ANTIVIRAL RESEARCH 发表关于控制人类和动物病毒感染的研究报告、简短通讯、评论文章和评论。其范围包括：抗病毒药物、抗体和宿主反应调节剂，包括它们的合成、体外和体内测试以及作用机制；针对人类病毒感染的新的或改进的疫苗；药物和疫苗安全性评估；耐药病毒或疫苗耐药病毒的进化和有效对策的制定；新药靶点的识别和验证；病毒性疾病的实验动物模型；病毒性疾病的发病机制和病毒逃避宿主免疫反应的机制。

The journal "Antiviral Research" publishes research reports, short communications, review articles, and commentaries on the control of human and animal viral infections. Its scope includes: antiviral drugs, antibodies, and host response modulators, including their synthesis, in vitro and in vivo testing, and mechanisms of action; new or improved vaccines for human viral infections; safety assessments of drugs and vaccines; the evolution of drug-resistant viruses or vaccine-resistant viruses and the development of effective countermeasures; identification and validation of new drug targets; experimental animal models of viral diseases; and mechanisms of viral diseases and how viruses evade host immune responses.

《Antiviral Research》期刊发表关于控制人类和动物病毒感染的研究报告、简短通讯、评论文章及综述。其研究范围包括：抗病毒药物、抗体及宿主反应调节剂的合成、体外和体内测试及作用机制；针对人类病毒感染的新型或改进疫苗；药物和疫苗的安全性评估；耐药病毒或疫苗耐药病毒的进化及有效对策的制定；新药靶点的识别与验证；病毒性疾病的实验动物模型；病毒性疾病的发病机制及病毒逃避宿主免疫反应的机制。

Antiviral Research

Coxsackievirus A10 (CVA10) has emerged worldwide as one of the main pathogens of hand, foot, and mouth disease (HFMD) in recent years. However, there is currently no commercial vaccine available to prevent CVA10 infection. Here we report the development of a recombinant virus-like particle (VLP) based candidate vaccine for CVA10. Co-expression of the capsid protein precursor P1 and the protease 3CD of CVA10 in Pichia pastoris resulted in cleavage of P1 into three capsid subunit proteins VP0, VP1, and VP3. These three subunit proteins co-assembled into CVA10 VLPs, which were visualized as spherical particles with a diameter of ∼30 nm under electron microscope. Immunization studies showed that CVA10 VLP could efficiently induce antigen-specific serum antibodies in mice. The anti-VLP sera were able to potently neutralize homologous and heterologous CVA10 strains. Importantly, passively transferred anti-VLP sera fully protected recipient neonatal mice from lethal CVA10 infection. In addition, neonatal mice born to the VLP-immunized dams were also completely protected from CVA10 lethal challenge. Collectively, these data show that CVA10 VLP represents a promising CVA10 vaccine candidate.

Yu Zhou

Chao Zhang

Qingwei Liu

Sitang Gong

Lanlan Geng

Zhong Huang

Antiviral research

Antiviral Res

A virus-like particle vaccine protects mice against coxsackievirus A10 lethal infection.

The discovery of novel antivirals to treat hepatitis B virus (HBV) infection is urgently needed, as the currently available drugs mainly target viral proteins at replication step, whereas host factors also play significant roles in HBV infection. Although numerous studies have reported candidate drugs for HBV treatment, there remains a need to find a new drug that may target other steps of the HBV life cycle. In this study, by drug screening of a 533 G-protein-coupled receptors (GPCRs)-associated compound library, we identified ponesimod, a selective agonist of sphingosine-1-phosphate receptor 1 (S1P1), as a drug candidate for the suppression of HBV infection. However, the anti-HBV effect of ponesimod is independent of S1P1 and other sphingosine-1-phosphate receptors (S1PRs). Treatment with ponesimod at an early step of infection but not at a post-entry step significantly reduced the HBV relaxed circular DNA (rcDNA) level in a dose-dependent manner. Ponesimod treatment did not inhibit attachment, binding, or internalization of HBV particles via endocytosis through an interaction with sodium taurocholate cotransporting polypeptide (NTCP) or epidermal growth factor receptor (EGFR). Importantly, during the transportation of HBV particles to the nucleus, co-localization of HBV with early endosomes but not with late endosomes and lysosomes was induced by the treatment with ponesimod, suggesting that ponesimod interferes with the conversion of early endosomes to late endosomes without significant damage to cellular growth. Conclusion: Ponesimod is a promising anti-HBV drug targeting the endosome maturation of HBV. This finding can be applied to the development of novel antivirals that target the trafficking pathway of HBV particles.

