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The coronavirus disease 2019 (COVID-19), which emerged in December 2019, continues to be a serious health concern worldwide. There is an urgent need to develop effective drugs and vaccines to control the spread of this disease. In the current study, the main phytochemical compounds of Nigella sativa were screened for their binding affinity for the active site of the RNA-dependent RNA polymerase (RdRp) enzyme of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The binding affinity was investigated using molecular docking methods, and the interaction of phytochemicals with the RdRp active site was analyzed and visualized using suitable software. Out of the nine phytochemicals of N. sativa screened in this study, a significant docking score was observed for four compounds, namely α-hederin, dithymoquinone, nigellicine, and nigellidine. Based on the findings of our study, we report that α-hederin, which was found to possess the lowest binding energy (-8.6 kcal/mol) and hence the best binding affinity, is the best inhibitor of RdRp of SARS-CoV-2, among all the compounds screened here. Our results prove that the top four potential phytochemical molecules of N. sativa, especially α-hederin, could be considered for ongoing drug development strategies against SARS-CoV-2. However, further in vitro and in vivo testing are required to confirm the findings of this study.

Background: Dengue virus is a potential source of propagating dengue hemorrhagic fever. This virus leads to dengue hemorrhagic fever/dengue shock syndrome, benign syndrome, and severe syndrome and due to its infection, there occurs alterations at multiple levels such as gene expression and pathway levels. So, it is critical to understand the pathogenesis of dengue infection in terms of gene expression and the associated functions. Methods: For this purpose, here, we have analyzed the temporal gene expression profiling for the dengue hemorrhagic fever dataset at 12, 24, and 48 hours. Results: The outcome appears that the dengue hemorrhagic fever evolves differently at different time periods or stages. Counclusions: The change in the gene expression pattern increases exponentially from 12 hours to 48 hours and the number of altered functions (pathways) also increases. Wnt, apoptosis, and transcription signaling are among the critical pathways which are dominantly altered. In the initial phase (first 12 hours), only two pathways are altered due to dengue infection, while in the next 12 hours, eight pathways are altered, and finally, in the next 24 hours, 11 pathways are altered and most of these 11 pathways are very critical in terms of biological pathways and functions.

Cadmium (Cd) is a toxic heavy metal and an abiotic stressor to plants; however, inoculation of endophytic bacteria can raise resistance in plants against Cd, as well as improve plant growth. In the present study, two endophytic bacterial strains were isolated from Solanum nigrum, identified as Serratia sp. IU01 and Enterobacter sp. IU02 by 16S DNA sequencing. Both IU01 and IU02 were tolerant up to 9.0 mM of Cd in culture broth and successive increase in Cd concentration from 0 mM to 9.0 mM, led to an increase in the SOD enzyme activity of the isolates. Both strains were capable of indole-3-acetic acid (IAA) synthesis and phosphate solubilization, detected through gas spectrometry-mass chromatography (GC-MS) and Pikovskaya agar medium respectively. Brassica juncea plants stressed with 0–25 mg/kg Cd showed retardation in all growth attributes, however, inoculation of strain IU01 and IU02 significantly promoted the plant growth attributes as compared to control. Moreover, antioxidant enzymes and metabolites against reactive oxygen species (ROS) including polyphenol oxidase (PPO), peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), alcohol dehydrogenase (ADH), reduced glutathione (GSH), malondialdehyde (MDA), flavonoid and polyphenolic contents were also significantly relieved by inoculation of IU01 and IU02 in plant exposed to different concentration of Cd stress as compared to control plants. Phytohormone production, phosphate solubilization, and/or antioxidative support of IU01 and IU02 might be responsible for growth promotion and Cd resistance in the plant.

