This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (... more This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (TR) (PubChem CID:90659753)- identified to be a novel secondary metabolite derived from Streptomyces sp (R2). TR was tested in-vitro against drug resistant TB clinical isolates (n = 49). 94% of DR-TB strains (n = 49) were inhibited by TR at 10μg ml-1. In-vivo safety and efficacy studies showed that 0.005mg kg-1 of TR is toxic to mice, rats and guinea pigs, while 0.001mg kg-1 is safe, infection load did not reduce. TR is a potent DNA intercalator and also targets RecA and methionine aminopeptidases of Mycobacterium. Analogue 47 of TR was designed using in-silico based molecule detoxification approaches and SAR analysis. The multiple targeting nature of the TR brightens the chances of the analogues of TR to be a potent TB therapeutic molecule even though the parental compound is toxic. Analog 47 of TR is proposed to have non-DNA intercalating property and lesser in-vivo toxicity with high f...
A virus enters a living organism and recruits host metabolism to reproduce its own genome and pro... more A virus enters a living organism and recruits host metabolism to reproduce its own genome and proteins. The viral infections are intricate and cannot be completely removed through existing antiviral drugs. For example, the herpes, influenza, hepatitis and human immunodeficiency viruses are a few dreadful ones amongst them. Significant studies are needed to understand the viral entry and their growth in host cells to design effective antivirals. This review emphasizes the range of therapeutical antiviral drugs, inhibitors along with vaccines to fight against viral pathogens, especially for combating COVID-19. Moreover, we have provided the basic and in depth information about viral targets, drugs availability, their mechanisms of action, method of prevention of viral diseases and highlighted the significances of anticoagulants, convalescent plasma for COVID-19 treatment, scientific details of airborne transmission, characteristics of antiviral drug delivery using nanoparticles/carrie...
The unprecedented coronavirus disease 2019 (COVID-19) is triggered by a novel strain of coronavir... more The unprecedented coronavirus disease 2019 (COVID-19) is triggered by a novel strain of coronavirus namely, Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Researchers are working around the clock to control this pandemic and consequent waves of viral reproduction, through repurposing existing drugs as well as designing new vaccines. Several countries have hastened vaccine design and clinical trials to quickly address this outbreak. Currently, more than 250 aspirants against SARS-CoV-2 are in progress, including mRNA-replicating or non-replicating viral vectored-, DNA-, autologous dendritic cell-based-, and inactivated virus-vaccines. Vaccines work by prompting effector mechanisms such as cells/molecules, which target quickly replicating pathogens and neutralize their toxic constituents. Vaccine-stimulated immune effectors include adjuvant, affinity, avidity, affinity maturation, antibodies, antigen-presenting cells, B lymphocytes, carrier protein, CD4+ T-helper cells....
Zymosan (ZM), a naturally occurring insoluble macromolecule obtained from the cell wall of Saccha... more Zymosan (ZM), a naturally occurring insoluble macromolecule obtained from the cell wall of Saccharomyces cerevisiae, is used as a functional food (as dietary fiber), phagocytic stimulus, and immune potentiator. The present study aimed to increase its solubility and evaluate its immunological application. ZM was converted into soluble 6-amino-6-deoxy-β-(1-3)-glucan of a molecular weight of 296 kDa by reduction. Detailed structural characterization of aminated ZM was determined by Fourier transform infrared spectroscopy and two-dimensional NMR analysis (2D, COSY, TOCSY, ROSEY, NOSEY, and HSQC). Aminated ZM was biocompatible with Raw 264.7 macrophage cell lines up to a concentration of 100 μg/mL. Rhodamine tagging revealed that the aminated ZM microparticles were found localized within the nucleus of Raw 264.7 cells. Both native and aminated ZM showed a similar expression pattern of inflammatory genes in Raw 264.7.