Yuzy Fauzyah

Chikako Ono

Shiho Torii

Itsuki Anzai

Rigel Suzuki

Takuma Izumi

Yuhei Morioka

Yusuke Maeda

Toru Okamoto

Takasuke Fukuhara

Yoshiharu Matsuura

Ponesimod suppresses hepatitis B virus infection by inhibiting endosome maturation

Ponesimod通过抑制内体成熟抑制乙型肝炎病毒感染

SARS-CoV-2 is the causative agent of the immune response-driven disease COVID-19 for which new antiviral and anti-inflammatory treatments are urgently needed to reduce recovery time, risk of death and long COVID development. Here, we demonstrate that the immunoregulatory kinase p38 MAPK is activated during viral entry, mediated by the viral spike protein, and drives the harmful virus-induced inflammatory responses. Using primary human lung explants and lung epithelial organoids, we demonstrate that targeting p38 signal transduction with the selective and clinically pre-evaluated inhibitors PH-797804 and VX-702 markedly reduced the expression of the pro-inflammatory cytokines IL6, CXCL8, CXCL10 and TNF-α during infection, while viral replication and the interferon-mediated antiviral response of the lung epithelial barrier were largely maintained. Furthermore, our results reveal a high level of drug synergism of both p38 inhibitors in co-treatments with the nucleoside analogs Remdesivir and Molnupiravir to suppress viral replication of the SARS-CoV-2 variants of concern, revealing an exciting and novel mode of synergistic action of p38 inhibition. These results open new avenues for the improvement of the current treatment strategies for COVID-19.

Aileen Faist

Sebastian Schloer

Angeles Mecate-Zambrano

Josua Janowski

André Schreiber

Yvonne Boergeling

Beate C.G. Conrad

Sriram Kumar

Leonie Toebben

Klaus Schughart

Morris Baumgardt

Mirjana Kessler

Katja Hoenzke

Andreas Hocke

Marcel Trautmann

Wolfgang Hartmann

Hiroki Kato

Ursula Rescher

Anmari Christersson

Joachim Kuehn

Alexander Mellmann

Thorsten Wolff

Philip Kuempers

Alexandros Rovas

Rainer Wiewrodt

Karsten Wiebe

Peter Barth

Stephan Ludwig

Linda Brunotte

Inhibition of p38 signaling curtails the SARS-CoV-2 induced inflammatory response but retains the IFN-dependent antiviral defense of the lung epithelial barrier

抑制p38信号可减少SARS-CoV-2引发的炎症反应，同时保留肺上皮屏障的IFN依赖性抗病毒防御

Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that causes severe morbidity and mortality in piglets, resulting in substantial economic losses to the swine industry. While vaccination is currently the most effective preventive measure, existing vaccines fail to provide complete and reliable protection against PEDV infection. Consequently, there is a need to explore alternative or complementary strategies to address this issue. In this study, we utilized single B cell antibody technology to obtain a potent neutralizing antibody, C62, which specifically targets the receptor binding domain S1B of the PEDV-S1 protein. C62 exhibited potent neutralizing activity against PEDV and inhibited viral attachment to the cell surface in vitro. Furthermore, the effectiveness of C62 in mitigating PEDV infection was demonstrated in vivo, as evidenced by the delayed onset of diarrhea and reduced mortality rates observed in piglets following oral administration of C62. Our study provides an alternative approach for controlling PEDV infection. Meanwhile, C62 holds promise as a therapeutic biological agent to complement existing vaccines. More importantly, our study forms a solid foundation for the development of whole-porcine neutralizing antibodies against other swine coronaviruses, thus contributing to the overall improvement of swine health.

