Integrative Multiomics and Regulatory Network Analyses Uncovers the Role of OAS3, TRAFD1, miR-222-3p, and miR-125b-5p in Hepatitis E Virus Infection.

The hepatitis E virus (HEV) is a long-ignored virus that has spread globally with time. It ranked 6th among the top risk-ranking viruses with high zoonotic spillover potential; thus, considering its viral threats is a pressing priority. The molecular pathophysiology of HEV infection or the underlying cause is limited. Therefore, we incorporated an unbiased, systematic methodology to get insights into the biological heterogeneity associated with the HEV. Our study fetched 93 and 2016 differentially expressed genes (DEGs) from chronic HEV (CHEV) infection in kidney-transplant patients, followed by hub module selection from a weighted gene co-expression network (WGCN). Most of the hub genes identified in this study were associated with interferon (IFN) signaling pathways. Amongst the genes induced by IFNs, the 2'-5'-oligoadenylate synthase 3 (OAS3) protein was upregulated. Protein-protein interaction (PPI) modular, functional enrichment, and feed-forward loop (FFL) analyses led to the identification of two key miRNAs, i.e., miR-222-3p and miR-125b-5p, which showed a strong association with the OAS3 gene and TRAF-type zinc finger domain containing 1 (TRAFD1) transcription factor (TF) based on essential centrality measures. Further experimental studies are required to substantiate the significance of these FFL-associated genes and miRNAs with their respective functions in CHEV. To our knowledge, it is the first time that miR-222-3p has been described as a reference miRNA for use in CHEV sample analyses. In conclusion, our study has enlightened a few budding targets of HEV, which might help us understand the cellular and molecular pathways dysregulated in HEV through various factors. Thus, providing a novel insight into its pathophysiology and progression dynamics.

Integrative multiomics and in silico analysis revealed the role of ARHGEF1 and its screened antagonist in mild and severe COVID-19 patients.

COVID-19 is a sneaking deadly disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid increase in the number of infected patients worldwide enhances the exigency for medicines. However, precise therapeutic drugs are not available for COVID-19; thus, exhaustive research is critically required to unscramble the pathogenic tools and probable therapeutic targets for the development of effective therapy. This study utilizes a chemogenomics strategy, including computational tools for the identification of viral-associated differentially expressed genes (DEGs), and molecular docking of potential chemical compounds available in antiviral, anticancer, and natural product-based libraries against these DEGs. We scrutinized the messenger RNA expression profile of SARS-CoV-2 patients, publicly available on the National Center for Biotechnology Information-Gene Expression Omnibus database, stratified them into different groups based on the severity of infection, superseded by identification of overlapping mild and severe infectious (MSI)-DEGs. The profoundly expressed MSI-DEGs were then subjected to trait-linked weighted co-expression network construction and hub module detection. The hub module MSI-DEGs were then exposed to enrichment (gene ontology + pathway) and protein-protein interaction network analyses where Rho guanine nucleotide exchange factor 1 (ARHGEF1) gene conjectured in all groups and could be a probable target of therapy. Finally, we used the molecular docking and molecular dynamics method to identify inherent hits against the ARHGEF1 gene from antiviral, anticancer, and natural product-based libraries. Although the study has an identified significant association of the ARHGEF1 gene in COVID19; and probable compounds targeting it, using in silico methods, these targets need to be validated by both in vitro and in vivo methods to effectively determine their therapeutic efficacy against the devastating virus.

Impact of COVID-19 pandemic on prevention and control of dengue in Delhi, India

The COVID-19 pandemic has impacted human lives worldwide and cases are still increasing at a fast pace in 2020. In India, the global challenge of COVID-19 started showing its impact during late March 2020. Delhi being a metropolitan city with an international air terminal, the corona virus disease initiated in Delhi due to in-migration of infected persons from various parts of the world. Key strategies adopted to control transmission of COVID-19 included: lockdown, surveillance of tourists staying in different hotels of Delhi, health education and capacity building programmes for travellers, hotels, children, nodal teachers, resident welfare associations, and different stake holder departments. The sharing of human resources, which were invested in activities related to COVID-19, posed challenges for prevention and control of vector-borne diseases (VBDs) in Delhi. Extensive vector surveillance and their control received a setback, but with administrative support by mobilizing human resources from other departments, the public health department was able to initiate control measures for VBDs. Social media and other electronic media are key strategies for community sensitization during such pandemics. Lockdown can have both positive and negative impacts in dengue transmission. The use of newer vector tools such as Gravid Trap/Ovitrap will help in vector surveillance when resources are limited for vector control. This article focuses on the efforts made to address the challenges for prevention and control of VBDs during the COVID-19 pandemic and the recommendations for such situations in future when resources are limited and shared.

