Lipophilic bioactive compounds from thermophilic cyanobacterium Leptolyngbya sp. HNBGU-004: Implications for countering VRSA resistance.

Extremophiles thrive in extreme conditions, showcasing rich and unexplored diversity. This resilience hints at the existence of novel biochemical pathways and unique bioactive compounds. In contrast, the issue of drug resistance and excessive misuse of antibiotics in various settings, such as healthcare, agriculture, and veterinary medicine, has contributed to the emergence and spread of drug-resistant microorganisms. In the present research, Leptolyngbya sp. HNBGU-004, was obtained from an extreme location, a hot water spring in the Garhwal Himalayan region of India. The lipophilic fraction derived from Leptolyngbya sp. HNBGU-004 exhibited significant inhibitory effects against vancomycin-resistant Staphylococcus aureus (VRSA), displaying a bactericidal concentration of 0.5 mg mL-1. Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis of the lipophilic extract unveiled the major constituents. Leptolyngbya sp. HNBGU-004 holds significant promise as a primary source of potent anti-vancomycin-resistant S. aureus components. These findings emphasize the importance of Leptolyngbya sp. HNBGU-004 as a foundational source for use as both a synergistic and alternative agent against VRSA.

Revisiting scrub typhus: A neglected tropical disease.

Scrub typhus is an under diagnosed re-emerging vector borne disease caused by an intracellular gram negative bacteria, Orientia. The disease is commonly prevalent in rural and hilly areas of Tsutsugumashi triangle. The diagnosis of the disease is very challenging due to similarity of its early symptoms with other febrile illnesses, like dengue and COVID 19, as well as non-availability of rapid, reliable and cost-effective methods. Moreover, the diverse clinical presentation in severe cases make it significant health problem. The occupational and behavioral risks responsible for the transmission lead to urgent need of vaccine development against the disease. The complete knowledge about its pathogenesis and the interaction with host's immune cells may help the scientists in developing the appropriate diagnostic methods as well as the vaccines.

Orchestrating the fecal microbiota transplantation: Current technological advancements and potential biomedical application.

Fecal microbiota transplantation (FMT) has been proved to be an effective treatment for gastrointestinal disorders caused due to microbial disbalance. Nowadays, this approach is being used to treat extragastrointestinal conditions like metabolic and neurological disorders, which are considered to have their provenance in microbial dysbiosis in the intestine. Even though case studies and clinical trials have demonstrated the potential of FMT in treating a variety of ailments, safety and ethical concerns must be answered before the technique is widely used to the community's overall benefit. From this perspective, it is not unexpected that techniques for altering gut microbiota may represent a form of medication whose potential has not yet been thoroughly addressed. This review intends to gather data on recent developments in FMT and its safety, constraints, and ethical considerations.

Cytokinin biosynthesis in cyanobacteria: Insights for crop improvement.

Cytokinins, a type of phytohormones that induce division of cytoplasm, have considerable value in agriculture due to their influences on several physiological processes of plants such as morphogenesis, development of chloroplast, seed dormancy, leaf senescence, etc. Previously, it was assumed that plants obtain cytokinin from the soil produced by microbes as these hormones were first discovered in soil-inhabiting bacteria i.e., Agrobacterium tumefaciens. Later, the cytokinin biosynthesis gene, i.e., ipt gene, has been reported in plants too. Though plants synthesize cytokinins, several studies have reported that the exogenous application of cytokinins has numerous beneficial effects including the acceleration of plant growth and boosting economic yield. Cyanobacteria may be employed in the soil not only as the source of cytokinins but also as the source of other plant growth-promoting metabolites. These organisms biosynthesize the cytokinins using the enzyme isopentenyl transferases (IPTs) in a fashion similar to the plants; however, there are few differences in the biosynthesis mechanism of cytokinins in cyanobacteria and plants. Cytokinins are important for the establishment of interaction between plants and cyanobacteria as evidenced by gene knockout experiments. These hormones are also helpful in alleviating the adverse effects of abiotic stresses on plant development. Cyanobacterial supplements in the field result in the induction of adventitious roots and shoots on petiolar as well as internodal segments. The leaf, root, and stem explants of certain plants exhibited successful regeneration when treated with cyanobacterial extract/cell suspension. These successful regeneration practices mark the way of cyanobacterial deployment in the field as a great move toward the goal of sustainable agriculture.

