High content screening strategies for large-scale compound libraries with a focus on high-containment viruses
Antiviral Res. 2023 Nov 24:105764. doi: 10.1016/j.antiviral.2023.105764. Online ahead of print.ABSTRACTA majority of viral diseases do not have FDA-approved drugs. The recent outbreaks caused by SARS-CoV-2, monkeypox, and Sudan ebolavirus have exposed the critical need for rapid screening and identification of antiviral compounds against emerging/re-emerging viral pathogens. A high-content screening (HCS) platform is becoming an essential part of the drug discovery process, thanks to developments in image acquisition and analysis. While HCS has several advantages, its full potential has not been realized in antiviral drug ...
Source: Antiviral Research - November 26, 2023 Category: Virology Authors: Chandru Subramani Ghanshyam Sharma Tridib Chaira Tarani Kanta Barman Source Type: research
A phenothiazine urea derivative broadly inhibits coronavirus replication via viral protease inhibition
Antiviral Res. 2023 Nov 24:105758. doi: 10.1016/j.antiviral.2023.105758. Online ahead of print.ABSTRACTCoronavirus (CoV) replication requires efficient cleavage of viral polyproteins into an array of non-structural proteins involved in viral replication, organelle formation, viral RNA synthesis, and host shutoff. Human CoVs (HCoVs) encode two viral cysteine proteases, main protease (Mpro) and papain-like protease (PLpro), that mediate polyprotein cleavage. Using a structure-guided approach, a phenothiazine urea derivative that inhibits both SARS-CoV-2 Mpro and PLpro protease activity was identified. In silico docking studi...
Source: Antiviral Research - November 26, 2023 Category: Virology Authors: Katrina Forrestall Eric S Pringle Dane Sands Brett A Duguay Brett Farewell Tekeleselassie Woldemariam Darryl Falzarano Ian Pottie Craig McCormick Sultan Darvesh Source Type: research
A novel phthalazinone derivative as a capsid assembly modulator inhibits hepatitis B virus expression
In this study, we intend to elaborate the antiviral effect and mechanism of 5832 against HBV in vitro and in vivo. Compound 5832 treatment induces the formation of genome-free empty capsid by interfering with the core protein assembly domain, which significantly decreases the extracellular and intracellular HBV DNA. In the AAV-HBV transduced mouse model, 5832 suppresses serum HBV DNA after 4-week treatment, and decreases HBsAg and HBeAg levels. 5832 treatment also reduces intrahepatic HBV RNA, DNA and HBcAg levels. During the follow-up period after treatment withdrawal, serum antigen levels demonstrated no increase. We dem...
Source: Antiviral Research - November 26, 2023 Category: Virology Authors: Li Yang Ying Gong Feifei Liu Wuhong Chen Xinran Wang Guozhang Long Heng Li Fuling Xiao MengJi Lu Youhong Hu Xiankun Tong Jianping Zuo Source Type: research
High content screening strategies for large-scale compound libraries with a focus on high-containment viruses
Antiviral Res. 2023 Nov 24:105764. doi: 10.1016/j.antiviral.2023.105764. Online ahead of print.ABSTRACTA majority of viral diseases do not have FDA-approved drugs. The recent outbreaks caused by SARS-CoV-2, monkeypox, and Sudan ebolavirus have exposed the critical need for rapid screening and identification of antiviral compounds against emerging/re-emerging viral pathogens. A high-content screening (HCS) platform is becoming an essential part of the drug discovery process, thanks to developments in image acquisition and analysis. While HCS has several advantages, its full potential has not been realized in antiviral drug ...
Source: Antiviral Research - November 26, 2023 Category: Virology Authors: Chandru Subramani Ghanshyam Sharma Tridib Chaira Tarani Kanta Barman Source Type: research
A phenothiazine urea derivative broadly inhibits coronavirus replication via viral protease inhibition
Antiviral Res. 2023 Nov 24:105758. doi: 10.1016/j.antiviral.2023.105758. Online ahead of print.ABSTRACTCoronavirus (CoV) replication requires efficient cleavage of viral polyproteins into an array of non-structural proteins involved in viral replication, organelle formation, viral RNA synthesis, and host shutoff. Human CoVs (HCoVs) encode two viral cysteine proteases, main protease (Mpro) and papain-like protease (PLpro), that mediate polyprotein cleavage. Using a structure-guided approach, a phenothiazine urea derivative that inhibits both SARS-CoV-2 Mpro and PLpro protease activity was identified. In silico docking studi...
