Background: Computer-assisted drug virtual screening models the process of drug screening through computer simulation technology, by docking small molecules in some of the databases to a certain protein target. There are many kinds of small molecules databases available for drug screening, including natural product databases.Methods: Plants have been used as a source of medication for millennia. About 80% of drugs were either natural products or related analogues by 1990, and many natural products are biologically active and have favorable absorption, distribution, metabolization, excretion, and toxicology.Results: In this paper, we review the natural product databases’ contributions to drug discovery based on virtual screening, focusing particularly on the introductions of plant natural products, microorganism natural product, Traditional Chinese medicine databases, as well as natural product toxicity prediction databases.Conclusion: We highlight the applications of these databases in many fields of virtual screening, and attempt to forecast the importance of the natural product database in next-generation drug discovery.

Crystal-cell interactions are a vital step toward kidney stone formation. However, its mechanisms remained unclear. Here, a protein-protein interaction (PPI) network analysis of a kidney stone revealed that the proteins were enriched in a posttranslational protein modification process in the endoplasmic reticulum (ER). Thein vitrostudy showed that the markers of ER stress, including Bip and CHOP, were upregulated, PERK and ATF6 were activated, and XBP-1 mRNA was spliced. An ER stress-specific protein, caspase-12, was activated in the apoptotic cells induced by calcium oxalate monohydrate (COM) crystals. The treatment with tunicamycin, an ER stress inducer, promoted the crystal-cell adhesion assayed by atomic absorption, reduced cell viability assayed by MTT, and downregulated the expression of proteins involved in the crystal formations. The treatment with salubrinal, an ER stress inhibitor, reversed the above effects for both tunicamycin and COM crystals. The aforementioned main observations were supported byin vivostudy. These data demonstrated that ER stress was an essentially biological process of crystal-cell interactions. Our findings suggest that blocking ER stress may become a potential approach to preventing a kidney stone.

Existing evidence has demonstrated liposomes as the gene transporter induce the cytotoxicity during the transfection process through several known pathways. In the present study, we investigated the possibility of siRNAs targeting 3-β-hydroxysterol △-24-reductase (DHCR24), which encodes an enzyme catalyzing the last step of cholesterol biosynthesis, to suppress the liposome cytotoxicity induced by lipid-based transfection reagent in the neuroblastoma cell line N2A. We found that the siRNAs targeting DHCR24 mRNA protect cells from the liposome-induced cell death, probably through the effect of siDHCR24s on the reduction of the cellular cholesterol and decrease in the generation of reactive oxygen species (ROS). This suggests that siRNAs targeting DHCR24 or other methods that reduce the intracellular cholesterol levels might be a good strategy for avoiding the cytotoxicity of liposomes, without impairing its efficiency of gene-delivering.

Since the outbreak of the novel Corona Virus Disease 2019 (COVID-19) infected by SARS-CoV-2 at the end of 2019, clinical specific antiviral drugs have been lacking. A Chinese patent medicine called ‘Toujiequwen Granules’ has been promoted in the treatment of COVID-19. The present study was designed to reveal the molecular mechanism of Toujiequwen Granules against COVID-19. A network pharmacological method was applied to screen the main active ingredients of Tongjiequwen Granules. Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredients interacting with many drug targets are quercetin., drug targets most affected by the active ingredients are PTGS2, PTGS1, and DPP4. Drug target disease enrichment analysis showed drug targets are significantly enriched in cardiovascular diseases, digestive tract diseases and so forth. An ‘active ingredient-target-disease’ network showed that 57 active ingredients from Toujiequwen Granules, interact with 15 key targets of coronary pneumonia. There are 53 ingredients that can act on DPP4, suggesting that DPP4 may become a potential new key target for the treatment of COVID-19. The GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide, cytokine activity and other functions. KEGG analysis showed they were mainly concentrated in viral protein interaction with cytokine and cytokine receptors endocrine resistance pathway, and others. These evidences suggest that Toujiequwen Granules might play an effective role through improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against multiple signaling pathways related to the pathogenesis of SARS-CoV-2.