María Aguado , Estéfani García-Ríos , Pilar Pérez-Romero

{"title":"Cytomegalovirus UL44 protein induces a potent T-cell immune response in mice","authors":"Francisco J. Mancebo , Marcos Nuévalos , Jaanam Lalchandani , Antonio J. Martín Galiano , Mario Fernández-Ruiz , José María Aguado , Estéfani García-Ríos , Pilar Pérez-Romero","doi":"10.1016/j.antiviral.2024.105914","DOIUrl":"10.1016/j.antiviral.2024.105914","url":null,"abstract":"<div><p>Due to the severity of CMV infection in immunocompromised individuals the development of a vaccine has been declared a priority. However, despite the efforts made there is no yet a vaccine available for clinical use. We designed an approach to identify new CMV antigens able to inducing a broad immune response that could be used in future vaccine formulations.</p><p>We have used serum samples from 28 kidney transplant recipients, with a previously acquired CMV-specific immune response to identify viral proteins that were recognized by the antibodies present in the patient serum samples by Western blot. A band of approximately 45 kDa, identified as UL44, was detected by most serum samples. UL44 immunogenicity was tested in BALB/c mice that received three doses of the UL44-pcDNA DNA vaccine. UL44 elicited both, a strong antibody response and CMV-specific cellular response. Using bioinformatic analysis we demonstrated that UL44 is a highly conserved protein and contains epitopes that are able to activate CD8 lymphocytes of the most common HLA alleles in the world population. We constructed a UL44 ORF deletion mutant virus that produced no viral progeny, suggesting that UL44 is an essential viral protein. In addition, other authors have demonstrated that UL44 is one of the most abundant viral proteins after infection and have suggested an essential role of UL44 in viral replication. Altogether, our data suggests that UL44 is a potent antigen, and favored by its abundance, it may be a good candidate to include in a vaccine formulation.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"227 ","pages":"Article 105914"},"PeriodicalIF":7.6,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956046","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

Three in one: An effective and universal vaccine expressing heterologous tandem RBD trimer by rabies virus vector protects mice against SARS-CoV-2 三合一：通过狂犬病毒载体表达异源串联 RBD 三聚体的有效通用疫苗可保护小鼠免受 SARS-CoV-2 的感染。

IF 7.6 2区医学

Antiviral research Pub Date : 2024-05-11 DOI: 10.1016/j.antiviral.2024.105905

Jingbo Huang , Weiqi Wang , Hailun Li , Yujie Bai , Yumeng Song , Cuicui Jiao , Hongli Jin , Pei Huang , Haili Zhang , Xianzhu Xia , Feihu Yan , Yuanyuan Li , Hualei Wang

{"title":"Three in one: An effective and universal vaccine expressing heterologous tandem RBD trimer by rabies virus vector protects mice against SARS-CoV-2","authors":"Jingbo Huang , Weiqi Wang , Hailun Li , Yujie Bai , Yumeng Song , Cuicui Jiao , Hongli Jin , Pei Huang , Haili Zhang , Xianzhu Xia , Feihu Yan , Yuanyuan Li , Hualei Wang","doi":"10.1016/j.antiviral.2024.105905","DOIUrl":"10.1016/j.antiviral.2024.105905","url":null,"abstract":"<div><p>The rapid emergence of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) variants, coupled with severe immune evasion and imprinting, has jeopardized the vaccine efficacy, necessitating urgent development of broad protective vaccines. Here, we propose a strategy employing recombinant rabies viruses (RABV) to create a universal SARS-CoV-2 vaccine expressing heterologous tandem receptor-binding domain (RBD) trimer from the SARS-CoV-2 Prototype, Delta, and Omicron strains (SRV-PDO). The results of mouse immunization indicated that SRV-PDO effectively induced cellular and humoral immune responses, and demonstrated higher immunogenicity and broader SARS-CoV-2 neutralization compared to the recombinant RABVs that only expressed RBD monomers. Moreover, SRV-PDO exhibited full protection against SARS-CoV-2 in the challenge assay. This study demonstrates that recombinant RABV expressing tandem RBD-heterotrimer as a multivalent immunogen could elicit a broad-spectrum immune response and potent protection against SARS-CoV-2, making it a promising candidate for future human or veterinary vaccines and offering a novel perspective in other vaccine design.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"227 ","pages":"Article 105905"},"PeriodicalIF":7.6,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915785","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 new compound, phomaherbarine A, induces cytolytic reactivation in epstein-barr virus-positive B cell lines 一种新化合物--磷脂酰巴比妥碱 A--可诱导 Epstein-Barr 病毒阳性 B 细胞系的细胞溶解再活化。

