Identification of the Seaweed Metabolites as Potential Anti-tubercular Agents Against Human Pantothenate synthetase: An In Silico Approach.

Tuberculosis is the disease which is caused due to the contagion of Mycobacterium tuberculosis. The multidrug resistance Mycobacterium tuberculosis is the main hassle in the treatment of this worldwide health threats. Pantothenate synthase is a legitimate goal for rational drug designing against Mycobacterium tuberculosis. The enzyme is most active in the presence of magnesium or manganese. Marine algal cell wall is rich in sulfated polysaccharides such as fucoidans (brown algae), κ-carrageenans (red algae), and ulvan (green algae) with various favorable biological activities such as anticoagulant, antiviral, antioxidative, anticancer, and immunomodulating activities. In this study, we have modeled binding modes of selected known anti-tubercular compounds and different solvent extract against pantothenate synthase using advanced docking program AutoDock 4.2 tool. In our current study, in silico experiments were carried out to determine if fucoidan, κ-carrageenan, and ulvan sulfated polysaccharides could be a potential target against PANc (pantothenate synthetase), with the goal of identifying potential inhibitors as anti-TB leads targeting PANc for further wet lab validation. Two bioactive compounds were docked to the Mtb pantothenate synthetase protein binding site, with docking scores ranging from - 5.57 to - 2.73. κ-carrageenan had the best pose and docking score, with a Ligand fit score of - 5.815. Ulvan did not dock with the protein. The molecular dynamics simulations were conducted with substrate and ligand bounded fucoidan and κ-carrageenan for 150 ns and the protein Mtb pantothenate synthetase showed a stable conformation in the simulation, with tight amino acid contributions binding to the ligand molecule. RMSD characterizes the conformation and stability of protein ligand complexes, with higher fluctuations indicating low stability and minimal low-level fluctuations indicating equilibration and stability. The graph for RMSF shows significant peaks due to fluctuations in active site regions and other peaks indicating the adaptation of the ligand molecule to the protein binding pocket. From the molecular dynamics study, it is clear that the compounds are having good binding affinity in the active site. The root mean square deviation, root mean square fluctuations, and radius of gyration are supportive evidences which helped us to conclude that the compounds κ-carrageenan and fucoidan are suitable lead molecules for inhibiting pantothenate synthetase. Based on these evidences, the natural compounds from seaweeds can be tested clinically either alone or in combinations against the protein, which could facilitate the designing or the synthesis of new lead molecules as drugs against the tuberculosis.

A Novel Finding: 2,4-Di-tert-butylphenol from Streptomyces bacillaris ANS2 Effective Against Mycobacterium tuberculosis and Cancer Cell Lines.

The aim of the present study is to identify actinobacteria Streptomyces bacillaris ANS2 as the source of the potentially beneficial compound 2,4-di-tert-butylphenol, describe its chemical components, and assess its anti-tubercular (TB) and anti-cancer properties. Ethyl acetate was used in the agar surface fermentation of S. bacillaris ANS2 to produce the bioactive metabolites. Using various chromatographic and spectroscopy analyses, the potential bioactive metabolite separated and identified as 2,4-di-tert-butylphenol (2,4-DTBP). The lead compound 2,4-DTBP inhibited 78% and 74% of relative light unit (RLU) decrease against MDR Mycobacterium tuberculosis at 100ug/ml and 50ug/ml concentrations, respectively. The Wayne model was used to assess the latent/dormant potential in M. tuberculosis H37RV at various doses, and the MIC for the isolated molecule was found to be 100ug/ml. Furthermore, the molecular docking of 2,4-DTBP was docked using Autodock Vinasuite onto the substrate binding site of the target Mycobacterium lysine aminotransferase (LAT) and the grid box was configured for the docking run to cover the whole LAT dimer interface. At a dosage of 1 mg/ml, the anti-cancer activity of the compound 2,4-DTBP was 88% and 89% inhibited against the HT 29 (colon cancer) and HeLa (cervical cancer) cell lines. According to our literature survey, this present finding may be the first report on anti-TB activity of 2,4-DTBP and has the potential to become an effective natural source and the promising pharmaceutical drug in the future.

Actinobacteria as a source of biofertilizer/biocontrol agents for bio-organic agriculture.

The global human population keeps growing and natural energy supplies are depleting, creating a threat to environmental demands, food security, and energy supply. As a result, increased agricultural output is required to accomplish the rising population's food demands. A strong reliance on chemical fertilizers to boost food production has harmed the environment and human health, and it is becoming too expensive as well. One of the potential solution to this problem is to use beneficial microorganisms as a substitute for artificial fertilizers in food production. Actinobacteria have been used as the most successful and long-lasting microorganisms throughout evolution. They are thought to be one of the most primordial living forms on our planet. Actinobacteria, particularly Streptomyces, have proved their ability to formulate biofertilizers in the agricultural sector by supplying nutrients to plants for better growth, increasing yield, managing abiotic and biotic stress, and resisting phytopathogen assault. This review describes the mechanism of actinobacterial biofertilizers used in the current agricultural market and their challenges and future importance to sustainable agriculture.