Source: Antiviral Research - November 26, 2023 Category: Virology Authors: Katrina Forrestall Eric S Pringle Dane Sands Brett A Duguay Brett Farewell Tekeleselassie Woldemariam Darryl Falzarano Ian Pottie Craig McCormick Sultan Darvesh Source Type: research
In vitro evaluation of tropolone absorption, metabolism, and clearance
Antiviral Res. 2023 Nov 21:105762. doi: 10.1016/j.antiviral.2023.105762. Online ahead of print.ABSTRACTTropolone compounds can inhibit hepatitis B virus (HBV) replication at sub-micromolar levels and are synergistic upon co-treatment with nucleos(t)ide analog drugs. However, only a few compounds within this chemotype have been screened for their pharmacological properties. Here, we chose 36 structurally diverse tropolones from six subclasses to characterize their in vitro pharmacological parameters. All compounds were more soluble in pHs that reflect the gastrointestinal tract (pH 5 and 6.5) than plasma (pH 7.4). Those com...
Source: Antiviral Research - November 23, 2023 Category: Virology Authors: Molly E Woodson M Abdul Mottaleb Ryan P Murelli John E Tavis Source Type: research
In vitro evaluation of tropolone absorption, metabolism, and clearance
Antiviral Res. 2023 Nov 21:105762. doi: 10.1016/j.antiviral.2023.105762. Online ahead of print.ABSTRACTTropolone compounds can inhibit hepatitis B virus (HBV) replication at sub-micromolar levels and are synergistic upon co-treatment with nucleos(t)ide analog drugs. However, only a few compounds within this chemotype have been screened for their pharmacological properties. Here, we chose 36 structurally diverse tropolones from six subclasses to characterize their in vitro pharmacological parameters. All compounds were more soluble in pHs that reflect the gastrointestinal tract (pH 5 and 6.5) than plasma (pH 7.4). Those com...
Source: Antiviral Research - November 23, 2023 Category: Virology Authors: Molly E Woodson M Abdul Mottaleb Ryan P Murelli John E Tavis Source Type: research
In vitro evaluation of tropolone absorption, metabolism, and clearance
Antiviral Res. 2023 Nov 21:105762. doi: 10.1016/j.antiviral.2023.105762. Online ahead of print.ABSTRACTTropolone compounds can inhibit hepatitis B virus (HBV) replication at sub-micromolar levels and are synergistic upon co-treatment with nucleos(t)ide analog drugs. However, only a few compounds within this chemotype have been screened for their pharmacological properties. Here, we chose 36 structurally diverse tropolones from six subclasses to characterize their in vitro pharmacological parameters. All compounds were more soluble in pHs that reflect the gastrointestinal tract (pH 5 and 6.5) than plasma (pH 7.4). Those com...
Source: Antiviral Research - November 23, 2023 Category: Virology Authors: Molly E Woodson M Abdul Mottaleb Ryan P Murelli John E Tavis Source Type: research
Proteomic and phosphoproteomic analysis of responses to enterovirus A71 infection reveals novel targets for antiviral and viral replication
In this report, we used proteomic and phosphorylated proteomic methods to characterize the proteome and phosphoproteome profiles of EV-A71-infected human neuroblastoma SK-N-SH cells. More than 7744 host proteins and 10069 phosphorylation modification sites were successfully quantified. Among them, 974 proteins and 3648 phosphorylation modification sites were regulated significantly during EV-A71 infection. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis revealed that EV-A71 altered cell biological processes, including protein synthesis, RNA splicing and metabolism in SK-N-SH cells. Notably, based on the pre...
Source: Antiviral Research - November 22, 2023 Category: Virology Authors: Dandan Lin Xiaojing Dong Xia Xiao Zichun Xiang Xiaobo Lei Jianwei Wang Source Type: research
SRPKIN-1 as an inhibitor against hepatitis B virus blocking the viral particle formation and the early step of the viral infection
In this study, the SRPK inhibitors SPHINX31, SRPIN340, and SRPKIN-1 showed concentration-dependent anti-HBV activity. Detailed analysis of the effects of SRPKIN-1, which exhibited the strongest inhibitory activity, on the HBV replication process showed that it inhibits the formation of infectious particles by inhibiting pregenomic RNA packaging into capsids and nucleocapsid envelopment. Mass spectrometry analysis combined with cell-free translation system experiments revealed that hyperphosphorylation of the C-terminal domain of HBc is inhibited by SRPKIN-1. Further, SRPKIN-1 exhibited concentration-dependent inhibition of...
