Antiviral research最新文献

{"title":"KDM5A/B contribute to HIV-1 latent infection and survival of HIV-1 infected cells","authors":"Tai-Wei Li ,&nbsp;Youngmin Park ,&nbsp;Emily G. Watters ,&nbsp;Xu Wang ,&nbsp;Dawei Zhou ,&nbsp;Guillaume N. Fiches ,&nbsp;Zhenyu Wu ,&nbsp;Andrew D. Badley ,&nbsp;Jonah B. Sacha ,&nbsp;Wen-Zhe Ho ,&nbsp;Netty G. Santoso ,&nbsp;Jun Qi ,&nbsp;Jian Zhu","doi":"10.1016/j.antiviral.2024.105947","DOIUrl":"10.1016/j.antiviral.2024.105947","url":null,"abstract":"<div><p>Combinational antiretroviral therapy (cART) suppresses human immunodeficiency virus type 1 (HIV-1) viral replication and pathogenesis in acquired immunodeficiency syndrome (AIDS) patients. However, HIV-1 remains in the latent stage of infection by suppressing viral transcription, which hinders an HIV-1 cure. One approach for an HIV-1 cure is the “shock and kill” strategy. The strategy focuses on reactivating latent HIV-1, inducing the viral cytopathic effect and facilitating the immune clearance for the elimination of latent HIV-1 reservoirs. Here, we reported that the H3K4 trimethylation (H3K4me3)-specific demethylase KDM5A/B play a role in suppressing HIV-1 Tat/LTR-mediated viral transcription in HIV-1 latent cells. Furthermore, we evaluated the potential of KDM5-specific inhibitor JQKD82 as an HIV-1 “shock and kill” agent. Our results showed that JQKD82 increases the H3K4me3 level at HIV-1 5’ LTR promoter regions, HIV-1 reactivation, and the cytopathic effects in an HIV-1-latent T cell model.</p><p>In addition, we identified that the combination of JQKD82 and AZD5582, a non-canonical NF-κB activator, generates a synergistic impact on inducing HIV-1 lytic reactivation and cell death in the T cell. The latency-reversing potency of the JQKD82 and AZD5582 pair was also confirmed in peripheral blood mononuclear cells (PBMCs) isolated from HIV-1 aviremic patients and in an HIV-1 latent monocyte. In latently infected microglia (HC69) of the brain, either deletion or inhibition of KDM5A/B results in a reversal of the HIV-1 latency. Overall, we concluded that KDM5A/B function as a host repressor of the HIV-1 lytic reactivation and thus promote the latency and the survival of HIV-1 infected reservoirs.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"228 ","pages":"Article 105947"},"PeriodicalIF":4.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166354224001566/pdfft?md5=83784c23d99dd0927a8c5fcd5d0b0514&pid=1-s2.0-S0166354224001566-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454822","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}

{"title":"Targeting sgRNA N secondary structure as a way of inhibiting SARS-CoV-2 replication","authors":"Agnieszka Baliga-Gil ,&nbsp;Marta Soszynska-Jozwiak ,&nbsp;Agnieszka Ruszkowska ,&nbsp;Izabela Szczesniak ,&nbsp;Ryszard Kierzek ,&nbsp;Maria Ciechanowska ,&nbsp;Magdalena Trybus ,&nbsp;Paulina Jackowiak ,&nbsp;Jake M. Peterson ,&nbsp;Walter N. Moss ,&nbsp;Elzbieta Kierzek","doi":"10.1016/j.antiviral.2024.105946","DOIUrl":"10.1016/j.antiviral.2024.105946","url":null,"abstract":"<div><p>SARS-CoV-2 is a betacoronavirus that causes COVID-19, a global pandemic that has resulted in many infections, deaths, and socio-economic challenges. The virus has a large positive-sense, single-stranded RNA genome of ∼30 kb, which produces subgenomic RNAs (sgRNAs) through discontinuous transcription. The most abundant sgRNA is sgRNA N, which encodes the nucleocapsid (N) protein. In this study, we probed the secondary structure of sgRNA N and a shorter model without a 3ʹ UTR in vitro, using the SHAPE (selective 2ʹ-hydroxyl acylation analyzed by a primer extension) method and chemical mapping with dimethyl sulfate and 1-cyclohexyl-(2-morpholinoethyl) carbodiimide metho-p-toluene sulfonate. We revealed the secondary structure of sgRNA N and its shorter variant for the first time and compared them with the genomic RNA N structure. Based on the structural information, we designed gapmers, siRNAs and antisense oligonucleotides (ASOs) to target the N protein coding region of sgRNA N. We also generated eukaryotic expression vectors containing the complete sequence of sgRNA N and used them to screen for new SARS-CoV-2 gene N expression inhibitors. Our study provides novel insights into the structure and function of sgRNA N and potential therapeutic tools against SARS-CoV-2.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"228 ","pages":"Article 105946"},"PeriodicalIF":4.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166354224001554/pdfft?md5=6b555b273785567baeb38fd99f69fab2&pid=1-s2.0-S0166354224001554-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454895","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}