Computational Analysis Reveals Monomethylated Triazolopyrimidine as a Novel Inhibitor of SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp).

The human population is still facing appalling conditions due to several outbreaks of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus. The absence of specific drugs, appropriate vaccines for mutants, and knowledge of potential therapeutic agents makes this situation more difficult. Several 1, 2, 4-triazolo [1, 5-a] pyrimidine (TP)-derivative compounds were comprehensively studied for antiviral activities against RNA polymerase of HIV, HCV, and influenza viruses, and showed immense pharmacological interest. Therefore, TP-derivative compounds can be repurposed against the RNA-dependent RNA polymerase (RdRp) protein of SARS-CoV-2. In this study, a meta-analysis was performed to ensure the genomic variability and stability of the SARS-CoV-2 RdRp protein. The molecular docking of natural and synthetic TP compounds to RdRp and molecular dynamic (MD) simulations were performed to analyse the dynamic behaviour of TP compounds at the active site of the RdRp protein. TP compounds were also docked against other non-structural proteins (NSP1, NSP2, NSP3, NSP5, NSP8, NSP13, and NSP15) of SARS-CoV-2. Furthermore, the inhibition potential of TP compounds was compared with Remdesivir and Favipiravir drugs as a positive control. Additionally, TP compounds were analysed for inhibitory activity against SARS-CoV RdRp protein. This study demonstrates that TP analogues (monomethylated triazolopyrimidine and essramycin) represent potential lead molecules for designing an effective inhibitor to control viral replication. Furthermore, in vitro and in vivo studies will strengthen the use of these inhibitors as suitable drug candidates against SARS-CoV-2.

Cancer and diabetes: the interlinking metabolic pathways and repurposing actions of antidiabetic drugs.

Cancers are regarded as one of the main causes of death and result in high health burden worldwide. The management of cancer include chemotherapy, surgery and radiotherapy. The chemotherapy, which involves the use of chemical agents with cytotoxic actions is utilised as a single treatment or combined treatment. However, these managements of cancer such as chemotherapy poses some setbacks such as cytotoxicity on normal cells and the problem of anticancer drug resistance. Therefore, the use of other therapeutic agents such as antidiabetic drugs is one of the alternative interventions used in addressing some of the limitations in the use of anticancer agents. Antidiabetic drugs such as sulfonylureas, biguanides and thiazolidinediones showed beneficial and repurposing actions in the management of cancer, thus, the activities of these drugs against cancer is attributed to some of the metabolic links between the two disorders and these includes hyperglycaemia, hyperinsulinemia, inflammation, and oxidative stress as well as obesity. Furthermore, some studies showed that the use of antidiabetic drugs could serve as risk factors for the development of cancerous cells particularly pancreatic cancer. However, the beneficial role of these chemical agents overweighs their detrimental actions in cancer management. Hence, the present review indicates the metabolic links between cancer and diabetes and the mechanistic actions of antidiabetic drugs in the management of cancers.

Anti-enterococcal and anti-oxidative potential of a thermophilic cyanobacterium, Leptolyngbya sp. HNBGU 003.

