COVID-19 is threatening human health worldwide but no effective treatment currently exists for this disease. Current therapeutic strategies focus on the inhibition of viral replication or using anti-inflammatory/immunomodulatory compounds to improve host immunity, but not both. Traditional Chinese medicine (TCM) compounds could be promising candidates due to their safety and minimal toxicity. In this study, we have developed a novel in silico bioinformatics workflow that integrates multiple databases to predict the use of honeysuckle (Lonicera japonica) and Huangqi (Astragalus membranaceus) as potential anti-SARS-CoV-2 agents. Using extracts from honeysuckle and Huangqi, these two herbs upregulated a group of microRNAs including let-7a, miR-148b, and miR-146a, which are critical to reduce the pathogenesis of SARS-CoV-2. Moreover, these herbs suppressed pro-inflammatory cytokines including IL-6 or TNF-α, which were both identified in the cytokine storm of acute respiratory distress syndrome, a major cause of COVID-19 death. Furthermore, both herbs partially inhibited the fusion of SARS-CoV-2 spike protein-transfected BHK-21 cells with the human lung cancer cell line Calu-3 that was expressing ACE2 receptors. These herbs inhibited SARS-CoV-2 M^pro activity, thereby alleviating viral entry as well as replication. In conclusion, our findings demonstrate that honeysuckle and Huangqi have the potential to be used as an inhibitor of SARS-CoV-2 virus entry that warrants further in vivo analysis and functional assessment of miRNAs to confirm their clinical importance. This fast-screening platform can also be applied to other drug discovery studies for other infectious diseases.

Metabolism consists of diverse life‐sustaining chemical reactions in living organisms. Autophagy is a highly conservative process that responds to various internal and external stresses. Both processes utilize surrounding resources to provide energy and nutrients for the cell. Autophagy progression may proceed to the degradative or secretory pathway determined by Rab family proteins. The former is a degradative and lysosome‐dependent catabolic process that produces energy and provides nutrients for the synthesis of essential proteins. The degradative pathway also balances the energy source of the cell and regulates tissue homeostasis. The latter is a newly discovered pathway in which the autophagosome is fused with the plasma membrane. Secretory autophagy participates in diverse functions and diseases ranging from the spread of viral particles to cancer and neurodegenerative diseases. Aberrant metabolism in the body causes various metabolic syndromes. This review explores the relationships among autophagy, metabolism, and related diseases.

High blood glucose is one of the risk factors for metabolic disease and INS (insulin) is the key regulatory hormone for glucose homeostasis. Hypoinsulinemia accompanied with hyperglycemia was diagnosed in mice with pancreatic β-cells exhibiting autophagy deficiency; however, the underlying mechanism remains elusive. The role of secretory autophagy in the regulation of metabolic syndrome is gaining more attention. Our data demonstrated that increased macroautophagic/autophagic activity leads to induction of insulin secretion in β-cells both in vivo and in vitro under high-glucose conditions. Moreover, proteomic analysis of purified autophagosomes from β-cells identified a group of vesicular transport proteins participating in insulin secretion, implying that secretory autophagy regulates insulin exocytosis. RAB37, a small GTPase, regulates vesicle biogenesis, trafficking, and cargo release. We demonstrated that the active form of RAB37 increased MAP1LC3/LC3 lipidation (LC3-II) and is essential for the promotion of insulin secretion by autophagy, but these phenomena were not observed in rab37 knockout (rab37^-/-) cells and mice. Unbalanced insulin and glucose concentration in the blood was improved by manipulating autophagic activity using a novel autophagy inducer niclosamide (an antihelminthic drug) in a high-fat diet (HFD)-obesity mouse model. In summary, we reveal that secretory autophagy promotes RAB37-mediated insulin secretion to maintain the homeostasis of insulin and glucose both in vitro and in vivo.

Increasing lines of evidence indicate that the biologically active form of vitamin D, calcitriol (1,25-dihydroxyvitamin D₃), prevents cancer progression by reducing cell proliferation, increasing cell differentiation, and inhibiting angiogenesis, among other potential roles. Cancer cells in solid tumors preferably undergo the “Warburg effect” to support cell growth by upregulating glycolysis, and the glycolytic intermediates further serve as building blocks to generate biomass. The objective of the current study is to investigate whether calcitriol affects glucose metabolism and cell growth in human colorectal cancer cells. Calcitriol reduced the expression of cyclin D1 and c-Myc. In addition, calcitriol reduced the expression of glucose transporter 1 (GLUT1) and key glycolytic enzymes and decreased extracellular acidification rate but increased oxygen consumption rate in human colorectal cancer cells. In a subcutaneous HT29 xenograft NOD/SCID mouse model, the volume and weight of the tumors were smaller in the calcitriol groups as compared with the control group, and the expression levels of GLUT1 and glycolytic enzymes, hexokinase 2 and lactate dehydrogenase A, were also lower in the calcitriol groups in a dose-responsive manner. Our data indicate that calcitriol suppresses glycolysis and cell growth in human colorectal cancer cells, suggesting an inhibitory role of the biologically active form of vitamin D in colorectal cancer progression.

We previously reported that dengue virus (DENV)‐induced autophagy plays a promoting role in viral replication and pathogenesis both in vitro and in vivo. Although it is known that DENV infection increases glycolysis, which promotes viral replication, the role of glucose metabolism together with autophagic activity in DENV replication remains unclear. In this study, we reveal that DENV2 infection increased autophagic activity, glucose uptake, protein levels of glucose transporter‐1 (GLUT1), and glycolysis rate‐limiting enzyme hexokinase‐2 (HK2) in cells. Furthermore, the protein levels of LC3‐II and HK2 were increased in the brain tissues of the DENV2‐infected suckling mice. However, DENV2 infection decreased ATP level and showed no effect on mRNA expression of HK2 and phosphofructokinase, as well as lactate production, indicating that DENV2‐regulated glycolytic flux occurs at the post‐transcriptional level and is lactate pathway‐independent. Moreover, amiodarone‐induced autophagic activity, glucose uptake, HK2 level, and viral titer were reversed by the autophagy inhibitor spautin‐1 or silencing of Atg5 gene expression. Intriguingly, blocking of glycolysis, HK2 protein level, and viral titer were accordingly decreased, but autophagic activity was increased, suggesting the existence of another regulation mechanism that influences the relationship between glycolysis and autophagy. This is the first report to reveal that DENV2‐induced autophagy positively regulates glycolysis and viral replication in vitro and in vivo. Our findings open a new avenue wherein metabolic modulation could be used as a target for the treatment of DENV infection.