Kazi Faizul Azim

White spot syndrome virus (WSSV) is one of the most devastating shrimp pathogens that causes a potential loss in penaeid shrimp farming. White spot syndrome (WSS) was considered as epizootic in the major shrimp farming nations and currently, no approved medications are available to prevent the infection. Owing to the scientific progress made in the recent decades, it has been possible to identify the genomic mutations and variations of WSSV of distinctive geographic regions. Due to the scarcity of appropriate therapeutics against WSSV, it is crucial to mitigate the risk of infection through early detection of the virus by exploiting suitable diagnostic tools. Also, while ample diagnostic approaches are in use, literature with detailed and updated information is quite limited. The genomic variations in specific loci of WSSV discussed in this review would help in understanding the genomic evolution respective to several lineages of the virus.

The deeper understanding of metastasis phenomenon and detection of drug targets could be a potential approach to minimize cancer mortality. In this study, attempts were taken to unmask novel therapeutics to prevent metastasis and cancer progression. Initially, we explored the physiochemical, structural and functional insights of three metastasis tumor antigens (MTAs) and evaluated some plant-based bioactive compounds as potent MTA inhibitors. From 50 plant metabolites screened, isoflavone, gingerol, citronellal and asiatic acid showed maximum binding affinity with all three MTA proteins. The ADME analysis detected no undesirable toxicity that could reduce the drug likeness properties of top plant metabolites. Moreover, molecular dynamics studies revealed that the complexes were stable and showed minimum fluctuation at molecular level. We further performed ligand-based virtual screening to identify similar drug molecules using a large collection of 376,342 compounds from DrugBank. The results suggested that several structural analogs (e.g., tramadol, nabumetone, DGLA and hydrocortisone) may act as agonist to block the MTA proteins and inhibit cancer progression at early stage. The study could be useful to develop effective medications against cancer metastasis in future. Due to encouraging results, we highly recommend further in vitro and in vivo trials for the experimental validation of the findings. Graphic abstract

The high infectivity and mortality of novel coronavirus has caused a serious concern all over the world. Still, there is no specific drug or preventive medication to treat SARS-CoV-2 infection despite comprehensive analysis by the researchers. This study was designed to demonstrate the efficacy of some phyto-chemical compounds against SARS-CoV-2 by using both structure and ligand based virtual screening methods. A total of 33 plant metabolites were screened against SARS-CoV-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding domain and HR2 domain using a molecular docking approach. Results showed that three metabolites, i.e., Limonin, Isoflavone, and Coumadin conferred maximum binding affinity with all key proteins of SARS-CoV-2. For each viral protein, the critical binding sites and drug surface hotspots have been unraveled. ADME analysis indicated that none of the compounds have adverse effects that could decrease their drug-like properties. Moreover, toxicity pattern analysis also unmasked the non-toxic nature of the top drug candidates. The RMSD values of top ligandmacromolecule complexes were less than 2 Å, while RMSF values showed regular atomic fluctuations in the molecular dynamics study. Notably, most of the target class by top drug candidates belonged to enzyme groups (e.g. oxidoreductases, protease, Kinase). Results of drug similarity prediction revealed two approved structural analogs of Coumadin named Warfarin (DB00682) and Phenprocoumon (DB00946) from DrugBank. In addition, Isoformononetin an experimental drug analog of isoflavone could also be an option for the treatment of viral infections. For limonin there was no analog found in drugbank. The study can pave the way for the creation of effective SARS-CoV-2 medications and preventive measures. We highly recommend further in vivo trials for the experimental validation of our findings