Sheng Wang

Zhichen Wang

Ying Li

Shaoyu Tu

Jiahui Zou

Yanqing Cheng

Huawei Zhang

Sizhu Suolang

Hongbo Zhou

Generation of whole-porcine neutralizing antibodies of an alphacoronavirus by single B cell antibody technology.

通过单B细胞抗体技术生成全猪源中和α冠状病毒抗体。

Cervical cancer, often driven by high-risk human papillomavirus (HPV) infections such as HPV16 or HPV18, remains a leading cause of cancer-related deaths. HPV16, found in about 90% of cervical cancer patients, harbors key oncogenic related genes (E6, E7, E2, E5) and an upstream regulatory region (URR) that contribute to cancer progression. This study introduces a novel approach using a recombinant oncolytic herpes simplex virus type 1 (HSV-1) named SONC103, armed with a CRISPR/Cas9 gene editing system. The aim was to target and disrupt integrated HPV16 genes in cervical cancer cells. Results demonstrated SONC103's capability to specifically and effectively knock down HPV16 oncogenes, thereby reducing cell proliferation and promoting apoptosis. Analyses further revealed loss of HPV16 DNA probes in infected cells' chromosomes, significant regulation of cellular processes related to tumor apoptosis, and downregulation of E6/E7 oncoproteins while increasing tumor suppressor proteins P53 and pRB. Notably, SONC103 exhibited substantial inhibition of tumor growth in a murine xenograft cervical cancer model. This study showcases the potential of the recombinant oncolytic HSV-1 virus (SONC103) in combating HPV16-positive cervical cancer by targeting oncogenes and facilitating oncolysis.

Zongfeng Hu

Wenqi Liu

Jiajia Liu

Hua Zhou

Chunyang Sun

None ChaoTian

Xiaona Guo

Chengyang Zhu

Mingxia Shao

Shengrun Wang

Lijun Wei

Min Liu

Shuzhen Li

Jinyu Wang

Haitian Xu

Wei Zhu

Xiaopeng Li

Jingfeng Li

The anti-tumor efficacy of a recombinant oncolytic herpes simplex virus mediated CRISPR/Cas9 delivery targeting in HPV16-positive cervical cancer

靶向HPV16阳性宫颈癌的重组溶瘤单纯疱疹病毒介导的CRISPR/Cas9递送的抗肿瘤疗效

Nopporn Chutiwitoonchai

Radeekorn Akkarawongsapat

Suphat Chantawarin

Chutima Jiarpinitnun

Benjamas Liwnaree

Samaporn Teeravechyan

Sunhapas Soodvilai

Antiviral effect of pinostrobin, a bioactive constituent of Boesenbergia rotunda, against porcine epidemic diarrhea virus

抗猪流行性腹泻病毒的活性成分圆瓣姜花中的匹诺斯卓宾的抗病毒作用

While the COVID-19 crisis is still ongoing, a new public health threat has emerged with recent outbreaks of monkeypox (mpox) infections in Africa. Mass vaccination is not currently recommended by the World Health Organization (WHO), and antiviral treatments are yet to be specifically approved for mpox, although existing FDA-approved drugs (Tecovirimat, Brincidofovir, and Cidofovir) may be used in severe cases or for immunocompromised patients. A first-line of defense is thus drug repurposing, which was heavily attempted against SARS-CoV-2 - albeit with limited success. This review focuses on nucleoside analogues as promising antiviral candidates for targeting of the viral DNA-dependent DNA polymerase. In contrast to broad-spectrum screening approaches employed for SARS-CoV-2, we emphasize the importance of understanding the structural specificity of viral polymerases for rational selection of potential candidates. By comparing DNA-dependent DNA polymerases with other viral polymerases, we highlight the unique features that influence the efficacy and selectivity of nucleoside analogues. These structural insights provide a framework for the preselection, repurposing, optimization, and design of nucleoside analogues, aiming to accelerate the development of targeted antiviral therapies for mpox and other viral infections.

