Identification of berberine as a potential therapeutic strategy for kidney clear cell carcinoma and COVID-19 based on analysis of large-scale datasets.

Background: Regarding the global coronavirus disease 2019 (COVID)-19 pandemic, kidney clear cell carcinoma (KIRC) has acquired a higher infection probability and may induce fatal complications and death following COVID-19 infection. However, effective treatment strategies remain unavailable. Berberine exhibits significant antiviral and antitumour effects. Thus, this study aimed to provide a promising and reliable therapeutic strategy for clinical decision-making by exploring the therapeutic mechanism of berberine against KIRC/COVID-19. Methods: Based on large-scale data analysis, the target genes, clinical risk, and immune and pharmacological mechanisms of berberine against KIRC/COVID-19 were systematically investigated. Results: In total, 1,038 and 12,992 differentially expressed genes (DEGs) of COVID-19 and KIRC, respectively, were verified from Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively, and 489 berberine target genes were obtained from official websites. After intersecting, 26 genes were considered potential berberine therapeutic targets for KIRC/COVID-19. Berberine mechanism of action against KIRC/COVID-19 was revealed by protein-protein interaction, gene ontology, and Kyoto Encyclopedia of Genes and Genomes with terms including protein interaction, cell proliferation, viral carcinogenesis, and the PI3K/Akt signalling pathway. In COVID-19 patients, ACOX1, LRRK2, MMP8, SLC1A3, CPT1A, H2AC11, H4C8, and SLC1A3 were closely related to disease severity, and the general survival of KIRC patients was closely related to ACOX1, APP, CPT1A, PLK1, and TYMS. Additionally, the risk signature accurately and sensitively depicted the overall survival and patient survival status for KIRC. Numerous neutrophils were enriched in the immune system of COVID-19 patients, and the lives of KIRC patients were endangered due to significant immune cell infiltration. Molecular docking studies indicated that berberine binds strongly to target proteins. Conclusion: This study demonstrated berberine as a potential treatment option in pharmacological, immunological, and clinical practice. Moreover, its therapeutic effects may provide potential and reliable treatment options for patients with KIRC/COVID-19.

Potential therapeutic strategies for quercetin targeting critical pathological mechanisms associated with colon adenocarcinoma and COVID-19

Patients with colon adenocarcinoma (COAD) are at a higher probability of infection with COVID-19 than healthy individuals. However, there is no globally accepted treatment protocol for patients with COAD/COVID-19. Quercetin has been found to have significant antitumor, antiviral and anti-inflammatory effects in several studies. Therefore, this study sought to evaluate the potential of quercetin as the agent for COAD/COVID-19 and to explore its mechanisms. We used bioinformatics algorithms to obtain COAD/COVID-19-related genes (CCRG) from COAD-related transcriptome data and COVID-related transcriptome sequencing data, and used these genes to construct a COAD prognostic model. We intersected the CCRG with the therapeutic target genes of quercetin and obtained a total of 105 genes (potential target genes of quercetin for the treatment of COAD/COVID-19). By constructing a protein-protein interaction (PPI) network, we ascertained FOS, NFKB1, NFKB1A, JUNB, and JUN as possible core target genes of quercetin for the treatment of COAD/COVID-19. Bioinformatic analysis of these 105 genes revealed that the mechanisms for quercetin the treatment of COAD/COVID-19 may be associated with oxidative stress, apoptosis, anti-inflammatory, immune, anti-viral and multiple pathways containing IL-17, TNF, HIF-1. In this study, we constructed a prognostic model of COAD/COVID19 patients by using CCRG and elucidated for the first time the potential target genes and molecular mechanisms of quercetin for the treatment of COAD/COVID-19, which may benefit the clinical treatment of COAD/COVID-19 patients. However, no clinical trials have yet been conducted to further validate the findings, but this will be the future direction of our research.

When 3D genome technology meets viral infection, including SARS-CoV-2.

Mammalian chromosomes undergo varying degrees of compression to form three-dimensional genome structures. These three-dimensional structures undergo dynamic and precise chromatin interactions to achieve precise spatial and temporal regulation of gene expression. Most eukaryotic DNA viruses can invade their genomes into the nucleus. However, it is still poorly understood how the viral genome is precisely positioned after entering the host cell nucleus to find the most suitable location and whether it can specifically interact with the host genome to hijack the host transcriptional factories or even integrate into the host genome to complete its transcription and replication rapidly. Chromosome conformation capture technology can reveal long-range chromatin interactions between different chromosomal sites in the nucleus, potentially providing a reference for viral DNA-host chromatin interactions. This review summarized the research progress on the three-dimensional interaction between virus and host genome and the impact of virus integration into the host genome on gene transcription regulation, aiming to provide new insights into chromatin interaction and viral gene transcription regulation, laying the foundation for the treatment of infectious diseases.

Puerarin: A Potential Therapeutic for Colon Adenocarcinoma (COAD) Patients Suffering From SARS-CoV-2 Infection.

Patients with colonic adenocarcinoma (COAD) are at relatively high risk of SARS-CoV-2 infection. However, there is a lack of medical strategies to treat COVID-19/COAD comorbidity. Puerarin, a natural product, is a known antiviral, antitumor, and immunomodulatory effect. Therefore, we hypothesised that puerarin could be used to treat COVID-19/COAD patients. Based on network pharmacology and bioinformatics analysis, the potential targets and pharmacological mechanisms of puerarin in COVID-19/COAD were identified. By intersecting therapeutic target genes for puerarin, COVID-19-related genes and COAD-related genes, 42 target genes of puerarin that could potentially treat COVID-19/COAD comorbidity were obtained. By using the 42 potential target genes to construct the protein-protein interaction (PPI) network, we obtained five core target genes, namely RELA, BCL2, JUN, FOS, and MAPK1. The results of bioinformatics analysis revealed that puerarin could be able to treat COVID-19/COAD comorbidity through apoptosis, antiviral, antioxidant, NF-κB signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and HIF-1 signaling pathway etc. This study found that puerarin has the potential to treat COVID-19/COAD patients and that the therapeutic target genes obtained in the study may provide clues for the treatment of COVID19/COAD comorbidity.

Puerarin: A Potential Therapeutic for SARS-CoV-2 and Hantavirus Co-Infection.

Patients with Hantavirus-caused epidemic hemorrhagic fever (EHF) are at risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is currently no validated EHF/SARS-CoV-2 strategy. Several studies have recently shown Puerarin, a natural product, has potent antiviral properties. The goal of present study was to determine the mechanism of puerarin in patients with EHF/COVID-19. We use network pharmacology and bioinformatics to investigate the possible pharmacological targets, bioactivities, and molecular mechanisms of puerarin in the treatment of patients with EHF/SARS-CoV-2. The study investigated the pathogenesis of COVID-19 and EHF and the signaling pathway impacted by puerarin. 68 common genes linked to puerarin and EHF/SARS-CoV-2 were discovered during the investigation. By using protein-protein interaction (PPI) network, we identified RELA, JUN, NF-B1, NF-B2, and FOS as potential therapeutic targets. The bioactivity and signaling pathways of puerarin have also been demonstrated in the treatment of EHF and COVID-19. According to present study, puerarin could reduce excessive immune responses and inflammation through the NF-B, TNF, and HIF-1 signaling pathways. This study explored the potential therapeutic targets and mechanisms of Puerarin in the treatment of EHF/COVID-19.