{"title":"Characterization and noncovalent inhibition of the K63-deubiquitinase activity of SARS-cov-2 PLpro","authors":"Xin Liu ,&nbsp;Miao Zheng ,&nbsp;Hongqing Zhang ,&nbsp;Bo Feng ,&nbsp;Jiaqi Li ,&nbsp;Yanan Zhang ,&nbsp;Ji Zhang ,&nbsp;Na Zhao ,&nbsp;Chaoqiang Li ,&nbsp;Ning Song ,&nbsp;Bin Song ,&nbsp;Dongyuan Yang ,&nbsp;Jin Chen ,&nbsp;Ao Qi ,&nbsp;Linxiang Zhao ,&nbsp;Cheng Luo ,&nbsp;Yi Zang ,&nbsp;Hong Liu ,&nbsp;Jia Li ,&nbsp;Bo Zhang ,&nbsp;Jie Zheng","doi":"10.1016/j.antiviral.2024.105944","DOIUrl":"10.1016/j.antiviral.2024.105944","url":null,"abstract":"<div><p>SARS-CoV-2 papain-like protease (PLpro) could facilitate viral replication and host immune evasion by respectively hydrolyzing viral polyprotein and host ubiquitin conjugates, thereby rendering itself as an important antiviral target. Yet few noncovalent PLpro inhibitors of SARS-CoV-2 have been reported with improved directed towards pathogenic deubiquitinating activities inhibition. Herein, we report that coronavirus PLpro proteases have distinctive substrate bias and are conserved to deubiquitylate K63-linked polyubiquitination, thereby attenuating host type I interferon response. We identify a noncovalent compound specifically optimized towards halting the K63-deubiquitinase activity of SARS-CoV-2 PLpro, but not other coronavirus (CoV) counterparts or host deubiquitinase. Contrasting with GRL-0617, a SARS-CoV-1 PLpro inhibitor, SIMM-036 is 50-fold and 7-fold (half maximal inhibitory concentration (IC₅₀)) more potent to inhibit viral replication during SARS-CoV-2 infection and restore the host interferon-β (IFN-β) response in human angiotensin-converting enzyme 2 (hACE2)-HeLa cells, respectively. Structure-activity relationship (SAR) analysis further reveals the importance of BL2 groove of PLpro, which could determine the selectivity of K63-deubiquitinase activity of the enzyme.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"228 ","pages":"Article 105944"},"PeriodicalIF":4.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445366","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}

{"title":"HEX17(Neumifil): An intranasal respiratory biotherapeutic with broad-acting antiviral activity","authors":"Jane A. Potter ,&nbsp;Angus Aitken ,&nbsp;Lei Yang ,&nbsp;Jennifer Hill ,&nbsp;Antoni Tortajada ,&nbsp;Julia L. Hurwitz ,&nbsp;Bart G. Jones ,&nbsp;Nadiawati Alias ,&nbsp;Mingkui Zhou ,&nbsp;Helen Connaris","doi":"10.1016/j.antiviral.2024.105945","DOIUrl":"10.1016/j.antiviral.2024.105945","url":null,"abstract":"<div><p>Broad-acting antiviral strategies to prevent respiratory tract infections are urgently required. Emerging or re-emerging viral diseases caused by new or genetic variants of viruses such as influenza viruses (IFVs), respiratory syncytial viruses (RSVs), human rhinoviruses (HRVs), parainfluenza viruses (PIVs) or coronaviruses (CoVs), pose a severe threat to human health, particularly in the very young or old, or in those with pre-existing respiratory conditions such as asthma or chronic obstructive pulmonary disease (COPD). Although vaccines remain a key component in controlling and preventing viral infections, they are unable to provide broad-spectrum protection against recurring seasonal infections or newly emerging threats. HEX17 (aka Neumifil), is a first-in-class protein-based antiviral prophylactic for respiratory viral infections. HEX17 consists of a hexavalent carbohydrate-binding module (CBM) with high affinity to sialic acids, which are typically present on terminating branches of glycans on viral cellular receptors. This allows HEX17 to block virus engagement of host receptors and inhibit infection of a wide range of viral pathogens and their variants with reduced risk of antiviral resistance. As described herein, HEX17 has demonstrated broad-spectrum efficacy against respiratory viral pathogens including IFV, RSV, CoV and HRV in multiple <em>in vivo</em> and <em>in vitro</em> studies. In addition, HEX17 can be easily administered via an intranasal spray and is currently undergoing clinical trials.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"228 ","pages":"Article 105945"},"PeriodicalIF":4.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166354224001542/pdfft?md5=6d148cabe5e92b6b9cae336352881b12&pid=1-s2.0-S0166354224001542-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445367","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}

