bims-antpol 2024-11-24 papers

Issue of 2024–11–24
four papers selected by
Rick Sheridan, EMSKE Phytochem

Phytomedicine. 2024 Aug 10. pii: S0944-7113(24)00573-7. [Epub ahead of print]135 155915

Mechanism Research of QingReJieDu Formula for Treating Hepatitis B Virus Based on Network Pharmacology.

Caixia Jia, Hongxing Wu, Aiqing Yang, Aiping Chen, Xueting Wang, Shuqin Ding, Baofeng Fan, Gangqiao Zhou, Zhihong Li, Jianxin Chen.

BACKGROUND: Hepatitis B virus (HBV) is a DNA virus known to induce hepatitis and liver dysfunction, and is one of the main causes of liver cirrhosis and liver cancer. At present, there lacks a satisfactory optimal treatment plan for HBV in clinical practice, promoting the development of a novel Chinese formula, QingReJieDu Formula (QRJDF), as a potential solution.
PURPOSE: This study aims to explore the underlying mechanisms of QRJDF in the treatment of Hepatitis B virus (HBV) through a combination of network pharmacology and experimental validation.
METHODS/STUDY DESIGN: HepG2.2.15 cells were used to study the efficacy of QRJDF against HBV in vitro. Entecavir (ETV) was used as a positive control. Additionally, HBV transgenic mice served as subjects to study the in vivo efficacy of QRJDF against HBV, with serum and tissue samples analyzed post-euthanasia at 12 weeks to observe relevant indicators. UPLC-Q-TOF-MS technology was utilized to obtain the main ingredients in QRJDF. Network pharmacology was used to explore the potential ingredients and targets of QRJDF against HBV. Transcriptome sequencing was used to further explore the potential targets of QRJDF against HBV. Finally, integration of network pharmacology and transcriptomics results facilitated the screening of potential key targets and identification of potential pathways.
RESULTS: QRJDF demonstrated anti-HBV effects in HepG2.2.15 cells, compared to ETV control, QRJDF was more efficient in inhibiting HBV antigen levels, although it was less efficient in inhibiting HBV DNA level. In addition, the antiviral effect was verified in HBV transgenic mice. Network pharmacology results found three major active anti-HBV ingredients from QRJDF. Network pharmacology and transcriptomics revealed that QRJDF could act on the TGFβ1/Smad4 signaling pathway.
CONCLUSION: The study comprehensively evaluated the efficacy in vivo and in vitro, and fully confirmed that QRJDF was a potential therapeutic agent for HBV. In addition, the transcriptome technology was verified, and the key targets and approaches of QRJDF against hepatitis B were screened in combination with network pharmacology, which provided research ideas for the follow-up research of antiviral Chinese medicine.

Keywords: Hepatitis B virus; Mechanism; Network pharmacology; QingReJieDu Formula; Transcriptome

DOI: https://doi.org/10.1016/j.phymed.2024.155915

Microbiol Spectr. 2024 Nov 18. e0220024

Etoposide targets 2A protease to inhibit enterovirus 71 replication.

Qinqin Liang, Sai Shi, Qingjie Zhang, Yaxin Wang, Sheng Ye, Binghong Xu.

Enterovirus 71 (EV71) is a major pathogen that causes hand, foot, and mouth disease (HFMD) in infants and children. Notably, no clinically approved drugs specifically target EV71. The EV71 2A protease (2Apro), a cysteine protease produced by the virus, is essential for the virus' replication and has a significant impact on the functioning of host cells. Thus, it presents a valuable target for the discovery of antiviral medications. In this study, based on the monomers and their derivatives in the Library of Traditional Chinese Medicine (TCM), we performed virtual screening and biological experiments. We identified a derivative of a traditional herbal monomer, Etoposide, commonly isolated from the roots and rhizomes of Podophyllum spp. Etoposide inhibited replication of EV71 A, B, C, and CVA16 viruses in a concentration-dependent manner in a variety of cell lines with minimal cytotoxicity. Furthermore, both molecular dynamics simulations and site-directed mutagenesis assays revealed that Etoposide inhibited the activity of the EV71 2A protease by mainly binding to two residues, Y89 and P107. The findings indicate that Etoposide serves as a promising inhibitor of the EV71 2Apro, demonstrating strong antiviral properties and positioning itself as a formidable candidate for clinical trials against EV71.IMPORTANCEWe first used a drug screening approach focused on monomeric compounds and their derivatives from traditional Chinese medicine to identify an EV71 2Apro inhibitor-Etoposide. We then performed biological experiments to validate that Etoposide suppresses the replication of the EV71 virus in a concentration-dependent manner with minimal cytotoxicity to various cell lines. Remarkably, it shows inhibitory activity against EV71 A, B, C, and CVA16, suggesting that Etoposide may be a potential broad-spectrum inhibitor. We revealed a novel mechanism that Etoposide inhibits EV71 proliferation by targeting 2Apro, and the interactions with Y89 and P107 are of great importance. The findings suggest that Etoposide serves as a promising inhibitor of EV71 2Apro, demonstrating significant antiviral properties. It stands out as a strong candidate for broad-spectrum applications in clinical research.