IF 7.6 2区医学

Antiviral research Pub Date : 2024-05-10 DOI: 10.1016/j.antiviral.2024.105906

So-Eun Bae , Jin Won Choi , Ji-Woon Hong , Hyeri Ku , Kyu-Young Sim , Gwang-Hoon Ko , Dae Sik Jang , Sang Hee Shim , Sung-Gyoo Park

{"title":"A new compound, phomaherbarine A, induces cytolytic reactivation in epstein-barr virus-positive B cell lines","authors":"So-Eun Bae , Jin Won Choi , Ji-Woon Hong , Hyeri Ku , Kyu-Young Sim , Gwang-Hoon Ko , Dae Sik Jang , Sang Hee Shim , Sung-Gyoo Park","doi":"10.1016/j.antiviral.2024.105906","DOIUrl":"10.1016/j.antiviral.2024.105906","url":null,"abstract":"<div><p>Epstein-Barr virus (EBV), the first virus found to induce cancer in humans, has been frequently detected in various types of B cell lymphomas. During its latent phase, EBV expresses a limited set of proteins crucial for its persistence. Induction of the lytic phase of EBV has shown promise in the treatment of EBV-associated malignancies. The present study assessed the ability of phomaherbarine A, a novel compound derived from the endophytic fungus <em>Phoma herbarum</em> DBE-M1, to stimulate lytic replication of EBV in B95-8 cells. Phomaherbarine A was found to efficiently initiate the expression of both early and late EBV lytic genes in B95-8 cells, with this initiation being further heightened by the addition of phorbol myristate acetate and sodium butyrate. Moreover, phomaherbarine A demonstrated notable cytotoxicity against the EBV-associated B cell lymphoma cell lines B95-8 and Raji. Mechanistically, phomaherbarine A induces apoptosis in these cells through the activation of caspase-3/7. When combined with ganciclovir, phomaherbarine A does not interfere with the reduction of viral replication by ganciclovir and sustains its apoptosis induction. In conclusion, these findings indicate that phomaherbarine A may be a promising candidate for therapeutic intervention in patients with EBV-associated B cell lymphomas.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"227 ","pages":"Article 105906"},"PeriodicalIF":7.6,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911358","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

Lectibodies as antivirals 作为抗病毒药物的抗体。

IF 7.6 2区医学

Antiviral research Pub Date : 2024-05-10 DOI: 10.1016/j.antiviral.2024.105901

Ian Carlosalberto Santisteban Celis , Nobuyuki Matoba

{"title":"Lectibodies as antivirals","authors":"Ian Carlosalberto Santisteban Celis , Nobuyuki Matoba","doi":"10.1016/j.antiviral.2024.105901","DOIUrl":"10.1016/j.antiviral.2024.105901","url":null,"abstract":"<div><p>Growing concerns regarding the emergence of highly transmissible viral diseases highlight the urgent need to expand the repertoire of antiviral therapeutics. For this reason, new strategies for neutralizing and inhibiting these viruses are necessary. A promising approach involves targeting the glycans present on the surfaces of enveloped viruses. Lectins, known for their ability to recognize specific carbohydrate molecules, offer the potential for glycan-targeted antiviral strategies. Indeed, numerous studies have reported the antiviral effects of various lectins of both endogenous and exogenous origins. However, many lectins in their natural forms, are not suitable for use as antiviral therapeutics due to toxicity, other unfavorable pharmacological effects, and/or unreliable manufacturing sources. Therefore, improvements are crucial for employing lectins as effective antiviral therapeutics. A novel approach to enhance lectins’ suitability as pharmaceuticals could be the generation of recombinant lectin-Fc fusion proteins, termed “lectibodies.” In this review, we discuss the scientific rationale behind lectin-based antiviral strategies and explore how lectibodies could facilitate the development of new antiviral therapeutics. We will also share our perspective on the potential of these molecules to transcend their potential use as antiviral agents.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"227 ","pages":"Article 105901"},"PeriodicalIF":7.6,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907849","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