{"title":"Dengue Virus dependence on glucokinase activity and glycolysis Confers Sensitivity to NAD(H) biosynthesis inhibitors","authors":"Eva Ogire ,&nbsp;Laure Perrin-Cocon ,&nbsp;Marianne Figl ,&nbsp;Cindy Kundlacz ,&nbsp;Clémence Jacquemin ,&nbsp;Sophie Hubert ,&nbsp;Anne Aublin-Gex ,&nbsp;Johan Toesca ,&nbsp;Christophe Ramière ,&nbsp;Pierre-Olivier Vidalain ,&nbsp;Cyrille Mathieu ,&nbsp;Vincent Lotteau ,&nbsp;Olivier Diaz","doi":"10.1016/j.antiviral.2024.105939","DOIUrl":"10.1016/j.antiviral.2024.105939","url":null,"abstract":"<div><p>Viruses have developed sophisticated strategies to control metabolic activity of infected cells in order to supply replication machinery with energy and metabolites. Dengue virus (DENV), a mosquito-borne flavivirus responsible for dengue fever, is no exception. Previous reports have documented DENV interactions with metabolic pathways and shown in particular that glycolysis is increased in DENV-infected cells. However, underlying molecular mechanisms are still poorly characterized and dependence of DENV on this pathway has not been investigated in details yet. Here, we identified an interaction between the non-structural protein 3 (NS3) of DENV and glucokinase regulator protein (GCKR), a host protein that inhibits the liver-specific hexokinase GCK. NS3 expression was found to increase glucose consumption and lactate secretion in hepatic cell line expressing GCK. Interestingly, we observed that GCKR interaction with GCK decreases DENV replication, indicating the dependence of DENV to GCK activity and supporting the role of NS3 as an inhibitor of GCKR function. Accordingly, in the same cells, DENV replication both induces and depends on glycolysis. By targeting NAD(H) biosynthesis with the antimetabolite 6-Amino-Nicotinamide (6-AN), we decreased cellular glycolytic activity and inhibited DENV replication in hepatic cells. Infection of primary organotypic liver cultures (OLiC) from hamsters was also inhibited by 6-AN. Altogether, our results show that DENV has evolved strategies to control glycolysis in the liver, which could account for hepatic dysfunctions associated to infection. Besides, our findings suggest that lowering intracellular availability of NAD(H) could be a valuable therapeutic strategy to control glycolysis and inhibit DENV replication in the liver.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"228 ","pages":"Article 105939"},"PeriodicalIF":4.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166354224001487/pdfft?md5=390b2e6286ac84363ad809e5d790fae0&pid=1-s2.0-S0166354224001487-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442072","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}