Biocontrol Streptomyces Induces Resistance to Bacterial Wilt by Increasing Defense-Related Enzyme Activity in Solanum melongena L.

Streptomyces strains were isolated from rhizosphere soil and evaluated for in vitro plant growth and antagonistic potential against Ralstonia solanacearum. Based on their in vitro screening, seven Streptomyces were evaluated for plant growth promotion (PGP) and biocontrol efficacy by in-planta and pot culture study. In the in-planta study, Streptomyces-treated eggplant seeds showed better germination percentage, plant growth, and disease occurrence against R. solanacearum than the control treatment. Hence, all seven Streptomyces cultures were developed as a bioformulation by farmyard manure and used for pot culture study. The highest plant growth, weight, and total chlorophyll content were observed in UP1A-1-treated eggplant followed by UP1A-4, UT4A-49, and UT6A-57. Similarly, the maximum biocontrol efficacy was observed in UP1A-1-treated eggplants against bacterial wilt. The biocontrol potential of Streptomyces is also confirmed through metabolic responses by assessing the activities of the defense-related enzymes peroxidase (POX), polyphenol oxidase (PPO), and phenylalanine ammonia-lyase (PAL) and as well as the levels of total phenol. Treatment with UP1A-1/ UT4A-49 and challenge with R. solanacearum led to maximum changes in the activities of POX, PPO, and PAL and the levels of total phenol in the eggplants at different time intervals. Alterations in enzymes of UP1A-1 treatment were related to early defense responses in eggplant. Therefore, the treatment with UP1A-1 significantly delayed the establishment of bacterial wilt in eggplant. Altogether, the present study suggested that the treatment of Streptomyces maritimus UP1A-1 fortified farmyard manure has improved the plant growth and stronger disease control against R. solanacearum on eggplant.

Anti-Biofilm Activity and Biocontrol Potential of Streptomyces Cultures Against Ralstonia solanacearum on Tomato Plants.

Biological control of phytopathogen is a promising approach when compared to the use of chemical agents. In the present study, seven Streptomyces cultures showing promising anti biofilm activity against Ralstonia solanacearum was mixed individually with farmyard manure. All the Streptomyces fortified farmyard manure (SFYM) were screened for plant growth promotion and control of bacterial wilt caused by R. solanacearum on tomato. Further, the ability of SFYM on stimulating the production of defense-related enzymes in R. solanacearum-inoculated tomato plants was investigated. When compared to the control tomato plants, the SFYM-treated plants had longer shoot and root length along with higher fresh and dry weight. The maximum level of chlorophyll was observed in the plants treated with strain UP1A-1 (2.21 ± 0.18 mg g-1). Strain UP1A-1 also showed maximum of 96.8 ± 1.4% biocontrol efficacy in tomato plants challenged with R. solanacearum. In addition, the UP1A-1 treated tomato plants showed maximum accumulation of total phenolics (3.02 ± 0.09 mg g-1) after 6 days of pathogen inoculation (DPI). Similarly, tomato plants treated with UP1A-1 showed highest level of peroxides, polyphenol oxidase and phenylalanine ammonia lyase during 1-9 DPI. Findings of present study revealed that the Streptomyces culture UP1A-1 fortified farm yard manure could be applied as an eco-friendly alternative to synthetic agents for controlling bacterial wilt in tomato plants.

Advance research in biomedical applications on marine sulfated polysaccharide.

Marine ecosystem associated organisms are an affluent source of bioactive compounds. Polysaccharides with unique structural and practical entities have gained special studies interest inside the current biomedical zone. Polysaccharides are the main components of marine algae, plants, animals, insects, and microorganisms. In recent times research on seaweed is more persistent for extraction of natural bioactive "Sulfated polysaccharides" (SPs). The considerable amount of SP exists in the algae in the form of fucans, fucoidans, carrageenans, ulvan, etc. Major function of SPs is to act as a defensive lattice towards the infective organism. All SPs possess the high potential and possess a broad range of therapeutic applications as antitumor, immunomodulatory, vaccine adjuvant, anti-inflammatory, anticoagulant, antiviral, antiprotozoal, antimicrobial, antilipemic, therapy of regenerative medicine, also in drug delivery and tissue engineering application. This review aims to discuss the biomedicine applications of sulfated polysaccharides from marine seaweeds.

Phytomolecules Repurposed as Covid-19 Inhibitors: Opportunity and Challenges.

