Yucai Liang, Weiling Xiao, Yuan Peng, Shengshuo Zhang, Jinhua Dong, Jun Zhao, Yuhui Wang, Mengtao Zhang, Zhijun Liu, Bowen Yu
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...
May 21, 2024: Antiviral Research
Na Jiang, Yating He, Jing Wu, Qiao You, Rui Zhang, Min Cheng, Bingxin Liu, Yurong Cai, Ruining Lyu, Zhiwei Wu
The severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus, recently being officially renamed as Dabie bandavirus, and a causative agent for an emerging infectious disease associated with high fatality. Effective therapeutics and vaccines are lacking and disease pathogenesis is yet to be fully elucidated. In our effort to identify new SFTSV inhibitory molecules, 6-Thioguanine (6-TG) was found to potently inhibit SFTSV infection. 6-TG has been widely used as therapeutic agent since the approval of the Food and Drug Administration in the 1960s...
May 20, 2024: Antiviral Research
Bing Liang Alvin Chew, Qi Pan, Hongli Hu, Dahai Luo
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...
May 20, 2024: Antiviral Research
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 Adhikari, Anusarka Bhaumik, Aaron Patrick, Amy Fung, Priscila Sutto-Ortiz, Etienne Decroly, Stephen W Mason, David Lançois, Jerome Deval, Zhinan Jin, Jean-François Eléouët, Rachel Fearns, Anil Koul, Dirk Roymans, Peter Rigaux, Florence Herschke
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 suggested JNJ-7184 binds RSV-L in the connector domain. JNJ-7184 prevented RSV replication and transcription by inhibiting initiation or early elongation...
May 19, 2024: Antiviral Research
Francisco J Mancebo, Marcos Nuévalos, Jaanam Lalchandani, Antonio J Martín Galiano, Mario Fernández-Ruiz, José María Aguado, Estéfani García-Ríos, Pilar Pérez-Romero
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. 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...
May 15, 2024: Antiviral Research
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
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...
May 11, 2024: Antiviral Research
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
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 Phoma herbarum DBE-M1, to stimulate lytic replication of EBV in B95-8 cells...
May 10, 2024: Antiviral Research
Ian Santisteban Celis, Nobuyuki Matoba
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...
May 9, 2024: Antiviral Research
Sheila M Keating, Brett W Higgins
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...
May 9, 2024: Antiviral Research
Kabita Pandey, Arpan Acharya, Dhananjaya Pal, Prashant Jain, Kamal Singh, Donald L Durden, Tatiana G Kutateladze, Aniruddha J Deshpande, Siddappa N Byrareddy
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 IC50 values at sub-micromolar concentrations without any impact on the cell proliferation of Calu-3 cells at and below its IC50 concentration...
May 8, 2024: Antiviral Research
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
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...
May 7, 2024: Antiviral Research
Hancheng Guan, Manunya Nuth, Richard W Scott, Michael H Parker, Eric D Strobel, Allen B Reitz, John L Kulp, Robert P Ricciardi
We recently developed compound FC-7269 for targeting the Molluscum contagiosum virus processivity factor (mD4) and demonstrated its ability to inhibit viral processive DNA synthesis in vitro and cellular infection of an mD4-dependent virus (Antiviral Res 211, 2023,105520). However, despite a thorough medicinal chemistry campaign we were unable to generate a potent second analog as a requisite for drug development. We overcame this impasse, by conjugating a short hydrophobic trivaline peptide to FC-7269 to produce FC-TriVal-7269 which significantly increased antiviral potency and reduced cellular toxicity...
May 3, 2024: Antiviral Research
Xian Li, Zhong-Wang Zhang, Fu-Dong Zhang, Jia-Hao Li, Jian-Liang Lv, Li-Ping Zhang, Kai-Ge Zhai, Yong-Lu Wang, Hui-Chen Guo, Xin-Sheng Liu, Li Pan
BACKGROUND & AIMS: The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. PATIENTS AND METHODS: Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL)...
May 3, 2024: Antiviral Research
Xiaochun Liu, Yanqing Wang, Lishan Sun, Guokai Xiao, Ning Hou, Jin Chen, Wei Wang, Ximing Xu, Yuchao Gu
SARS-CoV-2 continues to threaten human health, antibody therapy is one way to control the infection. Because new SARS-CoV-2 mutations are constantly emerging, there is an urgent need to develop broadly neutralizing antibodies to block the viral entry into host cells. VNAR from sharks is the smallest natural antigen binding domain, with the advantages of small size, flexible paratopes, good stability, and low manufacturing cost. Here, we used recombinant SARS-CoV-2 Spike-RBD to immunize sharks and constructed a VNAR phage display library...