Source: Antiviral Research - November 22, 2023 Category: Virology Authors: Xiaofang Li Kenji Nakashima Masahiko Ito Mami Matsuda Takeshi Chida Kazumasa Sekihara Hirotaka Takahashi Takanobu Kato Tatsuya Sawasaki Tetsuro Suzuki Source Type: research
Lung transcriptomics of K18-hACE2 mice highlights mechanisms and genes involved in the MVA-S vaccine-mediated immune response and protection against SARS-CoV-2 infection
This study shows host transcriptomic mechanisms likely involved in the MVA-S vaccine-mediated immune response against SARS-CoV-2 infection, which could help in improving vaccine dose assessment and developing novel, well-optimized SARS-CoV-2 vaccine candidates against prevalent or emerging VoCs.PMID:37992765 | DOI:10.1016/j.antiviral.2023.105760 (Source: Antiviral Research)
Source: Antiviral Research - November 22, 2023 Category: Virology Authors: Alberto G ómez-Carballa Guillermo Albericio Juli án Montoto-Louzao Patricia P érez David Astorgano Irene Rivero-Calle Federico Martin ón-Torres Mariano Esteban Antonio Salas Juan Garc ía-Arriaza Source Type: research
Licochalcone A regulates viral IRES activity to inhibit enterovirus replication
Antiviral Res. 2023 Nov 18:105755. doi: 10.1016/j.antiviral.2023.105755. Online ahead of print.ABSTRACTEnterovirus D68 (EV-D68), belonging to the genus Enterovirus of the Picornavirus family, is an emerging pathogen that can cause neurological and respiratory diseases in children. However, there is little understanding of the pathogenesis of EV-D68, and no effective vaccine or drug for the prevention or treatment of the diseases caused by this virus is available. Autophagy is a cellular process that targets cytoplasmic proteins or organelles to the lysosomes for degradation. Enteroviruses strategically harness the host aut...
Source: Antiviral Research - November 20, 2023 Category: Virology Authors: Yu-Ting Chuang Yu-Li Lin Jing-Yi Lin Source Type: research
Newcastle Disease Virus (NDV)-based vaccine candidate against SARS-CoV-2 Omicron by intranasal immunization
Antiviral Res. 2023 Nov 18:105757. doi: 10.1016/j.antiviral.2023.105757. Online ahead of print.ABSTRACTDespite global vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread globally. Currently, the development of affordable vaccine against Omicron variant of concern (VOC) is necessary. Here, we assessed the safety and immunogenicity of a SARS-CoV-2 vaccine consisting of a live Newcastle disease virus vector expressing the spike (S) protein of Omicron BA.1 administrated intranasally (IN) or intramuscularly (IM) in Golden Syrian hamster model. Immunogenicity studies s...
Source: Antiviral Research - November 20, 2023 Category: Virology Authors: Qiu-Yan Zhang Hong-Qing Zhang Ya-Nan Zhang Zhe-Rui Zhang Xiao-Dan Li Meng-Chan Hao Yang Zhang Jia-Qi Li Yan-Yan Hu Xiao-Ling Chen Jing Wang Yu-Jia Shi Cheng-Lin Deng Jian-Jun Chen Han-Qing Ye Bo Zhang Source Type: research
Monoglycosylated SARS-CoV-2 receptor binding domain fused with HA < sub > stem < /sub > -scaffolded protein vaccine confers broad protective immunity against SARS-CoV-2 and influenza viruses
This study demonstrated that HSSRmg produced using a monoglycosylation process and combined with the JR300 adjuvant elicits superior cross-strain immune responses against SARS-CoV-2 and influenza viruses in mice compared with S-2P. JR300-adjuvanted HSSRmg has great potential as a coronavirus-influenza vaccine that provides dual protection against SARS-CoV-2 and influenza infections.PMID:37984568 | DOI:10.1016/j.antiviral.2023.105759 (Source: Antiviral Research)
Source: Antiviral Research - November 20, 2023 Category: Virology Authors: Chia-Ying Wu Yung-Chieh Tseng Shao-En Kao Li-Yang Wu Jen-Tzu Hou Yu-Chih Yang Pei-Wen Hsiao Juine-Ruey Chen Source Type: research
Licochalcone A regulates viral IRES activity to inhibit enterovirus replication
Antiviral Res. 2023 Nov 18:105755. doi: 10.1016/j.antiviral.2023.105755. Online ahead of print.ABSTRACTEnterovirus D68 (EV-D68), belonging to the genus Enterovirus of the Picornavirus family, is an emerging pathogen that can cause neurological and respiratory diseases in children. However, there is little understanding of the pathogenesis of EV-D68, and no effective vaccine or drug for the prevention or treatment of the diseases caused by this virus is available. Autophagy is a cellular process that targets cytoplasmic proteins or organelles to the lysosomes for degradation. Enteroviruses strategically harness the host aut...
Source: Antiviral Research - November 20, 2023 Category: Virology Authors: Yu-Ting Chuang Yu-Li Lin Jing-Yi Lin Source Type: research