Keywords: EV71; Etoposide; HFMD; antiviral; inhibitor

DOI: https://doi.org/10.1128/spectrum.02200-24

Sci Rep. 2024 11 16. 14(1): 28287

Potential antiviral activity of rhamnocitrin against influenza virus H3N2 by inhibiting cGAS/STING pathway in vitro.

Zexing Chen, Wanqi Wang, Kefeng Zeng, Jinyi Zhu, Xinhua Wang, Wanyi Huang.

Influenza remains a serious issue for public health and it's urgent to discover more effected drugs against influenza virus. Rhamnocitrin, as a flavonoid, its effect on influenza virus infection remains poorly explored. In this study, rhamnocitrin showed antiviral effect and anti-apoptosis on influenza virus A/Aichi/2/1968 (H3N2) in MDCK cells and A549 cells. In addition, molecular docking revealed that rhamnocitrin have good binding activity with the target proteins cGAS and STING, molecular dynamic simulation and surface plasmon resonance showed that rhamnocitrin could form a stable complex with the above proteins. Moreover, the qPCR and western blot assays further verified that rhamnocitrin could reduce type I IFN and proinflammatory cytokines production by inhibiting the cGAS/STING pathway. Taken together, the results suggest that rhamnocitrin could be a potential anti-viral agent against influenza.

Keywords: Anti-viral; Apoptosis; Influenza; Rhamnocitrin; STING; cGAS

DOI: https://doi.org/10.1038/s41598-024-79788-z

Heliyon. 2024 Nov 15. 10(21): e39635

Prospects of Carica papaya in the treatment of human viral infections: A comprehensive and a systematic review.

Masooma, Ariba Qaiser, Dr Sajid Ali, Dr Sobia Manzoor.

Background: Viruses cause various human diseases, some of which become pandemic outbreaks lack effective treatments and vaccines. This study gathered data on Carica papaya's antiviral effects against various human viruses, highlighting its potential as a natural treatment. Through in-vitro, in-vivo, and clinical study analysis, we illustrated the potential of Carica papaya in combating viral infections and its potential role in cure of common viral diseases.
Method: ology: Research papers on antiviral activity of Carica papaya were identified by using specific keywords in PUBMED, Google Scholar, and ScienceDirect databases. Articles published between January 2015 and March 2024 were screened for inclusion. Eligible studies utilized Carica papaya leaves (powder or juice) or fruits to investigate their effects against human viral infections. Each selected study applied either qualitative or quantitative antiviral assays to assess the efficacy of Carica papaya in combating human viruses.
Results: Fifteen studies went through assessment for antiviral properties of Carica papaya, 7 (46.67 %) of them displayed significant activity against the dengue virus, while 1 study (6.67 %) demonstrated moderate/less effectiveness against dengue serotype-2. Two studies (13.33 %) found no anti-dengue effects. Additionally, Carica papaya exhibited strong antiviral activity against SARS-CoV-2 in 2 studies (13.33 %). One study (6.67 %) showed inhibition of both dengue serotype-2 and chikungunya, and 1 study (6.67 %) each demonstrated inhibitory effects against human immunodeficiency virus and Zika virus infections.
Conclusion: The present study listed human diseases for which Carica papaya revealed significant antiviral effects against Dengue virus, Severe acute respiratory syndrome, Human immunodeficiency virus-I, Chikungunya virus and Zika virus suggesting its potential as a treatment candidate for all these viruses. However, the majority of the research involved in-vitro screening, with minimal in-vivo and clinical testing. Further in-vivo studies and clinical trials should be conducted to explore the potential of Carica papaya in the treatment of human viral infections.

Keywords: Anti dengue; Antiviral agent; Carica papaya extract; Fruits; Leaves; Virus titer; Viruses

DOI: https://doi.org/10.1016/j.heliyon.2024.e39635