New technologies in therapeutic antibody development: The next frontier for treating infectious diseases 治疗性抗体开发的新技术：治疗传染病的下一个前沿。

IF 7.6 2区医学

Antiviral research Pub Date : 2024-05-09 DOI: 10.1016/j.antiviral.2024.105902

Sheila M. Keating , Brett W. Higgins

{"title":"New technologies in therapeutic antibody development: The next frontier for treating infectious diseases","authors":"Sheila M. Keating , Brett W. Higgins","doi":"10.1016/j.antiviral.2024.105902","DOIUrl":"10.1016/j.antiviral.2024.105902","url":null,"abstract":"<div><p>Adaptive immunity to viral infections requires time to neutralize and clear viruses to resolve infection. Fast growing and pathogenic viruses are quickly established, are highly transmissible and cause significant disease burden making it difficult to mount effective responses, thereby prolonging infection. Antibody-based passive immunotherapies can provide initial protection during acute infection, assist in mounting an adaptive immune response, or provide protection for those who are immune suppressed or immune deficient. Historically, plasma-derived antibodies have demonstrated some success in treating diseases caused by viral pathogens; nonetheless, limitations in access to product and antibody titer reduce success of this treatment modality. Monoclonal antibodies (mAbs) have proven an effective alternative, as it is possible to manufacture highly potent and specific mAbs against viral targets on an industrial scale. As a result, innovative technologies to discover, engineer and manufacture specific and potent antibodies have become an essential part of the first line of treatment in pathogenic viral infections. However, a mAb targeting a specific epitope will allow escape variants to outgrow, causing new variant strains to become dominant and resistant to treatment with that mAb. Methods to mitigate escape have included combining mAbs into cocktails, creating bi-specific or antibody drug conjugates but these strategies have also been challenged by the potential development of escape mutations. New technologies in developing antibodies made as recombinant polyclonal drugs can integrate the strength of poly-specific antibody responses to prevent mutational escape, while also incorporating antibody engineering to prevent antibody dependent enhancement and direct adaptive immune responses.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"227 ","pages":"Article 105902"},"PeriodicalIF":7.6,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907853","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

SRX3177, a CDK4/6-PI3K-BET inhibitor, in combination with an RdRp inhibitor, Molnupiravir, or an entry inhibitor MU-UNMC-2, has potent antiviral activity against the Omicron variant of SARS-CoV-2 SRX3177 是一种 CDK4/6-PI3K-BET 抑制剂，与 RdRp 抑制剂 Molnupiravir 或入口抑制剂 MU-UNMC-2 联合使用，对 SARS-CoV-2 的 Omicron 变体具有很强的抗病毒活性。

IF 7.6 2区医学

Antiviral research Pub Date : 2024-05-08 DOI: 10.1016/j.antiviral.2024.105904

Kabita Pandey , Arpan Acharya , Dhananjaya Pal , Prashant Jain , Kamal Singh , Donald L. Durden , Tatiana G. Kutateladze , Aniruddha J. Deshpande , Siddappa N. Byrareddy