The deeper understanding of metastasis phenomenon and detection of drug targets could be a potential approach to minimize cancer mortality. In this study, attempts were taken to unmask novel therapeutics to prevent metastasis and cancer progression. Initially, we explored the physiochemical, structural and functional insights of three metastasis tumor antigens (MTAs) and evaluated some plant based bioactive compounds as potent MTA inhibitors. From 50 plant metabolites screened, isoflavone, gingerol, citronellal and asiatic acid showed maximum binding affinity with all three MTA proteins. The ADME analysis detected no undesirable toxicity that could reduce the drug likeness properties of top plant metabolites. Moreover, molecular dynamics studies revealed that the complexes were stable and showed minimum fluctuation at molecular level. We further performed ligand based virtual screening to identify similar drug molecules using a large collection of 3,76,342 compounds from DrugBank. The results suggested that several structural analogs (e.g. Tramadol, Nabumetone, DGLA, Hydrocortisone) may act as agonist to block the MTA proteins and inhibit cancer progression at early stage. The study could be useful to develop effective medications against cancer metastasis in future. Due to encouraging results, we highly recommend further in vitro and in vivo trials for the experimental validation of the findings.

Multidrug-resistant Vibrio parahaemolyticus has become a significant public health concern. The development of effective drugs and vaccines against Vibrio parahaemolyticus is the current research priority. Thus, we aimed to find out effective drug and vaccine targets using a comprehensive genome-based analysis. A total of 4822 proteins were screened from V. parahaemolyticus proteome. Among 16 novel cytoplasmic proteins, ‘VIBPA Type II secretion system protein L’ and ‘VIBPA Putative fimbrial protein Z’ were subjected to molecular docking with 350 human metabolites, which revealed that Eliglustat, Simvastatin and Hydroxocobalamin were the top drug molecules considering free binding energy. On the contrary, ‘Sensor histidine protein kinase UhpB’ and ‘Flagellar hook-associated protein of 25 novel membrane proteins were subjected to T-cell and B-cell epitope prediction, antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking analysis to generate the most immunogenic epitopes. Three subunit vaccines were constructed by the combination of highly antigenic epitopes along with suitable adjuvant, PADRE sequence and linkers. The designed vaccine constructs (V1, V2, V3) were analyzed by their physiochemical properties and molecular docking with MHC molecules- results suggested that the V1 is superior. Besides, the binding affinity of human TLR-1/2 heterodimer and construct V1 could be biologically significant in the development of the vaccine repertoire. The vaccine-receptor complex exhibited deformability at a minimum level that also strengthened our prediction. The optimized codons of the designed construct was cloned into pET28a(+) vector of E. coli strain K12. However, the predicted drug molecules and vaccine constructs could be further studied using model animals to combat V. parahaemolyticus associated infections.

The sudden outbreak of novel corona virus at the end of 2019 has caused a global threat to mankind due to its extreme infection rate and mortality. Despite extensive research, still there is no an approved drug or vaccine to combat SARS-CoV-2 infections. Hence, the study was designed to evaluate some plant-based active compounds for drug candidacy against SARS-CoV-2 by using virtual screening methods and various computational analysis. A total of 27 plant metabolites were screened against SARS-Cov-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding domain, spike ecto-domain and HR2 domain using molecular docking approach. Four metabolites i.e. asiatic acid, avicularin, guajaverin and withaferin showed maximum binding affinity with all key proteins in terms of lowest global binding energy. The top candidates were further employed for ADME (absorption, distribution, metabolism, and excretion) analysis to investigate their drug profiles. Results suggest that none of the compounds render any undesirable consequences that could reduce their drug likeness properties. The analysis of toxicity pattern revealed no significant tumorigenic, mutagenic, irritating or reproductive effects by the compounds. However, witheferin was comparatively toxic among the top four candidates with considerable cytotoxicity and immunotoxicity. Most of the target class by top drug candidates belonged to enzyme groups (e.g. oxidoreductases hydrolases, phosphatases). Moreover, results of drug similarity prediction identified two approved structural analogs of Asiatic acid from DrugBank, Hydrocortisone (DB00741) (previously used for SARS-CoV-1 and MERS) and Dinoprost-tromethamine (DB01160). In addition, two other biologically active compounds, Mupirocin (DB00410) and Simvastatin (DB00641) could be an alternative choice to witheferin for the treatment of viral infections. The study may pave the way to develop effective medications and preventive measure against SARS-CoV-2 in the future. However, the results were based solely on computational tools and algorithms. Due to the encouraging results, we highly recommend further in vivo trials for the experimental validation of our findings.