{"title":"Flexible nano-liposomes-encapsulated recombinant UL8-siRNA (r/si-UL8) based on bioengineering strategy inhibits herpes simplex virus-1 infection","authors":"Jiawei Pei ,&nbsp;Ye Tian ,&nbsp;Yamei Dang ,&nbsp;Wei Ye ,&nbsp;Xiaoqian Liu ,&nbsp;Ningbo Zhao ,&nbsp;Jiangfan Han ,&nbsp;Yongheng Yang ,&nbsp;Ziqing Zhou ,&nbsp;Xudong Zhu ,&nbsp;Hao Zhang ,&nbsp;Arshad Ali ,&nbsp;Yu Li ,&nbsp;Fanglin Zhang ,&nbsp;Yingfeng Lei ,&nbsp;Airong Qian","doi":"10.1016/j.antiviral.2024.105936","DOIUrl":"10.1016/j.antiviral.2024.105936","url":null,"abstract":"<div><p>Herpes simplex virus-1 (HSV-1) infection can cause various diseases and the current therapeutics have limited efficacy. Small interfering RNA (siRNA) therapeutics are a promising approach against infectious diseases by targeting the viral mRNAs directly. Recently, we employed a novel tRNA scaffold to produce recombinant siRNA agents with few natural posttranscriptional modifications. In this study, we aimed to develop a specific prodrug against HSV-1 infection based on siRNA therapeutics by bioengineering technology. We screened and found that UL8 of the HSV-1 genome was an ideal antiviral target based on RNAi. Next, we used a novel bio-engineering approach to manufacture recombinant UL8-siRNA (r/si-UL8) in Escherichia coli with high purity and activity. The r/si-UL8 was selectively processed to mature si-UL8 and significantly reduced the number of infectious virions in human cells. r/si-UL8 delivered by flexible nano-liposomes significantly decreased the viral load in the skin and improved the survival rate in the preventive mouse zosteriform model. Furthermore, r/si-UL8 also effectively inhibited HSV-1 infection in a 3D human epidermal skin model. Taken together, our results highlight that the novel siRNA bioengineering technology is a unique addition to the conventional approach for siRNA therapeutics and r/si-UL8 may be a promising prodrug for curing HSV-1 infection.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"228 ","pages":"Article 105936"},"PeriodicalIF":4.5,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440008","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}

{"title":"Virus infection and sphingolipid metabolism","authors":"Jun Dai ,&nbsp;Yiyi Feng ,&nbsp;Ying Liao ,&nbsp;Lei Tan ,&nbsp;Yingjie Sun ,&nbsp;Cuiping Song ,&nbsp;Xusheng Qiu ,&nbsp;Chan Ding","doi":"10.1016/j.antiviral.2024.105942","DOIUrl":"10.1016/j.antiviral.2024.105942","url":null,"abstract":"<div><p>Cellular sphingolipids have vital roles in human virus replication and spread as they are exploited by viruses for cell entry, membrane fusion, genome replication, assembly, budding, and propagation. Intracellular sphingolipid biosynthesis triggers conformational changes in viral receptors and facilitates endosomal escape. However, our current understanding of how sphingolipids precisely regulate viral replication is limited, and further research is required to comprehensively understand the relationships between viral replication and endogenous sphingolipid species. Emerging evidence now suggests that targeting and manipulating sphingolipid metabolism enzymes in host cells is a promising strategy to effectively combat viral infections. Additionally, serum sphingolipid species and concentrations could function as potential serum biomarkers to help monitor viral infection status in different patients. In this work, we comprehensively review the literature to clarify how viruses exploit host sphingolipid metabolism to accommodate viral replication and disrupt host innate immune responses. We also provide valuable insights on the development and use of antiviral drugs in this area.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"228 ","pages":"Article 105942"},"PeriodicalIF":4.5,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440009","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}

{"title":"Novel strategy for Poxviridae prevention: Thermostable combined subunit vaccine patch with intense immune response","authors":"Yuan Wen ,&nbsp;Shuyue Deng ,&nbsp;Tianmin Wang ,&nbsp;Mengtian Gao ,&nbsp;Wenlong Nan ,&nbsp;Fang Tang ,&nbsp;Qinghong Xue ,&nbsp;Yanmin Ju ,&nbsp;Jianjun Dai ,&nbsp;Yurong Wei ,&nbsp;Feng Xue","doi":"10.1016/j.antiviral.2024.105943","DOIUrl":"10.1016/j.antiviral.2024.105943","url":null,"abstract":"<div><p>Poxviruses gained international attention due to the sharp rise in monkeypox cases in recent years, highlighting the urgent need for the development of a secure and reliable vaccine. This study involved the development of an innovative combined subunit vaccine (CSV) targeting poxviruses, with lumpy skin disease virus (LSDV) serving as the model virus. To this end, the potential sites for poxvirus vaccines were fully evaluated to develop and purify four recombinant proteins. These proteins were then successfully delivered to the dermis in a mouse model by utilizing dissolvable microneedle patches (DMPs). This approach simplified the vaccination procedure and significantly mitigated the associated risk. CSV-loaded DMPs contained four recombinant proteins and a novel adjuvant, CpG, which allowed DMPs to elicit the same intensity of humoral and cellular immunity as subcutaneous injection. Following immunization with SC and DMP, the mice exhibited notable levels of neutralizing antibodies, albeit at a low concentration. It is noteworthy that the CSV loaded into DMPs remained stable for at least 4 months at room temperature, effectively addressing the storage and transportation challenges. Based on the study findings, CSV-loaded DMPs are expected to be utilized worldwide as an innovative technique for poxvirus inoculation, especially in underdeveloped regions. This novel strategy is crucial for the development of future poxvirus vaccines.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"228 ","pages":"Article 105943"},"PeriodicalIF":4.5,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442073","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}