April 29, 2024: Antiviral Research
Irene Arduino, Rachele Francese, Andrea Civra, Elisa Feyles, Monica Argenziano, Marco Volante, Roberta Cavalli, Ali M Mougharbel, Ulrich Kortz, Manuela Donalisio, David Lembo
Human respiratory viruses have an enormous impact on national health systems, societies, and economy due to the rapid airborne transmission and epidemic spread of such pathogens, while effective specific antiviral drugs to counteract infections are still lacking. Here, we identified two Keggin-type polyoxometalates (POMs), [TiW11 CoO40 ]8- (TiW11 Co) and [Ti2 PW10 O40 ]7- (Ti2 PW10 ), endowed with broad-spectrum activity against enveloped and non-enveloped human respiratory viruses, i.e., coronavirus (HCoV-OC43), rhinovirus (HRV-A1), respiratory syncytial virus (RSV-A2), and adenovirus (AdV-5)...
April 27, 2024: Antiviral Research
Thomas Michler, Jakob Zillinger, Philipp Hagen, Fuwang Cheng, Julia Festag, Anna Kosinska, Ulrike Protzer
Immune tolerance to the hepatitis B virus (HBV) is crucial for developing chronic hepatitis, and the HBV surface antigen (HBsAg) produced and secreted in high amounts is regarded as a key contributor. HBsAg is expressed in HBV-infected hepatocytes and those carrying an HBV integration. Whether either HBsAg secretion or the high antigen amount expressed in the liver determines its immunomodulatory properties, however, remains unclear. We, therefore, developed a novel HBV animal model that allowed us to study the role of secreted HBsAg...
April 26, 2024: Antiviral Research
Adam J Gehring, Loghman Salimzadeh
With the increasing momentum and success of monoclonal antibody therapy in conventional medical practices, there is a revived emphasis on the development of monoclonal antibodies targeting the hepatitis B surface antigen (anti-HBs) for the treatment of chronic hepatitis B (HBV) and hepatitis D (HDV). Combination therapies of anti-HBs monoclonal antibodies, and novel anti-HBV compounds and immunomodulatory drugs presenting a promising avenue to enhanced therapeutic outcomes in HBV/HDV cure regimens. In this review, we will cover the role of antibodies in the protection and clearance of HBV infection, the association of anti-HBV surface antigen antibodies (anti-HBs) in protection against HBV and how antibody effector functions, beyond neutralization, are likely necessary...
April 26, 2024: Antiviral Research
Nicole Bracci, Alan Baer, Rafaela Flor, Kaylee Petraccione, Timothy Stocker, Weidong Zhou, Tatiana Ammosova, Rhoel R Dinglasan, Sergei Nekhai, Kylene Kehn-Hall
Rift Valley fever virus (RVFV) is an arbovirus in the Phenuiviridae family identified initially by the large 'abortion storms' observed among ruminants; RVFV can also infect humans. In humans, there is a wide variation of clinical symptoms ranging from subclinical to mild febrile illness to hepatitis, retinitis, delayed-onset encephalitis, or even hemorrhagic fever. The RVFV is a tri-segmented negative-sense RNA virus consisting of S, M, and L segments. The L segment encodes the RNA-dependent RNA polymerase (RdRp), termed the L protein, which is responsible for both viral mRNA synthesis and genome replication...
April 26, 2024: Antiviral Research
Rohan Ameratunga, Anthony Jordan, Klaus Lehnert, Euphemia Leung, Emily R Mears, Russell Snell, Richard Steele, See-Tarn Woon
COVID-19 has caused calamitous health, economic and societal consequences. Although several COVID-19 vaccines have received full authorization for use, global deployment has faced political, financial and logistical challenges. The efficacy of first-generation COVID-19 vaccines is waning and breakthrough infections are allowing ongoing transmission and evolution of SARS-CoV-2. Furthermore, COVID-19 vaccine efficacy relies on a functional immune system. Despite receiving three primary doses and three or more heterologous boosters, some immunocompromised patients may not be adequately protected by COVID-19 vaccines and remain vulnerable to severe disease...
April 25, 2024: Antiviral Research
Kai Liu, Liushuai Li, Yajie Liu, Xi Wang, Jia Liu, Jiang Li, Fei Deng, Runze Zhang, Yiwu Zhou, Zhihong Hu, Wu Zhong, Manli Wang, Chun Guo
Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic bunyavirus with a fatality rate of up to 40%. Currently, there are no licensed antiviral drugs for the treatment of CCHF; thus, the World Health Organization (WHO) listed the disease as a priority. A unique viral transcription initiation mechanism called "cap-snatching" is shared by influenza viruses and bunyaviruses. Thus, we tested whether baloxavir (an FDA-approved anti-influenza drug that targets the "cap-snatching" mechanism) could inhibit CCHFV infection...
April 22, 2024: Antiviral Research
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