Molecular mechanisms of tetrahydropyrrolo[1,2-c]pyrimidines as HBV capsid assembly inhibitors

Song, Li Ting; Liu, Rui Rui; Zhai, Hong Lin; Meng, Ya Jie; Zhu, Min

doi:10.1016/j.abb.2018.12.029

Cited by 4 publications

(2 citation statements)

References 39 publications

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“…To investigate the molecular interaction pattern by which vitexin might exert its antiviral activity, the molecular docking approach was employed. Several molecular targets commonly used for screening small molecules in the field of antiviral drug discovery such as HSV type‐1 DNA polymerase, HSV type‐1 thymidine kinase, HAV 3C proteinase, HBV capsid protein, and HCV protease‐helicase, were exploited for in silico study. A prerequisite to any successful experiment is the validation step.…”

Section: Resultsmentioning

confidence: 99%

Breaking Down the Barriers to a Natural Antiviral Agent: Antiviral Activity and Molecular Docking of Erythrina speciosa Extract, Fractions, and the Major Compound

Fahmy

Al‐Sayed

Moghannem

et al. 2020

Chemistry & Biodiversity

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The in vitro cytotoxic activity in Vero cells and the antiviral activity of Erythrina speciosa methanol extract, fractions, and isolated vitexin were studied. The results revealed that E. speciosa leaves ethyl acetate soluble fraction of the methanol extract (ESLE) was the most active against herpes simplex virus type 1 (HSV‐1). Bioactivity‐guided fractionation was performed on ESLE to isolate the bioactive compounds responsible for this activity. One sub‐fraction from ESLE (ESLE IV) showed the highest activity against HSV‐1 and Hepatitis A HAV‐H10 viruses. Vitexin isolated from ESLE VI exhibited a significant antiviral activity (EC50=35±2.7 and 18±3.3 μg/mL against HAV‐H10 and HSV‐1 virus, respectively), which was notably greater than the activity of the extract and the fractions. Molecular docking studies were carried out to explore the molecular interactions of vitexin with different macromolecular targets. Analysis of the in silico data together with the in vitro studies validated the antiviral activity associated with vitexin. These outcomes indicated that vitexin is a potential candidate to be utilized commendably in lead optimization for the development of antiviral agents.

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Section: Resultsmentioning

confidence: 99%

Breaking Down the Barriers to a Natural Antiviral Agent: Antiviral Activity and Molecular Docking of Erythrina speciosa Extract, Fractions, and the Major Compound

Fahmy

Al‐Sayed

Moghannem

et al. 2020

Chemistry & Biodiversity

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“…Structure modification and SAR led to improved inhibitory efficacy of the sulfamoylbenzamide class compound SBA_R01 (NVR 3-778) (Table 2), which is in phase II clinical trial for the treatment of HBV infection [127]. Similar approaches were used to optimize other compounds; e.g., tetrahydropyrrolopyrimidines based on Bay41_4109 and GLS4 [128], N-phenyl-3sulfamoyl-benzamide derivative inhibiting HBV capsid assembly in vitro [129] (Table 2), or to explain the enhanced binding of heteroaryldihydropyrimidine inhibitor to the Y132A mutant compared to the wild type of the core protein [130]. 4-oxotetrahydropyrimidinederived phenyl urea, compound 27 (58031) (Table 2), and some analogues were shown to inhibit HBV by mistargeting the HBc protein to assemble empty capsids devoid of viral pregenomic RNA in human hepatocytes [131].…”

Section: Hepatitis B Virus Assembly Inhibitorsmentioning

confidence: 99%

Targeting the Virus Capsid as a Tool to Fight RNA Viruses

Hozáková

Vokatá

Ruml

et al. 2022

Viruses

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Several strategies have been developed to fight viral infections, not only in humans but also in animals and plants. Some of them are based on the development of efficient vaccines, to target the virus by developed antibodies, others focus on finding antiviral compounds with activities that inhibit selected virus replication steps. Currently, there is an increasing number of antiviral drugs on the market; however, some have unpleasant side effects, are toxic to cells, or the viruses quickly develop resistance to them. As the current situation shows, the combination of multiple antiviral strategies or the combination of the use of various compounds within one strategy is very important. The most desirable are combinations of drugs that inhibit different steps in the virus life cycle. This is an important issue especially for RNA viruses, which replicate their genomes using error-prone RNA polymerases and rapidly develop mutants resistant to applied antiviral compounds. Here, we focus on compounds targeting viral structural capsid proteins, thereby inhibiting virus assembly or disassembly, virus binding to cellular receptors, or acting by inhibiting other virus replication mechanisms. This review is an update of existing papers on a similar topic, by focusing on the most recent advances in the rapidly evolving research of compounds targeting capsid proteins of RNA viruses.

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