Marine species are known as rich sources of metabolites involved mainly in the pharmaceutical industry. This study aimed to evaluate the effect of biologically active compounds in the marine sponge on the SARS-CoV-2 RNA-dependent-RNA polymerase protein (RdRp) using the in-silico method. A total of 51 marine compounds were checked for their possible interaction with SARS-CoV-2 RdRp using Maestro interface for molecular docking, molecular dynamic (MD) simulation, and MM/GBSA method to estimate compounds binding affinities. Among the 51 compounds screened in this study, two (mycalamide A, and nakinadine B) exhibited the lowest docking energy and best interaction. Among these compounds, mycalamide A was identified as a potent inhibitor of SARS-CoV-2 RdRp that showed the best and stable interaction during molecular dynamic simulation, with residues (Asp760 and Asp761) found in the catalytic domain of RdRp. The analysis through MM/GBSA for molecular dynamic simulation results revealed binding energy −59.7 ± 7.18 for Mycalamide A and −56 ± 10.55 for Nakinadine B. These results elucidate the possible use of mycalamide A for treating coronavirus disease. Communicated by Ramaswamy H. Sarma

The facile bio-fabrication of zinc oxide (ZnO) nanoparticles (NPs) is described in this study using an aqueous leaf extract of Salvia officinalis&nbsp, L. as an efficient stabilizing/capping agent. Biosynthesis of nanomaterials using phytochemicals present in the plants has received great attention and is gaining significant importance as a possible alternative to the conventional chemical methods. The properties of the bio-fabricated ZnONPs were examined by different techniques, such as UV-visible spectroscopy, X-ray diffraction spectroscopy (XRD), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and thermogravimetric/differential scanning calorimetry analysis (TGA/DTG). The photocatalytic activity of ZnONPs was investigated against methyl orange (MO) under UV light irradiation. Under optimum experimental conditions, ZnONPs exhibited 92.47% degradation of MO. Furthermore, the antifungal activity of bio-fabricated ZnONPs was determined against different clinical Candida albicans isolates following standard protocols of broth microdilution and disc diffusion assay. The susceptibility assay revealed that ZnONPs inhibit the growth of all the tested fungal isolates at varying levels with MIC values ranging from 7.81 to 1.95 µg/mL. Insight mechanisms of antifungal action appeared to be originated via inhibition of ergosterol biosynthesis and the disruption of membrane integrity. Thus, it was postulated that bio-fabricated ZnONPs have sustainable applications in developing novel antifungal agents with multiple drug targets. In addition, ZnONPs show efficient photocatalytic efficiency without any significant catalytic loss after the catalyst was recycled and reused multiple times.

Glycogenes regulate a large number of biological processes such as cancer and development. In this work, we created an interaction network of 923 glycogenes to detect potential hubs from different mouse tissues using RNA-Seq data. DAVID functional cluster analysis revealed enrichment of immune response, glycoprotein and cholesterol metabolic processes. We also explored nsSNPs that may modify the expression and function of identified hubs using computational methods. We observe that the number of nsSNPs predicted by any two methods to affect protein function is 4, 7 and 2 for FLT1, NID2 and TNFRSF1B. Residues in the native and mutant proteins were analyzed for solvent accessibility and secondary structure change. Analysis of hubs can help in determining their degree of conservation and understanding their functions in biological processes. The nsSNPs proposed in this work may be further targeted through experimental methods for understanding structural and functional relationships of hub mutants.

Ovarian cancer is a leading cause of death due to the fact that most of the patients are diagnosed at an advanced stage(s) of disease progression because it cannot be detected at the early stage. An immunogenic tumor and immunotherapy is strongly pursued through targeting the immune checkpoints. In previous study, the immune signaling pathways and their components have been shown as a key factor for cancer initiation, progression, and finally a scope for diagnosis. Thus, in ovarian cancer the immune-based prognostic signature remains a potential that can be explored further. We have used gene expression GEO dataset with the focus to understand how the signaling pathways and their components altered are relevant to the immune system related functions. Finally, we have explored the possible herbal drug targets (Apigenin, Quercetin, and Resveratrol) based on gene expression profiling. The herbal drug structures have been retrieved from PubChem database and the 3D protein structures for the top-ranked genes have been obtained by using SwissModel tool and in the next step SwissDock tool has been applied for performing docking studies of the herbal drugs against the top ranked differentially expressed genes. We concluded that for ovarian cancer, immune systems associated pathways are TCR, UPS, Foxo, neuroactive ligand-receptor interaction, adrenergic, NK cell, TGF, TNF, NF-kB, BCR, and APC and docking profiling reveals that the most likely targets for quercetin are GNAI3, FGFR1, and LGALS3 while apigenin and resveratrol follow the similar trends in terms of delta G. Network-based study of the docked proteins reveals that FGFR1, GNAI3, RAC1, and RHEB control a large number of DEGs of immune system and the cluster of these genes also connect each other.