Enterococci, the opportunistic pathogens, pose several serious and life-threatening infections such as urinary tract infections, sepsis, and endocarditis. The situation is worsening due to the development of drug resistance in these pathogens against several antibiotics. The addition of anti-enterococcal compounds with antioxidant activity in fermented and packaged food may help prevent the transmission of food-borne enterococcal infections. Scientists are in continuous search of such compounds from various sources. Hence, the present study has tested the diethyl ether extracts of thermophilic cyanobacteria, selected based on a previous study, against the multidrug-resistant and -sensitive strains of Enterococcus faecium. Out of the eleven tested extracts, 72% have shown anti-enterococcal activity against both strains. Among the extracts with anti-enterococcal activity, the diethyl ether extract of Leptolyngbya sp. (DEEL-3) inhibited the growth of VRE in a dose-dependent manner with a minimum inhibitory concentration of 2.0 mg mL-1. The DEEL-3 has also shown its antioxidant potential in terms of DPPH scavenging with an IC50 of 3.16 mg mL-1. The organism was named Leptolyngbya sp. HNBGU 003 based on 16SrRNA sequence homology analysis and morphological features. Further, the GC-MS analysis of the DEEL-3 has revealed the predominance of two phenolic compounds, phenol, 2,4-bis(1,1-dimethylethyl)-, phosphite (3:1) and tris(2,4-di-tert-butylphenyl) phosphate, in it. Thus, the anti-enterococcal and antioxidant activity of DEEL-3 may be attributed to these phenolics, which may be isolated and developed as food additives.

Micro-RNA: The darkhorse of cancer.

The discovery of micro RNAs (miRNA) in cancer has opened up new vistas for researchers in recent years. Micro RNAs area set of small, endogenous, highly conserved, non-coding RNAs that control the expression of about 30% genes at post-transcriptional levels. Typically, microRNAs impede the translation and stability of messenger RNAs (mRNA), control genes associated with cellular processes namely inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and migration. Compelling findings revealed that miRNA mutations or disruption correspond to diverse human cancers and suggest that miRNAs can function as tumor suppressors or oncogenes. Here we summarize the literature on these master regulators in clinical settings from last three decades as both abrupt cancer therapeutics and as an approach to sensitize tumors to chemotherapy. This review highlights (I) the prevailing perception of miRNA genomics, biogenesis, as well as function; (II) the significant advancements in regulatory mechanisms in the expression of carcinogenic genes; and (III) explains, how miRNA is utilized as a diagnostic and prognostic biomarker for the disease stage indicating survival as well as therapeutic targets in cancer.

Molecular targets and system biology approaches for drug repurposing against SARS-CoV-2.

BACKGROUND: COVID-19, a pandemic declared by WHO, has infected about 39.5 million and killed about 1.1 million people throughout the world. There is the urgent need of more studies to identify the novel drug targets and the drug candidates against it to handle the situation. MAIN BODY: To virtually screen various drugs against SARS-CoV-2, the scientists need the detail information about the various drug targets identified till date. The present review provides the information about almost all the drug targets, including structural and non-structural proteins of virus as well as host cell surface receptors, that can be used for virtual screening of drugs. Moreover, this review also focuses on the different network analysis tools that have been used for the identification of new drug targets and candidate repurposable drugs against SARS-CoV-2. CONCLUSION: This review provides important insights of various drug targets and the network analysis tools to young bioinformaticians and will help in creating pace to the drug repurposing strategy for COVID-19 disease.

Aeruginosins from a Microcystis sp. bloom material collected in Varanasi, India.

Two novel biologically active short peptides, aeruginosins IN608 and IN652, were isolated from the cyanobacterium Microcystis sp. strain BHU006, which was collected from Durgakund water reservoir in Varanasi, India. Aeruginosins IN608 and IN652 are linear modified peptides containing four building blocks, one of which is the arogenate-derived modified amino acid 2-carboxy-6-hydroxyoctahydroindole. Aeruginosin IN608 and aeruginosin IN652 inhibit the activity of the proteolytic enzyme trypsin with IC50's of 4.3 and 4.1 µM, respectively.

Cyanobacteria: an emerging source for drug discovery.

The c group of Gram-negative gliding bacteria, has a long history of cosmopolitan occurrence. It has great biodiversity despite the absence of sexual reproduction. This wide biodiversity may be reflected in the wide spectrum of its secondary metabolites. These cyanobacterial secondary metabolites are biosynthesized by a variety of routes, notably by non-ribosomal peptide synthetase or polyketide synthetase systems, and show a wide range of biological activities including anticancer, antibacterial, antiviral and protease inhibition activities. This high degree of chemical diversity in cyanobacterial secondary metabolites may thus constitute a prolific source of new entities leading to the development of new pharmaceuticals.