{"title":"SRX3177, a CDK4/6-PI3K-BET inhibitor, in combination with an RdRp inhibitor, Molnupiravir, or an entry inhibitor MU-UNMC-2, has potent antiviral activity against the Omicron variant of SARS-CoV-2","authors":"Kabita Pandey , Arpan Acharya , Dhananjaya Pal , Prashant Jain , Kamal Singh , Donald L. Durden , Tatiana G. Kutateladze , Aniruddha J. Deshpande , Siddappa N. Byrareddy","doi":"10.1016/j.antiviral.2024.105904","DOIUrl":"10.1016/j.antiviral.2024.105904","url":null,"abstract":"<div><p>Despite considerable progress in developing vaccines and antivirals to combat COVID-19, the rapid mutations of the SARS-CoV-2 genome have limited the durability and efficacy of the current vaccines and therapeutic interventions. Hence, it necessitates the development of novel therapeutic approaches or repurposing existing drugs that target either viral life cycle, host factors, or both. Here, we report that SRX3177, a potent triple-activity CDK4/6-PI3K-BET inhibitor, blocks replication of the SARS-CoV-2 Omicron variant with IC<sub>50</sub> values at sub-micromolar concentrations without any impact on the cell proliferation of Calu-3 cells at and below its IC<sub>50</sub> concentration. When SRX3177 is combined with EIDD-1931 (active moiety of a small-molecule prodrug Molnupiravir) or MU-UNMC-2 (a SARS-CoV-2 entry inhibitor) at a fixed doses matrix, a synergistic effect was observed, leading to the significant reduction in the dose of the individual compounds to achieve similar inhibition of SARS-CoV-2 replication. Herein, we report that the combination of SRX3177/MPV or SRX3177/UM-UNMC-2 has the potential for further development as a combinational therapy against SARS-CoV-2 and in any future outbreak of beta coronavirus.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"227 ","pages":"Article 105904"},"PeriodicalIF":7.6,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904062","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

Characterization of SARS-CoV-2 replication in human H1299/ACE2 cells: A versatile and practical infection model for antiviral research and beyond SARS-CoV-2 在人类 H1299/ACE2 细胞中复制的特征：一种用于抗病毒研究及其他领域的多功能实用感染模型。

IF 7.6 2区医学

Antiviral research Pub Date : 2024-05-07 DOI: 10.1016/j.antiviral.2024.105903

Clarisse Salgado-Benvindo , Ali Tas , Jessika C. Zevenhoven-Dobbe , Yvonne van der Meer , Igor A. Sidorov , Anouk A. Leijs , Patrick Wanningen , Anne T. Gelderloos , Puck B. van Kasteren , Eric J. Snijder , Martijn J. van Hemert

{"title":"Characterization of SARS-CoV-2 replication in human H1299/ACE2 cells: A versatile and practical infection model for antiviral research and beyond","authors":"Clarisse Salgado-Benvindo , Ali Tas , Jessika C. Zevenhoven-Dobbe , Yvonne van der Meer , Igor A. Sidorov , Anouk A. Leijs , Patrick Wanningen , Anne T. Gelderloos , Puck B. van Kasteren , Eric J. Snijder , Martijn J. van Hemert","doi":"10.1016/j.antiviral.2024.105903","DOIUrl":"10.1016/j.antiviral.2024.105903","url":null,"abstract":"<div><p>A range of cell culture infection models have been used to study SARS-CoV-2 and perform antiviral drug research. Commonly used African green monkey Vero, human lung-derived Calu-3 and ACE2+TMPRSS2-expressing A549 cells, each have their limitations. Here, we describe human ACE2-expressing H1299 lung cells as a more efficient and robust model for SARS-CoV-2 research. These cells are as easy to handle as Vero cells, support SARS-CoV-2 replication to high titers, display a functional innate immune response and are suitable for plaque assays, microscopy, the production of (genetically stable) virus stocks and antiviral assays. H1299/ACE2-based (CPE reduction) assays can be performed without adding a P-gP drug efflux pump inhibitor, which is often required in Vero-based assays. Moreover, H1299/ACE2 cells allowed us to perform CPE reduction assays with omicron variants that did not work in Vero-based assays. In summary, H1299/ACE2 cells are a versatile infection model to study SARS-CoV-2 replication in the context of antiviral drug development and virus-host interaction studies.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"227 ","pages":"Article 105903"},"PeriodicalIF":7.6,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166354224001128/pdfft?md5=92fc4a305322f2a32bfbc7a993302019&pid=1-s2.0-S0166354224001128-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896993","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