Current theories of pathophysiology and potential therapeutic targets of COVID-19: What we know so far

In 2019, a new variant of coronavirus emerged that put the whole world on a standstill due to its unprecedented spread and morbidity. Since then, scientists have been working on several theories to explain the origin and pathogenesis of the virus. Over this period of time, it has been observed clinically that individual variation exists in the way this virus infects people, its symptomatology and sequelae. The pathophysiology is still unclear. This review was taken up to consolidate all the available information until date about current theories of etiopathogenesis with an understanding of potential therapeutic targets on the mechanisms. This review also highlights the gray areas that need to be addressed in the future. Research papers published up to December 7, 2020 were included based on a search on PubMed, Google Scholar, etc., to get the latest relevant literature on this topic. Coronavirus expresses differently in different individuals, affecting different organ systems, and having variable severity. However, the underlying pathogenic mechanisms are not completely understood. Due to the lack of definite curative therapy, it is essential to explore the basic pathophysiology so as to develop more effective and target-based therapies in the future.

Computational identification of maize miRNA and their gene targets involved in biotic and abiotic stresses

Plant interactions with biotic and abiotic stresses are complex and entail changes at the transcriptional, cellularand physiological level. MicroRNAs (miRNAs) are small (*20–24 nt), non-coding RNAs that play a vital rolein wide range of biological processes involved in regulation of gene expression through translation inhibitionor degradation of their target mRNAs during stress conditions. Therefore, identification of miRNAs and theirtargets are of immense value in understanding the regulatory networks triggered during stress. Advancement incomputational approaches has opened up ways for the prediction of miRNAs and their possible targets withfunctional pathways. Our objective was to identify miRNA and their potential targets involved in both bioticand abiotic stresses in maize. A total of 2,019,524 downloaded ESTs from dbEST were processed and trimmedby Seq Clean. The program trashed 264,000 and trimmed 284,979 sequences and the resulting 1,755,534sequences were submitted for clustering and assembled to RepeatMasker and TGICL. A total of 30 miRNAswere found to hybridize with the potential targets of gene families such as CoA ligase, lipoxygenase 1,Terpenoideyclases, Zn finger, transducing, etc. Ten of the identified miRNAs targeted cytochrome c1 family.Zm_miR23 class targeted 11 different genes. The identified targets are involved in the plant growth anddevelopment during biotic and abiotic stresses in maize. These miRNAs may be further used for functionalanalysis. Furthermore, four and two of the miRNA targets were validated in response to waterlogging toleranceand southern leaf blight resistance, respectively, to understand the miRNA-assisted regulation of targetmiRNAs. The functional annotation of the predicted targets indicated that these stress-responsive miRNAsregulate cellular function; molecular function and biological process in maize at the post-transcriptional level.The present results have paved way towards better understanding the role of miRNAs in the mechanism ofstress tolerance in maize.

Study on therapeutic mechanism of Rehmanniae Radix Praeparata- Corni Fructus in sequelae of ischemic stroke based on network pharmacology technology / 中国中药杂志

In ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair has the effect in protecting damaged neurons, but its mechanism has not been clear. In this study, network pharmacology was used to predict the mechanism of Rehmanniae Radix Praeparata-Corni Fructus in the treatment of ischemic stroke sequela. Through database search and literature retrie-val, 40 active ingredients of Rehmanniae Radix Praeparata and Corni Fructus were obtained, and their targets were obtained through STITCH and TCMSP databases. The targets of ischemic stroke sequela were obtained through OMIM,GAD,TTD and DrugBank databases. By screening the intersections of active ingredients targets and stroke treatment targets, 21 potential targets were obtained. The DAVID database was used for GO enrichment analysis and KEGG pathway analysis of potential targets. GO enrichment analysis showed that Rehmanniae Radix Praeparata-Corni Fructus were mainly involved in regulation of blood pressure, negative regulation of extrinsic apoptotic signaling and positive regulation of angiogenesis. KEGG pathway analysis showed that Rehmanniae Radix Praeparata-Corni Fructus could inhibit inflammatory response and apoptosis signaling pathway by regulating HIF-VEGFA signaling pathway in neural stem cell proliferation, TNF signaling pathway and NF-kappaB signaling pathway. Molecular docking technique was used to verify that Rehmanniae Radix Praeparata-Corni Fructus component has a good binding activity with potential targets. The results showed that in ischemic stroke sequela phase, Rehmanniae Radix Praeparata-Corni Fructus drug pair could play an important role in recovering neural function, promoting the proliferation of neural stem cells, angiogenesis, preventing neural cells apoptosis and regulating inflammatory factors.