{"title":"Influence of adjuvant type and route of administration on the immunogenicity of Leishmania-derived tick-borne encephalitis virus-like particles – A recombinant vaccine candidate","authors":"Marta Zimna ,&nbsp;Gabriela Brzuska ,&nbsp;Jiří Salát ,&nbsp;Daniel Růžek ,&nbsp;Ewelina Krol","doi":"10.1016/j.antiviral.2024.105941","DOIUrl":"10.1016/j.antiviral.2024.105941","url":null,"abstract":"<div><p>Tick-borne encephalitis virus (TBEV) is a tick-borne flavivirus that induces severe central nervous system disorders. It has recently raised concerns due to an expanding geographical range and increasing infection rates. Existing vaccines, though effective, face low coverage rates in numerous TBEV endemic regions. Our previous work demonstrated the immunogenicity and full protection afforded by a TBEV vaccine based on virus-like particles (VLPs) produced in <em>Leishmania tarentolae</em> cells in immunization studies in a mouse model. In the present study, we explored the impact of adjuvants (AddaS03™, Alhydrogel®+MPLA) and administration routes (subcutaneous, intramuscular) on the immune response. Adjuvanted groups exhibited significantly enhanced antibody responses, higher avidity, and more balanced Th1/Th2 response. IFN-γ responses depended on the adjuvant type, while antibody levels were influenced by both adjuvant and administration routes. The combination of <em>Leishmania</em>-derived TBEV VLPs with Alhydrogel® and MPLA via intramuscular administration emerged as a highly promising prophylactic vaccine candidate, eliciting a robust, balanced immune response with substantial neutralization potential.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"228 ","pages":"Article 105941"},"PeriodicalIF":4.5,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166354224001505/pdfft?md5=2e660cd5571a7ac73329f5615ef0d145&pid=1-s2.0-S0166354224001505-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431199","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}

{"title":"RBD design increases the functional antibody titers elicited by SARS-CoV-2 spike vaccination","authors":"Thayne H. Dickey ,&nbsp;Nichole D. Salinas ,&nbsp;Palak Patel ,&nbsp;Sachy Orr-Gonzalez ,&nbsp;Tarik Ouahes ,&nbsp;Holly McAleese ,&nbsp;Brandi L. Richardson ,&nbsp;Myesha Singleton ,&nbsp;Michael Murphy ,&nbsp;Brett Eaton ,&nbsp;Jennifer L. Kwan ,&nbsp;Michael R. Holbrook ,&nbsp;Lynn E. Lambert ,&nbsp;Niraj H. Tolia","doi":"10.1016/j.antiviral.2024.105937","DOIUrl":"10.1016/j.antiviral.2024.105937","url":null,"abstract":"<div><p>Most COVID-19 vaccines contain the SARS-CoV-2 spike protein as an antigen, but they lose efficacy as neutralizing antibody titers wane and escape variants emerge. Modifying the spike antigen to increase neutralizing antibody titers would help counteract this decrease in titer. We previously used a structure-based computational design method to identify nine amino acid changes in the receptor-binding domain (RBD) of spike that stabilize the RBD and increase the neutralizing antibody titers elicited by vaccination. Here, we introduce those enhancing amino acid changes into a full-length spike (FL-S-2P) ectodomain representative of most approved vaccine antigens. These amino acid changes can be incorporated into the FL-S-2P protein without negatively effecting expression or stability. Furthermore, the amino acid changes improved functional antibody titers in both mice and monkeys following vaccination. These amino acid changes could increase the duration of protection conferred by most COVID-19 vaccines.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"228 ","pages":"Article 105937"},"PeriodicalIF":4.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431223","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}