Corchorus capsularis, commonly known as jute occupies the leading position in the production of natural fibre and fibre based products alongside lower environmental threat. Nowadays, the study of lignin biosynthesis pathways with other molecular basis of fibres formation are being more focused for its economic perspective. Small noncoding ∼21 to 24 nt nucleotides long microRNAs play significant roles in regulating the gene expression as well as different functions in cellular growth and development. Here, the study adopted a comprehensive in silico approach to identify and characterize the conserved miRNAs in the genome of C. capsularis including specific gene targets involved in the crucial cellular process. Expressed Sequence Tags (ESTs) based homology search of 3350 known miRNAs of dicotyledons were allowed against 763 non-redundant ESTs of jute genome resulted in the prediction of 5 potential miRNA candidates belonging five different miRNA families (miR1536, miR9567-3p, miR4391, miR11300, and miR8689). The putative miRNAs were 18 nucleotide length, within a range of -0.49 to -1.56 MFEI values and 55% to 61% of (A+U) content of their correspondence pre-miRNAs. A total of 1052 gene targets of putative miRNAs were identified and their functions were extensively analyzed. Most of the gene targets were involved in plant growth, cell cycle regulation, organelle synthesis, developmental process and environmental responses. The five gene targets, namely, NAC Domain Containing Protein, WRKY DNA binding protein, 3-dehydroquinate synthase, S-adenosyl-L-Met–dependent methyl transferase and Vascular-related NAC-Domain were found to be involved in the lignin biosynthesis, phenylpropanoid pathways and secondary wall formation which could play significant roles in the overall fibre biogenesis. The characterization of conserved miRNAs and their functional annotation of specific gene targets might enhance the more miRNA discovery, strengthening the complete understanding of miRNAs association in the cellular basis of lignin biosynthesis towards the production of high standard jute products.

Multidrug-resistant Vibrio parahaemolyticus has become a significant threat to human health as well as aquaculture, prioritizing the development of effective drug and vaccine candidates. Hence, the study was designed to identify novel therapeutics using a comprehensive genome-based analysis of V. parahaemolyticus. From V. parahaemolyticus proteome, a total of 4822 proteins were investigated in order to find out effective drug and vaccine targets. A range of diverse subtractive proteomics approaches – namely, identification of human non-homologous and pathogen-specific essential proteins, druggability and ‘anti-target’ analysis, prediction of subcellular localization, human microbiome non-homology screening, analysis of virulence factors, protein-protein interactions studies. Among 16 novel cytoplasmic proteins, ‘VIBPA Type II secretion system protein L’ and ‘VIBPA Putative fimbrial protein Z’ were allowed to molecular docking with 350 human metabolites, which revealed that Eliglustat, Simvastatin and Hydroxocobalamin were the top drug molecules considering free binding energy. On the contrary, ‘Sensor histidine protein kinase UhpB’ and ‘Flagellar hook-associated protein of 25 novel membrane proteins were subjected to T and B cell epitope prediction, antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking were adopted to generate the most immunogenic epitopes. Three subunit vaccines were constructed by the combination of highly antigenic epitopes along with suitable adjuvant, PADRE sequence and linkers. The designed vaccine constructs (V1, V2, V3) were analyzed by their physiochemical properties and molecular docking with MHC molecules that suggested the superiority of construct V1. Besides, the binding affinity of human TLR1/2 heterodimer and construct V1 was also biologically significant. The vaccine-receptor complex exhibited deformability at a minimum level that also strengthened our prediction. The optimized codons of the designed construct was cloned into pET28a(+) vector of E. coli strain K12. However, the predicted drug molecules and vaccine constructs could be further studied to combat V. parahaemolyticus associated infections.