Journal of Biomolecular Structure and Dynamics, 2021
Abstract Stem and bark of the tree Terminalia arjuna Wight & Arn. (Combretaceae) has been doc... more Abstract Stem and bark of the tree Terminalia arjuna Wight & Arn. (Combretaceae) has been documented to exhibit therapeutic properties like cardiotonic, anticancer, antiviral, antibacterial, antifungal, hypercholesterolemia, hypolipidemic, and anti-coagulant. Our previous studies have shown that, ethanolic extract of T. arjuna bark exhibits radical scavenging anti-oxidant activity and also effectively inhibited catalase activity. In this study, oleanane triterpenoids type compounds viz., oleanolic acid, arjunolic acid, arjunolitin, arjunetin were isolated from ethanolic bark extract as bio-active compound and their structures were elucidated using 1H, 13C NMR, HR-ESIMS, IR. Of the various compounds, Arjunetin showed significant inhibition of catalase activity as compared to the other compounds. Based on the structural similarity between arjunetin and current antiviral drugs, we propose that arjunetin might exhibit antiviral activity. Molecular docking and molecular dynamics studies showed that arjunetin binds to the binds to key targets of SARS-CoV-2 namely, 3CLpro, PLpro, and RdRp) with a higher binding energy values (3CLpro, −8.4 kcal/mol; PLpro, −7.6 kcal/mol and RdRp, −8.1 kcal/mol) as compared with FDA approved protease inhibitor drugs to Lopinavir (3CLpro, −7.2 kcal/mole and PLpro −7.7 kcal/mole) and Remdesivir (RdRp −7.6 kcal/mole). To further investigate this, we performed 200–500 ns molecular dynamics simulation studies. The results transpired that the binding affinity of Arjunetin is higher than Remdesivir in the RNA binding cavity of RdRp. Based on structural similarity between arjunetin and Saikosaponin (a known antiviral agents) and based on our molecular docking and molecular dynamic simulation studies, we propose that arjunetin can be a promising drug candidate against Covid-19. Communicated by Ramaswamy H. Sarma
ABSTRACT Glucans are biopolymers made up of repeating units of D-glucose and are of biological or... more ABSTRACT Glucans are biopolymers made up of repeating units of D-glucose and are of biological origin with varying molecular weights. The differences in their linkage, chemical structure, branching and substitutions afford them unique properties. This review deals with the production and applications of α and β glucans from different sources such as cereal, yeast, fungi, plants, bacteria, and current global manufactures and their market value. The market value of glucans is more than 200 M US$ and expected to grow rapidly in medical, food and cosmetic industries. Applications of some of the industrially important α glucans, namely, dextran, amylopectin, glycogen, pullulan, amylose and β glucans; namely cereal glucan, yeast glucan, curdlan, laminarin, microbial cellulose, lentinan are described. Chemical modification of glucans can help in improving their properties for wider applications. A thorough understanding of these biopolymers could expand their applications in newer fields and may help in replacing some of the synthetic polymers which have several associated waste disposal and toxicity problems. GRAPHICAL ABSTRACT
Stem and bark of the tree Terminalia arjuna Wight &Arn. (Combretaceae) has been documented to exh... more Stem and bark of the tree Terminalia arjuna Wight &Arn. (Combretaceae) has been documented to exhibit therapeutic properties like cardiotonic, anticancer, antiviral, antibacterial, antifungal, hypocholsteremic, hypolipidemic and anti-coagulant. In previous studies, ethanolic extract of T.arjunabark effectively inhibited catalase activity along with demonstration of DPPH radical scavenging activity. Further,four known oleananetriterpenoids type compounds viz., oleanolic acid, arjunolic acid, arjunolitin, arjunetin were isolated from ethaolic bark extract and the structures of which were elucidated using 1 H, 13C NMR, HR-ESIMS, IR and compared with literature data. Of the various compounds, Arjunetin showed significant inhibition of catalase activity as compared to the other compounds and most probably conferring antibacterial and antiviral property of the extract. In the present study, considering the currently on going viral pandemic of SARS-CoV-2 and the need for an effective antiv...