The SARS-CoV-2 virus has spread worldwide to cause a full blown pandemic since 2020. To date, several promising synthetic therapeutics are repurposed and vaccines through different stages of clinical trials were approved and being administered, but still the efficacy of the drugs and vaccines are yet to be decoded. This article highlights the importance of traditional medicinal plants and the phytomolecules derived from them, which possess in vitro antiviral and anti-CoV properties and further explores their potential as inhibitors to molecular targets of SARS-CoV-2 that were evaluated by in silico approaches. Botanicals in traditional medicinal systems have been investigated for anti-SARS-CoV-2 activity through in silico and in vitro studies. However, information linking structure of phytomolecules to their antiviral activity is limited. Most phytomolecules with anti-CoV activity were studied for inhibition of the human ACE2 receptor through which the virus enters host cells, and non-structural proteins 3CLpro and PLpro. Although the proteases are ideal anti-CoV targets, information on plant-based inhibitors for the CoV structural proteins, e.g., spike, envelope, membrane, nucleocapsid required further investigations. In absence of scientific evaluations through in vitro and biocompatibility studies, plant-based antivirals fall short as treatment options. Plant-based anti-SARS-CoV-2 therapeutics can be promising alternatives to their synthetic counterparts as they are economical and bear fewer chances of toxicity, side effects, and viral resistance. Our review could provide a systematic overview of the potential phytomolecules which can be repurposed and subjected to further modes of experimental evaluation to qualify for use in treatment and prophylaxis of SARS-CoV-2 infections.

Anti freeze proteins (Afp): Properties, sources and applications - A review.

Extreme cold marine and freshwater temperatures (below 4 °C) induce massive deterioration to the cell membranes of organisms resulting in the formation of ice crystals, consequently causing organelle damage or cell death. One of the adaptive mechanisms organisms have evolved to thrive in cold environments is the production of antifreeze proteins with the functional capabilities to withstand frigid temperatures. Antifreeze proteins are extensively identified in different cold-tolerant species and they facilitate the persistence of cold-adapted organisms by decreasing the freezing point of their body fluids. Various structurally diverse types of antifreeze proteins detected possess the ability to modify ice crystal growth by thermal hysteresis and ice recrystallization inhibition. The unique properties of antifreeze proteins have made them a promising resource in industry, biomedicine, food storage and cryobiology. This review collates the findings of the various studies carried out in the past and the recent developments observed in the properties, functional mechanisms, classification, distinct sources and the ever-increasing applications of antifreeze proteins. This review also summarizes the possibilities of the way forward to identify new avenues of research on anti-freeze proteins.

Chitin derivatives of NAG and chitosan nanoparticles from marine disposal yards and their use for economically feasible fish feed development.

Globally, the disposal of shellfishery waste is a major challenge and causes a risk to the coastal region. For potential development in aquaculture, the use of safe supplements to improve fish production and health is important. Chitosan (CS) used as feed additives for several fish species that enhanced production and immunity. The present study was intended to assess the effect of feed additives N-acetyl-d-glucosamine (NAG) loaded chitosan nanoparticles (CSNPs) on productivity, survival rate, and protein conversion efficiency of Oreochromis niloticus (L.). This is the first report on the effect of CSNPs and NAG loaded CSNPs as feed additives enhanced growth performance and non-specific immunity of O. niloticus. CSNPs and NAG loaded CSNPs were synthesized and characterized by scanning and transmission electron microscope, FT-IR, X-ray diffraction, particle size distribution, and zeta sizer. Fish (15.30 ± 0.23 g) administered diets fortified with 0.0, 0.25, 0.5, 1.0, and 2.0 g CSNPs/kg feed loaded with NAG for 45 d. The diets containing 1.0 g/kg NAG loaded CSNPs enhanced specific growth rate, weight gain, survival rate, respiratory burst, and lysozyme activities of tilapia compared control group. The data shows biologically active CSNPs and NAG loaded CSNPs are potent antimicrobial agents against selected bacterial pathogens. In conclusion, the findings suggested that the dietary supplement containing NAG loaded CSNPs significantly increased immune-modulatory properties, growth performance, and enhanced their disease resistance of Nile tilapia.

Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach.

SARS-CoV-2 virus which caused the global pandemic the Coronavirus Disease- 2019 (COVID-2019) has infected about 1,203,959 patients and brought forth death rate about 64,788 among 206 countries as mentioned by WHO in the month of April 2020. The clinical trials are underway for Remdesivir, an investigational anti-viral drug from Gilead Sciences. Antimalarial drugs such as Chloroquine and Hydroxychloroquine derivatives are being used in emergency cases; however, they are not suitable for patients with conditions like diabetes, hypertension and cardiac issues. The lack of availability of approved treatment for this disease calls forth the scientific community to find novel compounds with the ability to treat it. This paper evaluates the compound Andrographolide from Andrographis paniculata as a potential inhibitor of the main protease of SARS-COV-2 (Mpro) through in silico studies such as molecular docking, target analysis, toxicity prediction and ADME prediction. Andrographolide was docked successfully in the binding site of SARS-CoV-2 Mpro. Computational approaches also predicts this molecule to have good solubility, pharmacodynamics property and target accuracy. This molecule also obeys Lipinski's rule, which makes it a promising compound to pursue further biochemical and cell based assays to explore its potential for use against COVID-19.Communicated by Ramaswamy H. Sarma.