The West Nile virus (WNV) infections are generally asymptomatic and are considered as immediate concerns of biodefense due to the lack of any therapeutic remedies. In this work, we created an interaction network of 1159 differentially expressed genes to detect potential hub genes from WNV infected primary human macrophages. We go on to explore the genetic variations that can alter the expression and function of identified hub genes (HCLS1, SLC15A3, HCK, and LY96) using the PROVEAN Protein Batch tool and PolyPhen-2. Community analysis of the network revealed that these clusters were enriched in GO terms such as inflammatory response and regulation of proliferation. Analysis of hub genes can aid in determining their degree of conservation and may help us in understanding their functional roles in biological systems. The nsSNPs proposed in this work may be further targeted through experimental methods for improving treatment towards the infection of WNV.

Plasmodium falciparum, the deadly protozoan parasite, causes malaria. Malaria remains one of the deadliest infectious diseases in the world. The RNA-Seq data sets were downloaded from NCBI Short Read Archive under accession number SRP009370 for our analysis. Differentially expressed genes (DEGs) between Ring (R) and early trophozoite (ET), late trophozoite (LT), schizont (Sc), gametocyte stages (GII), gametocyte stages (GV), ookinete (Oo) stages are 2442, 2796, 2935, 2807, 2180, 2895 respectively. There are total 4594 unique DEGs in the samples. DAVID was used to categorize enriched biological themes in the list of DEGs. It can be seen that main functions related to GO term ‘Biological Process’ are antigenic variation, pathogenesis, single organismal cell-cell adhesion, GO term ‘Cellular Component’ are host cell plasma membrane, infected host cell surface knob and GO term ‘Molecular Function’ are cell adhesion molecule binding, ATP-dependent RNA helicase activity. We found that PF3D7_1000400, PF3D7_1000600, PF3D7_0900500, PF3D7_0901500, PF3D7_0937400 were most up regulated and PF3D7_0632800, PF3D7_0711700, PF3D7_0712400, PF3D7_0712600, PF3D7_0712900, PF3D7_0808600 and PF3D7_0808700 were most down regulated genes involved in antigenic variation. Also PF3D7_0930300 was most up-regulated in Sc, LT and Oo stages and PF3D7_0936500 was most up-regulated in GV stage and PF3D7_0632800, PF3D7_0711700, PF3D7_0712400, PF3D7_0712600, PF3D7_0712900, PF3D7_0808600, PF3D7_0808700 were most down regulated genes involved in pathogenesis. A total of 300 pathways were predicted using KAAS server. Majority of the DEGs were found to be associated with important biological pathways such as metabolic pathways, biosynthesis of secondary metabolites, ribosome, spliceosome, biosynthesis of antibiotics, purine metabolism.

The information necessary for proteins to correctly fold into biologically active three dimensional (3D) structures is present in the amino acid sequence. The ways by which proteins fold still remain one of the unexplained mysteries in the field of protein biochemistry. Investigating the impact and consequences of protein misfolding can help decipher the molecular causes behind the complex amyloid diseases such as Alzheimer’s disease (AD) and Parkinson’s disease. Various participating molecular entities like amyloid beta (Aβ), tau protein, and non-beta sheets are facilitating the pathogenesis of Alzheimer’s disease. Understanding their structure as well as their mechanism of action is useful to decode the therapeutic treatment for these complex diseases.

Glycogenes regulate a wide array of biological processes in the development of organisms as well as different diseases such as cancer, primary open-angle glaucoma, and renal dysfunction. The objective of this study was to explore the role of differentially expressed glycogenes (DEGGs) in three major tissues such as brain, muscle, and liver using mouse RNA-seq data, and we identified 579, 501, and 442 DEGGs for brain versus liver (BvL579), brain versus muscle (BvM501), and liver versus muscle (LvM442) groups. DAVID functional analysis suggested inflammatory response, glycosaminoglycan metabolic process, and protein maturation as the enriched biological processes in BvL579, BvM501, and LvM442, respectively. These DEGGs were then used to construct three interaction networks by using GeneMANIA, from which we detected potential hub genes such asPEMTandHPXN(BvL579),IGF2andNID2(BvM501), andSTAT6andFLT1(LvM442), having the highest degree. Additionally, our community analysis results suggest that the significance of immune system related processes in liver, glycosphingolipid metabolic processes in the development of brain, and the processes such as cell proliferation, adhesion, and growth are important for muscle development. Further studies are required to confirm the role of predicted hub genes as well as the significance of biological processes.

