RVvictor: Virus RNA-directed molecular interactions for RNA virus infection.

RNA viruses are major human pathogens that cause seasonal epidemics and occasional pandemic outbreaks. Due to the nature of their RNA genomes, it is anticipated that virus's RNA interacts with host protein (INTPRO), messenger RNA (INTmRNA), and non-coding RNA (INTncRNA) to perform their particular functions during their transcription and replication. In other words, thus, it is urgently needed to have such valuable data on virus RNA-directed molecular interactions (especially INTPROs), which are highly anticipated to attract broad research interests in the fields of RNA virus translation and replication. In this study, a new database was constructed to describe the virus RNA-directed interaction (INTPRO, INTmRNA, INTncRNA) for RNA virus (RVvictor). This database is unique in a) unambiguously characterizing the interactions between viruses RNAs and host proteins, b) providing, for the first time, the most systematic RNA-directed interaction data resources in providing clues to understand the molecular mechanisms of RNA viruses' translation, and replication, and c) in RVvictor, comprehensive enrichment analysis is conducted for each virus RNA based on its associated target genes/proteins, and the enrichment results were explicitly illustrated using various graphs. We found significant enrichment of a suite of pathways related to infection, translation, and replication, e.g., HIV infection, coronavirus disease, regulation of viral genome replication, and so on. Due to the devastating and persistent threat posed by the RNA virus, RVvictor constructed, for the first time, a possible network of cross-talk in RNA-directed interaction, which may ultimately explain the pathogenicity of RNA virus infection. The knowledge base might help develop new anti-viral therapeutic targets in the future. It's now free and publicly accessible at: https://idrblab.org/rvvictor/.

RNAenrich: a web server for non-coding RNA enrichment.

MOTIVATION: With the rapid advances of RNA sequencing and microarray technologies in non-coding RNA (ncRNA) research, functional tools that perform enrichment analysis for ncRNAs are needed. On the one hand, because of the rapidly growing interest in circRNAs, snoRNAs, and piRNAs, it is essential to develop tools for enrichment analysis for these newly emerged ncRNAs. On the other hand, due to the key role of ncRNAs' interacting target in the determination of their function, the interactions between ncRNA and its corresponding target should be fully considered in functional enrichment. Based on the ncRNA-mRNA/protein-function strategy, some tools have been developed to functionally analyze a single type of ncRNA (the majority focuses on miRNA); in addition, some tools adopt predicted target data and lead to only low-confidence results. RESULTS: Herein, an online tool named RNAenrich was developed to enable the comprehensive and accurate enrichment analysis of ncRNAs. It is unique in (i) realizing the enrichment analysis for various RNA types in humans and mice, such as miRNA, lncRNA, circRNA, snoRNA, piRNA, and mRNA; (ii) extending the analysis by introducing millions of experimentally validated data of RNA-target interactions as a built-in database; and (iii) providing a comprehensive interacting network among various ncRNAs and targets to facilitate the mechanistic study of ncRNA function. Importantly, RNAenrich led to a more comprehensive and accurate enrichment analysis in a COVID-19-related miRNA case, which was largely attributed to its coverage of comprehensive ncRNA-target interactions. AVAILABILITY AND IMPLEMENTATION: RNAenrich is now freely accessible at https://idrblab.org/rnaenr/.

CovInter: interaction data between coronavirus RNAs and host proteins.

Coronavirus has brought about three massive outbreaks in the past two decades. Each step of its life cycle invariably depends on the interactions among virus and host molecules. The interaction between virus RNA and host protein (IVRHP) is unique compared to other virus-host molecular interactions and represents not only an attempt by viruses to promote their translation/replication, but also the host's endeavor to combat viral pathogenicity. In other words, there is an urgent need to develop a database for providing such IVRHP data. In this study, a new database was therefore constructed to describe the interactions between coronavirus RNAs and host proteins (CovInter). This database is unique in (a) unambiguously characterizing the interactions between virus RNA and host protein, (b) comprehensively providing experimentally validated biological function for hundreds of host proteins key in viral infection and (c) systematically quantifying the differential expression patterns (before and after infection) of these key proteins. Given the devastating and persistent threat of coronaviruses, CovInter is highly expected to fill the gap in the whole process of the 'molecular arms race' between viruses and their hosts, which will then aid in the discovery of new antiviral therapies. It's now free and publicly accessible at: https://idrblab.org/covinter/.

REGLIV: Molecular regulation data of diverse living systems facilitating current multiomics research.

Multiomics is a powerful technique in molecular biology that facilitates the identification of new associations among different molecules (genes, proteins & metabolites). It has attracted tremendous research interest from the scientists worldwide and has led to an explosive number of published studies. Most of these studies are based on the regulation data provided in available databases. Therefore, it is essential to have molecular regulation data that are strictly validated in the living systems of various cell lines and in vivo models. However, no database has been developed yet to provide comprehensive molecular regulation information validated by living systems. Herein, a new database, Molecular Regulation Data of Living System Facilitating Multiomics Study (REGLIV) is introduced to describe various types of molecular regulation tested by the living systems. (1) A total of 2996 regulations describe the changes in 1109 metabolites triggered by alterations in 284 genes or proteins, and (2) 1179 regulations describe the variations in 926 proteins induced by 125 endogenous metabolites. Overall, REGLIV is unique in (a) providing the molecular regulation of a clearly defined regulatory direction other than simple correlation, (b) focusing on molecular regulations that are validated in a living system not simply in an in vitro test, and (c) describing the disease/tissue/species specific property underlying each regulation. Therefore, REGLIV has important implications for the future practice of not only multiomics, but also other fields relevant to molecular regulation. REGLIV is freely accessible at: https://idrblab.org/regliv/.