Mechanism of Modified Taohe Chengqitang in Treating Type 2 Diabetes Mellitus Based on Network Pharmacology / 中国实验方剂学杂志

Objective: To study the potential therapeutic targets of modified Taohe Chengqitang for type 2 diabetes mellitus based on network pharmacology. Method: Based on TCMSP database and Uniprot database, the active constituents and target genes of flavored modified Taohe Chengqitang were screened.Target genes of type 2 diabetes were screened by gene cards database and OMIM database, and Cytoscape software was used to construct " active component-target" interaction network diagram.The active component targets and disease targets were uploaded to the STRING database, the protein interaction network map (PPI) was constructed, and the characteristic values were calculated, and core genes were screened by using R language.Finally, R language was used to analyze gene ontology (GO) enrichment and kyoto encyclopedia of genes and genome (KEGG) pathway enrichment of key targets. Result: The 155 active components and 106 effective targets of modified Taohe Chengqitangin the treatment of type 2 diabetes were predicted.Quercetin, kaempferol and isorhamnetin were the most effective components, while estrogen receptor alpha (ESR1), peroxidosomal hyperplasia activates receptor gamma (PPARG) and androgen receptor (AR) were the most effective components.Core genes in PPI network areepidermal growth factor receptor (EGFR)and ESR1, etc.GO enrichment analysis shows that it can affect gene transcription, nuclear receptor activity, hormone receptor binding, neurotransmitter, etc.Enrichment analysis of KEGG pathway showed that fluid shear stress and atherosclerosis pathways were the most significant pathways, followed by advanced glycation end products-receptor for AGE (AGE-RAGE) pathway. Conclusion: Predicted by the method of network pharmacology modified Taohe Chengqitang key targets for prevention and treatment of type 2 diabetes and related pathways, results suggest the recipe has multiple targets, multiple pathways, such as complex mechanism, not only show that modified Taohe Chengqitang has hypoglycemic effect, but it also has anti-inflammatory, improve insulin resistance, regulate lipid metabolism, and biological functions.

Active compounds from Baoyuan decoction with myocardial protection activities and their potential targets / 中国中药杂志

Baoyuan decoction (BYD) is a classical Chinese formula for coronary heart disease with Qi deficiency, blood stasis tonifying Qi and Yang deficiency. However, the chemical material basis and underlying action mechanisms of BYD still lack systemic study. In order to clarify the active compounds and the potential action mechanisms of BYD, the oxygen-glucose deprivation/recovery (OGD/R)-induced H9c2 cells injury models was used to screen the monomeric compounds of BYD with myocardial protection activity. PubChem's BioAssay database was then used to analyze the potential targets of active monomeric compounds, classify the predicted biological targets, and analyze the internal relation between active compounds of BYD and biological targets. The screening results showed that BYD aqueous extract and 17 monomeric compounds could significantly increase the survival rate of OGD/R-induced H9c2 myocardial cells. The results of virtual targets screening study showed that 15 monomeric compounds and the potential mechanisms for myocardial protection were related to oxidative stress pathway, calcium ion pathway, mitochondrial protection, anti-apoptosis, etc. These results verified that BYD had myocardial protection effect, which was obtained by network regulation of multi-components and multi-targets. All these results provide the theoretical basis and references for the clinical usage of BYD in treatment of coronary heart disease.