Ashleigh Shannon

Bruno Canard

Nucleotide analogues and Mpox : Repurposing the repurposable

核苷酸类似物与猴痘：重新利用可再利用的药物

Serum HBV-RNA (seRNA) was proposed to be a circulating marker of cccDNA transcriptional activity in hepatocytes. The combination of tenofovir-disoproxil-fumarate (TDF) and pegylated-interferon-alpha-2a (pegIFN) with nucleic-acid polymer (NAP) treatment was associated with a relatively high rate of functional cure (FC) 48 weeks after discontinuation of all therapy. We aim to characterize seRNA kinetics under TDF and pegIFN±NAP combination therapies. Forty participants with chronic HBV in the REP401 phase-II clinical trial received 48 weeks of triple combination therapy with NAPs, pegIFN, and TDF. For 20 participants, triple combination therapy (TDF+pegIFN+NAPs) followed 24 weeks of TDF. For 20 other participants, triple combination therapy followed 24 weeks of TDF monotherapy and 24 weeks of dual therapy (TDF+pegIFN). The Abbott RUO assay for HBV RNA (LLoQ=1.65 logU/mL) was performed every 4 weeks. Previously unrecognized seRNA kinetic patterns were identified with dual/triple therapy including (i) no change (ii) an seRNA increase followed by a new elevated plateau (only under dual therapy) and (iii) a transient increase followed by a spontaneous decline. All participants establishing a new elevated seRNA plateau level experienced a subsequent monophasic decline following the introduction of NAPs. Failure to reach seRNA LLoQ by 16 weeks of triple therapy had a negative predictive value of 100% for FC. The median seRNA half-life for participants in the virological-rebound group was significantly (p=0.01) longer than in the partial and FC groups (5.7 vs 2.7 weeks, respectively). Achieving partial/functional cure is associated with a shorter seRNA half-life, which could reflect faster inactivation of cccDNA transcriptional activity.

Leeor Hershkovich

Scott J Cotler

Louis Shekhtman

Michel Bazinet

Mark Anderson

Mary Kuhns

Gavin Cloherty

Andrew Vaillant

Harel Dahari

HBV serum RNA kinetics during nucleic acid polymers based therapy predict functional cure

基于核酸聚合物治疗期间HBV血清RNA动力学预测功能性治愈

Nicola Frericks

Mara Klöhn

Frauke Lange

Lilli Pottkämper

Arnaud Carpentier

Eike Steinmann

Host-Targeting Antivirals for Chronic Viral Infections of the Liver

针对肝脏慢性病毒感染的宿主导向抗病毒药物

Chiwei Peng

Fang Wu

Yanhong Ma

Guolong Liu

Yin Huang

Rongbiao Tong

Wei Xu

Ginkgolic acid Inhibits Ebola Virus Transcription and Replication by Disrupting the Interaction Between Nucleoprotein and VP30 Protein

银杏酸通过破坏核蛋白与VP30蛋白的相互作用抑制埃博拉病毒的转录和复制

Abbreviation	Antiviral. Res.
Journal Impact	4.63
Quartiles(Global)	VIROLOGY(Q1)

ISSN	0166-3542, 1872-9096
h-index	151

Publication Information	Publisher: Elsevier B.V.，Publishing cycle: Monthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1981，Proportion of original research papers: 100.00%，Self Citation Rate:4.40%， Gold OA Rate: 44.99%
Average review cycle	网友分享经验：平均3.0个月来源Elsevier官网：平均9.6周
Average recruitment ratio	网友分享经验：约25%

Antiviral Research

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