This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (... more This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (TR) (PubChem CID:90659753)- identified to be a novel secondary metabolite derived from Streptomyces sp (R2). TR was tested in-vitro against drug resistant TB clinical isolates (n = 49). 94% of DR-TB strains (n = 49) were inhibited by TR at 10μg ml-1. In-vivo safety and efficacy studies showed that 0.005mg kg-1 of TR is toxic to mice, rats and guinea pigs, while 0.001mg kg-1 is safe, infection load did not reduce. TR is a potent DNA intercalator and also targets RecA and methionine aminopeptidases of Mycobacterium. Analogue 47 of TR was designed using in-silico based molecule detoxification approaches and SAR analysis. The multiple targeting nature of the TR brightens the chances of the analogues of TR to be a potent TB therapeutic molecule even though the parental compound is toxic. Analog 47 of TR is proposed to have non-DNA intercalating property and lesser in-vivo toxicity with high f...
A virus enters a living organism and recruits host metabolism to reproduce its own genome and pro... more A virus enters a living organism and recruits host metabolism to reproduce its own genome and proteins. The viral infections are intricate and cannot be completely removed through existing antiviral drugs. For example, the herpes, influenza, hepatitis and human immunodeficiency viruses are a few dreadful ones amongst them. Significant studies are needed to understand the viral entry and their growth in host cells to design effective antivirals. This review emphasizes the range of therapeutical antiviral drugs, inhibitors along with vaccines to fight against viral pathogens, especially for combating COVID-19. Moreover, we have provided the basic and in depth information about viral targets, drugs availability, their mechanisms of action, method of prevention of viral diseases and highlighted the significances of anticoagulants, convalescent plasma for COVID-19 treatment, scientific details of airborne transmission, characteristics of antiviral drug delivery using nanoparticles/carrie...
The unprecedented coronavirus disease 2019 (COVID-19) is triggered by a novel strain of coronavir... more The unprecedented coronavirus disease 2019 (COVID-19) is triggered by a novel strain of coronavirus namely, Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Researchers are working around the clock to control this pandemic and consequent waves of viral reproduction, through repurposing existing drugs as well as designing new vaccines. Several countries have hastened vaccine design and clinical trials to quickly address this outbreak. Currently, more than 250 aspirants against SARS-CoV-2 are in progress, including mRNA-replicating or non-replicating viral vectored-, DNA-, autologous dendritic cell-based-, and inactivated virus-vaccines. Vaccines work by prompting effector mechanisms such as cells/molecules, which target quickly replicating pathogens and neutralize their toxic constituents. Vaccine-stimulated immune effectors include adjuvant, affinity, avidity, affinity maturation, antibodies, antigen-presenting cells, B lymphocytes, carrier protein, CD4+ T-helper cells....
Zymosan (ZM), a naturally occurring insoluble macromolecule obtained from the cell wall of Saccha... more Zymosan (ZM), a naturally occurring insoluble macromolecule obtained from the cell wall of Saccharomyces cerevisiae, is used as a functional food (as dietary fiber), phagocytic stimulus, and immune potentiator. The present study aimed to increase its solubility and evaluate its immunological application. ZM was converted into soluble 6-amino-6-deoxy-β-(1-3)-glucan of a molecular weight of 296 kDa by reduction. Detailed structural characterization of aminated ZM was determined by Fourier transform infrared spectroscopy and two-dimensional NMR analysis (2D, COSY, TOCSY, ROSEY, NOSEY, and HSQC). Aminated ZM was biocompatible with Raw 264.7 macrophage cell lines up to a concentration of 100 μg/mL. Rhodamine tagging revealed that the aminated ZM microparticles were found localized within the nucleus of Raw 264.7 cells. Both native and aminated ZM showed a similar expression pattern of inflammatory genes in Raw 264.7.