Steroidal Saponins of Trillium govanianum: Quality Control, Pharmacokinetic Analysis, and Anti-inflammatoryActivity

Objective The rhizomes of Trillium govanianum have traditionally been used in the Ayurvedic system of medicine to treat inflammation, pain, burn, and reproductive malfunctions. However, the ethanopharmacology and chemical constituents of T. govanianum have not been effusively explored to date. The present study attempted to uncover the phytochemical constituents and quality parameters of T. govanianum rhizomes, along with an evaluation of the anti-inflammatory potential of the extract, fractions, and isolated steroidal saponins. Methods The quality of T. govanianum rhizomes was examined by standard guidelines of the Association of Official Agricultural Chemists (AOAC). The phytochemical composition of rhizomes was estimated by the spectroscopic method. The extract, fractions, and pure molecules were tested for their anti-inflammatory potential using lipopolysaccharide-stimulated RAW 264.7 macrophages. Besides that, computational pharmacokinetics properties of bioactive compounds were screened by using the Schrödinger software. Results The quality control parameters such as moisture content, ash value, pH, heavy metals, alpha toxins, residual pesticides, and microbial load were observed within the permitted limits as per AOAC guidelines, suggesting good quality and safe nature of T. govanianum rhizomes. Phytochemical analysis revealed the presence of steroidal saponins (78.3 ± 0.61 mg/g), phenolics (12.3 ± 2.76 mg/g), flavonoids (3.54 ± 0.24 mg/g), and carbohydrates (473 ± 2.27 mg/g) in the rhizomes. Macrophages cytocompatibility demonstrated that cell viability was not affected at any tested concentration of extract, fractions and pure compounds [diosgenin (1), borassoside D (2), and govanoside B (7)]. The LPS-stimulated macrophages secreted nitric oxide (NO) and pro-inflammatory cytokines (TNFα, IL-1β, and IL-6), which were inhibited by the extract, fractions, and compounds 1, 2, and 7 in a concentration-independent manner. Additionally, in silico pharmacokinetics revealed that compound 1 has good membrane-permeability followed by compound 2, while compound 7 showed the non-membrane permeability. Conclusion This study validates the traditional uses of rhizomes of T. govanianum in the treatment of inflammation, and this activity might be due to the presence of steroidal saponins.

Unravelling host-pathogen interactions: ceRNA network in SARS-CoV-2 infection (COVID-19).

COVID-19 is a lurking calamitous disease caused by an unusual virus, SARS-CoV-2, causing massive deaths worldwide. Nonetheless, explicit therapeutic drugs or clinically approved vaccines are not available for COVID-19. Thus, a comprehensive research is crucially needed to decode the pathogenic tools, plausible drug targets, committed to the development of efficient therapy. Host-pathogen interactions via host cellular components is an emerging field of research in this respect. miRNAs have been established as vital players in host-virus interactions. Moreover, viruses have the capability to manoeuvre the host miRNA networks according to their own obligations. Besides protein coding mRNAs, noncoding RNAs might also be targeted in infected cells and viruses can exploit the host miRNA network via ceRNA effect. We have predicted a ceRNA network involving one miRNA (miR-124-3p), one mRNA (Ddx58), one lncRNA (Gm26917) and two circRNAs (Ppp1r10, C330019G07RiK) in SARS-CoV infected cells. We have identified 4 DEGs-Isg15, Ddx58, Oasl1, Usp18 by analyzing a mRNA GEO dataset. There is no notable induction of IFNs and IFN-induced ACE2, significant receptor responsible for S-protein binding mediated viral entry. Pathway enrichment and GO analysis conceded the enrichment of pathways associated with interferon signalling and antiviral-mechanism by IFN-stimulated genes. Further, we have identified 3 noncoding RNAs, playing as potential ceRNAs to the genes associated with immune mechanisms. This integrative analysis has identified noncoding RNAs and their plausible targets, which could effectively enhance the understanding of molecular mechanisms associated with viral infection. However, validation of these targets is further corroborated to determine their therapeutic efficacy.