RNA-RNA interactions between SARS-CoV-2 and host benefit viral development and evolution during COVID-19 infection.

Some studies reported that genomic RNA of SARS-CoV-2 can absorb a few host miRNAs that regulate immune-related genes and then deprive their function. In this perspective, we conjecture that the absorption of the SARS-CoV-2 genome to host miRNAs is not a coincidence, which may be an indispensable approach leading to viral survival and development in host. In our study, we collected five datasets of miRNAs that were predicted to interact with the genome of SARS-CoV-2. The targets of these miRNAs in the five groups were consistently enriched immune-related pathways and virus-infectious diseases. Interestingly, the five datasets shared no one miRNA but their targets shared 168 genes. The signaling pathway enrichment of 168 shared targets implied an unbalanced immune response that the most of interleukin signaling pathways and none of the interferon signaling pathways were significantly different. Protein-protein interaction (PPI) network using the shared targets showed that PPI pairs, including IL6-IL6R, were related to the process of SARS-CoV-2 infection and pathogenesis. In addition, we found that SARS-CoV-2 absorption to host miRNA could benefit two popular mutant strains for more infectivity and pathogenicity. Conclusively, our results suggest that genomic RNA absorption to host miRNAs may be a vital approach by which SARS-CoV-2 disturbs the host immune system and infects host cells.

EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by infection with the larvae of Echinococcus granulosus sensu lato (s.l.) cluster. It is urgent to identify novel drug targets and develop new drug candidates against CE. Glucose transporter 1 (GLUT1) is mainly responsible for the transmembrane transport of glucose to maintain its constant cellular availability and is a recent research hotspot as a drug target in various diseases. However, the role of GLUT1 in E. granulosus s.l. (EgGLUT1) was unknown. In this study, we cloned a conserved GLUT1 homology gene (named EgGLUT1-ss) from E. granulosus sensu stricto (s.s.) and found EgGLUT1-ss was crucial for glucose uptake and viability by the protoscoleces of E. granulosus s.s. WZB117, a GLUT1 inhibitor, inhibited glucose uptake by E. granulosus s.s. and the viability of the metacestode in vitro. In addition, WZB117 showed significant therapeutic activity in E. granulosus s.s.-infected mice: a 10 mg/kg dose of WZB117 significantly reduced the number and weight of parasite cysts (P < 0.05) as efficiently as the reference drug, albendazole. Our results demonstrate that EgGLUT1-ss is crucial for glucose uptake by the protoscoleces of E. granulosus s.s., and its inhibitor WZB117 has a therapeutic effect on CE.

The miRNA: a small but powerful RNA for COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a severe and rapidly evolving epidemic. Now, although a few drugs and vaccines have been proved for its treatment and prevention, little systematic comments are made to explain its susceptibility to humans. A few scattered studies used bioinformatics methods to explore the role of microRNA (miRNA) in COVID-19 infection. Combining these timely reports and previous studies about virus and miRNA, we comb through the available clues and seemingly make the perspective reasonable that the COVID-19 cleverly exploits the interplay between the small miRNA and other biomolecules to avoid being effectively recognized and attacked from host immune protection as well to deactivate functional genes that are crucial for immune system. In detail, SARS-CoV-2 can be regarded as a sponge to adsorb host immune-related miRNA, which forces host fall into dysfunction status of immune system. Besides, SARS-CoV-2 encodes its own miRNAs, which can enter host cell and are not perceived by the host's immune system, subsequently targeting host function genes to cause illnesses. Therefore, this article presents a reasonable viewpoint that the miRNA-based interplays between the host and SARS-CoV-2 may be the primary cause that SARS-CoV-2 accesses and attacks the host cells.

Tacrolimus, a rapamycin target protein inhibitor, exerts anti-cystic echinococcosis effects both in vitro and in vivo.

In view of a growing need for new treatment options for human cystic echinococcosis (CE), we aimed to investigate the efficacy of mTOR pathway inhibitors against CE in vitro and in vivo. Among the seven mTOR inhibitors evaluated, tacrolimus (TAC) showed significant dose- and time-dependent killing of cultured protoscoleces and cysts in vitro. Notably, the oral administration of TAC (4 mg/kg/day) to CE mice model highly effectively reduced both the weight and number of parasitic cysts. Transmission electron microscopy revealed that TAC destroys the ultrastructure of cysts, both in vitro and in vivo. Furthermore, TAC had no significant effect on blood glucose, body weight, liver, or kidney functions in mice. We further observed that the ATP levels and glucose content of cysts reduced upon TAC treatment, indicating that inhibiting mTORC1 activity possibly affects glucose metabolism in the cysts of mice. Based on our experimental data, TAC emerged as a promising anti-cyst drug that efficiently inhibits the growth of cysts.