Journal of Biomolecular Structure and Dynamics, 2021
Abstract Stem and bark of the tree Terminalia arjuna Wight & Arn. (Combretaceae) has been doc... more Abstract Stem and bark of the tree Terminalia arjuna Wight & Arn. (Combretaceae) has been documented to exhibit therapeutic properties like cardiotonic, anticancer, antiviral, antibacterial, antifungal, hypercholesterolemia, hypolipidemic, and anti-coagulant. Our previous studies have shown that, ethanolic extract of T. arjuna bark exhibits radical scavenging anti-oxidant activity and also effectively inhibited catalase activity. In this study, oleanane triterpenoids type compounds viz., oleanolic acid, arjunolic acid, arjunolitin, arjunetin were isolated from ethanolic bark extract as bio-active compound and their structures were elucidated using 1H, 13C NMR, HR-ESIMS, IR. Of the various compounds, Arjunetin showed significant inhibition of catalase activity as compared to the other compounds. Based on the structural similarity between arjunetin and current antiviral drugs, we propose that arjunetin might exhibit antiviral activity. Molecular docking and molecular dynamics studies showed that arjunetin binds to the binds to key targets of SARS-CoV-2 namely, 3CLpro, PLpro, and RdRp) with a higher binding energy values (3CLpro, −8.4 kcal/mol; PLpro, −7.6 kcal/mol and RdRp, −8.1 kcal/mol) as compared with FDA approved protease inhibitor drugs to Lopinavir (3CLpro, −7.2 kcal/mole and PLpro −7.7 kcal/mole) and Remdesivir (RdRp −7.6 kcal/mole). To further investigate this, we performed 200–500 ns molecular dynamics simulation studies. The results transpired that the binding affinity of Arjunetin is higher than Remdesivir in the RNA binding cavity of RdRp. Based on structural similarity between arjunetin and Saikosaponin (a known antiviral agents) and based on our molecular docking and molecular dynamic simulation studies, we propose that arjunetin can be a promising drug candidate against Covid-19. Communicated by Ramaswamy H. Sarma
ABSTRACT Glucans are biopolymers made up of repeating units of D-glucose and are of biological or... more ABSTRACT Glucans are biopolymers made up of repeating units of D-glucose and are of biological origin with varying molecular weights. The differences in their linkage, chemical structure, branching and substitutions afford them unique properties. This review deals with the production and applications of α and β glucans from different sources such as cereal, yeast, fungi, plants, bacteria, and current global manufactures and their market value. The market value of glucans is more than 200 M US$ and expected to grow rapidly in medical, food and cosmetic industries. Applications of some of the industrially important α glucans, namely, dextran, amylopectin, glycogen, pullulan, amylose and β glucans; namely cereal glucan, yeast glucan, curdlan, laminarin, microbial cellulose, lentinan are described. Chemical modification of glucans can help in improving their properties for wider applications. A thorough understanding of these biopolymers could expand their applications in newer fields and may help in replacing some of the synthetic polymers which have several associated waste disposal and toxicity problems. GRAPHICAL ABSTRACT
Stem and bark of the tree Terminalia arjuna Wight &Arn. (Combretaceae) has been documented to exh... more Stem and bark of the tree Terminalia arjuna Wight &Arn. (Combretaceae) has been documented to exhibit therapeutic properties like cardiotonic, anticancer, antiviral, antibacterial, antifungal, hypocholsteremic, hypolipidemic and anti-coagulant. In previous studies, ethanolic extract of T.arjunabark effectively inhibited catalase activity along with demonstration of DPPH radical scavenging activity. Further,four known oleananetriterpenoids type compounds viz., oleanolic acid, arjunolic acid, arjunolitin, arjunetin were isolated from ethaolic bark extract and the structures of which were elucidated using 1 H, 13C NMR, HR-ESIMS, IR and compared with literature data. Of the various compounds, Arjunetin showed significant inhibition of catalase activity as compared to the other compounds and most probably conferring antibacterial and antiviral property of the extract. In the present study, considering the currently on going viral pandemic of SARS-CoV-2 and the need for an effective antiv...
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