Background Adenine and guanine phosphates are involved in a number of biological processes such as cell signaling, metabolism and enzymatic cofactor functions. Binding sites in proteins for these ligands are often detected by looking for a previously known motif by alignment based search. This is likely to miss those where a similar binding site has not been previously characterized and when the binding sites do not follow the rule described by predefined motif. Also, it is intriguing how proteins select between adenine and guanine derivative with high specificity. Results Residue preferences for AMP, GMP, ADP, GDP, ATP and GTP have been investigated in details with additional comparison with cyclic variants cAMP and cGMP. We also attempt to predict residues interacting with these nucleotides using information derived from local sequence and evolutionary profiles. Results indicate that subtle differences exist between single residue preferences for specific nucleotides and taking neighbor environment and evolutionary context into account, successful models of their binding site prediction can be developed. Conclusion In this work, we explore how single amino acid propensities for these nucleotides play a role in the affinity and specificity of this set of nucleotides. This is expected to be helpful in identifying novel binding sites for adenine and guanine phosphates, especially when a known binding motif is not detectable.

Rubber trees infected with a host-specific cassiicolin toxin often experience considerable leaf fall, which in turn results in loss of crop productivity. It was recently revealed that cassiicolin-specific single-chain variable fragments (scFv) can successfully reduce the toxic effects of cassiicolin. However, the detailed mechanism of antibody action remains poorly understood. The primary sequence of the newly sequenced cassiicolin-specific scFv was highly homologous to several members of single-chain antibodies in the 14B7 family. In this study, with the aid of homology modeling, the three-dimensional structure of cassiicolin-specific scFv was elucidated, and was found to exhibit a characteristic immunoglobulin fold that mainly consists of β sheets. Additionally, molecular docking between the modeled scFv antibody and the available three-dimensional crystal structure of cassiicolin toxin was also performed. The predicted structural complex and the change in accessible surface area between the toxin and the scFv antibody upon complexation reveal the potential role of certain complementarity determining region (CDR) amino acid residues in the formation of the complex. These computational results suggest that mutagenesis experiments that are aimed at validating the model and improving the binding affinity of cassiicolin-specific scFv antibodies for the toxin should be performed.

In the present study, we have evaluated prophylactic role of various immunomodulators viz. lipopolysachharide, protein A and tuftsin to impart protection against experimental candidiasis in leukopenic mice. Both free as well as liposomised form of nystatin was not effective enough in offering complete cure against less susceptible isolate of Candida albicans (JNMCR) infection in immunodebilitant mice. Interestingly, the pretreatment of leukopenic mice with immunomodulators before challenging them with C. albicans increased therapeutic efficacy of the nystatin against systemic candidiasis. Efficacy of the treatment was evaluated on the basis of survival of the animals as well as fungal load in systemic circulation and various organs viz. liver, kidney, spleen and lungs of the treated animals.

In order to develop a prospective chemotherapeutic agent against opportunistic infections, it is important to know that host factors such as degree of immunological debility as well as recovery of immune functions to normality may contribute significantly to a successful elimination of the pathogens. We demonstrated previously that concomitant delivery of antimicrobial agents and immunomodulators to the pathogen harbouring-host contributes to the complete elimination of the deep-seated fungal infections (aspergillosis and candidiasis) in animals with normal immune status. Considering that neutropenic hosts are the main targets of such infections, it can be argued about the potential of the immunomodulator-based therapy in subjects with non-functional immune system. To resolve the hypothesis, we studied the role of immunomodulator tuftsin against experimental murine candidiasis in temporarily neutropenic Balb/c mice. The neutropenic mice were challenged with an isolate of Candida albicans that was showing less susceptibility to both free and liposomised-amphotericin B. The co-administration of tuftsin increased the efficiency of liposomised-polyene antibiotics (nystatin and amphotericin B) against experimental murine candidiasis in immunocompromised Balb/c mice. Pretreatment with liposomised tuftsin prior to C. albicans infection clearly enhanced protection against candidiasis, suggesting a prophylactic role of tuftsin in normal and temporarily neutropenic animals.