Microbial degradation, spectral analysis and toxicological assessment of malachite green by Streptomyces chrestomyceticus S20.

Malachite green (MG), a triphenylmethane dye is extensively used for coloring silk, aquaculture and textile industries, it has also has been reported toxic to life forms. This study aimed to investigate the biodegradation potential of MG by actinobacteria. The potent actinobacterial strain S20 used in this study was isolated from forest soil (Sabarimala, Kerala, India) and identified as Streptomyces chrestomyceticus based on phenotype and molecular features. Strain S20 degraded MG up to 59.65 ± 0.68% was studied in MSM medium and MG (300 mg l-1) and degradation was increased (90-99%) by additions of 1% glucose and yeast extract into the medium at pH 7. The treated metabolites from MG by S20 characterized by FT-IR and GC-MS. The results showed MG has been degraded into nontoxic compounds evaluated by (1) phytotoxic assay on Vigna radiata, (2) microbial toxicity on Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Streptococcus sp. and Escherichia coli, (3) cytotoxicity assay in a human cell line (MCF 7). The toxicity studies demonstrated that the byproducts from MG degradation by S. chrestomyceticus S20 were no toxic to plants and microbes and less toxic to human cells as compared to the parent MG. Perhaps this is the first work reported on biodegradation of MG by S. chrestomyceticus which could be a potential candidate for the removal of MG from various environments.

Druggability and Binding Site Interaction Studies of Potential Metabolites Isolated from Marine Sponge Aurora globostellata against Human Epidermal Growth Factor Receptor-2.

To study the involvement of compounds stigmasterol and oleic acid isolated from marine sponge Aurora globostellata and docking against the Human Epidermal Growth Factor Receptor-2 in breast cancer. The comparative molecular docking was performed with the natural compounds from marine sponge and the synthetic drugs used in breast cancer treatment against the target HER2. The molecular docking analysis was done using GLIDE in Schrodinger software package. The ADME properties were calculated using the Qikprop. The observation of the common binding site for all the ligands confirms the binding pocket; where the isolated compound Stigmasterol agrees well with the binding residues and thus can be optimized further to arrive at a molecule that has a high binding affinity and low binding constant. The results of the docking studies carried out on HER2 provide an insight for the compound stigmasterol to have drug like properties than oleic acid. These results are supportive to confirm the marine sponges as a better lead for cancer therapeutics.

Molecular Docking of Phytoligands to the viral protein receptor P. monodon Rab7.

The development of shrimp aquaculture has been severely affected by viral diseases resulting in a huge economic burden to the industry. White spot disease (WSD) has caused severe mortality in farmed shrimp in many countries. Globally aquaculture industries face huge economic losses due to rapid spread of White Spot Syndrome Virus (WSSV) disease that can cause 100% mortality in a short period of 3-10 days. In the present study in order to prevent the spread of WSSV disease in shrimps, the receptor, PmRab7 has been chosen as the drug target. Due to the absence of a precise 3D structure of the target, homology-modeling approach was employed to obtain the structure that was validated later. This structure was then used as a template to screen selective phytomolecules as potential antiviral agents and their docking results with the target are analyzed based on their energy scores. Identification of the drug-like molecule obtained from the docking analysis would be used to optimize to a candidate drug. This is expected to play a role of the inhibitor that blocks the binding of the viral protein to the receptor, duly preventing the WSSV disease.

Mycobacteriophage genome database.

UNLABELLED: Mycobacteriophage genome database (MGDB) is an exclusive repository of the 64 completely sequenced mycobacteriophages with annotated information. It is a comprehensive compilation of the various gene parameters captured from several databases pooled together to empower mycobacteriophage researchers. The MGDB (Version No.1.0) comprises of 6086 genes from 64 mycobacteriophages classified into 72 families based on ACLAME database. Manual curation was aided by information available from public databases which was enriched further by analysis. Its web interface allows browsing as well as querying the classification. The main objective is to collect and organize the complexity inherent to mycobacteriophage protein classification in a rational way. The other objective is to browse the existing and new genomes and describe their functional annotation. AVAILABILITY: The database is available for free at http://mpgdb.ibioinformatics.org/mpgdb.php.