Era, a widely known GTP binding protein found in many organisms including prokaryotes and eukaryotes and plays a significant role in many fundamental cellular processes like cell growth, differentiation and signaling. In Mycobacterium tuberculosis (Mtb) H₃₇Rv, Era protein had been proved as a GTPase protein but its structural and functional insights are still lacking. Through comparative analysis, structural modeling, docking and using various bioinformatic tools, a detailed investigation of Era was carried out to deduce the structure, function and residues involved in the activity of the protein. Intriguingly, docking results revealed high binding affinity of Era not only with GTP but also with ATP. Myristoylation modifications and phosphorylations on Era were predicted to possibly aid in regulating Era activity and localization; and also the role of Era in translation regulation was foreseen by showing its association with 16s rRNA. Moreover, point mutation of Era residues revealed the effect of W288G and K19G in highly destabilizing the protein structure and activity. Additionally, Era protein was docked with 25 GTPase/ATPase inhibitors, where, Dynasore inhibitor showed the highest affinity for the protein’s GTP binding sites and can be used for further drug trials to inhibit growth of mycobacteria. MtEra protein carries five GTP binding motifs (G1, G2, G3, G4 and G5) and one KH domain for RNA binding.Multifunctional role of MtEra predicted in processes like catabolic, metabolic and ribosome biogenesis.Point mutation analysis showed the importance of tryptophan (W) and lysine (K) residues at position 288 and 19 in stability and activity of the protein, respectively.Dynasore inhibitor showed the highest binding energy of −9 kcal/mol for MtEra. MtEra protein carries five GTP binding motifs (G1, G2, G3, G4 and G5) and one KH domain for RNA binding. Multifunctional role of MtEra predicted in processes like catabolic, metabolic and ribosome biogenesis. Point mutation analysis showed the importance of tryptophan (W) and lysine (K) residues at position 288 and 19 in stability and activity of the protein, respectively. Dynasore inhibitor showed the highest binding energy of −9 kcal/mol for MtEra.

Era, a widely known GTP binding protein found in many organisms including prokaryotes and eukaryotes and plays a significant role in many fundamental cellular processes like cell growth, differentiation and signaling. In Mycobacterium tuberculosis (Mtb) H₃₇Rv, Era protein had been proved as a GTPase protein but its structural and functional insights are still lacking. Through comparative analysis, structural modeling, docking and using various bioinformatic tools, a detailed investigation of Era was carried out to deduce the structure, function and residues involved in the activity of the protein. Intriguingly, docking results revealed high binding affinity of Era not only with GTP but also with ATP. Myristoylation modifications and phosphorylations on Era were predicted to possibly aid in regulating Era activity and localization; and also the role of Era in translation regulation was foreseen by showing its association with 16s rRNA. Moreover, point mutation of Era residues revealed the effect of W288G and K19G in highly destabilizing the protein structure and activity. Additionally, Era protein was docked with 25 GTPase/ATPase inhibitors, where, Dynasore inhibitor showed the highest affinity for the protein’s GTP binding sites and can be used for further drug trials to inhibit growth of mycobacteria. MtEra protein carries five GTP binding motifs (G1, G2, G3, G4 and G5) and one KH domain for RNA binding.Multifunctional role of MtEra predicted in processes like catabolic, metabolic and ribosome biogenesis.Point mutation analysis showed the importance of tryptophan (W) and lysine (K) residues at position 288 and 19 in stability and activity of the protein, respectively.Dynasore inhibitor showed the highest binding energy of −9 kcal/mol for MtEra. MtEra protein carries five GTP binding motifs (G1, G2, G3, G4 and G5) and one KH domain for RNA binding. Multifunctional role of MtEra predicted in processes like catabolic, metabolic and ribosome biogenesis. Point mutation analysis showed the importance of tryptophan (W) and lysine (K) residues at position 288 and 19 in stability and activity of the protein, respectively. Dynasore inhibitor showed the highest binding energy of −9 kcal/mol for MtEra.

Several generations of anti-epileptic drugs (AEDs) are available but have several associated side effects apart from a limited success rate. Drug repositioning strategies have gained importance in the last two decades owing to lower failure rates and economic burden. Drugs with similar side effect profiles may share a common mechanism of action and thus can be linked to other disease treatments. The present study was carried out to identify the newly approved drug candidate(s) as AEDs using clinical side-effects drug repositioning strategy. The clinical side effect similarity of drugs available in the SIDER v4.1 database was estimated against common side effects of 5 major marketed AEDs, using the ‘dplyr’ package library in the R. Further drugs were filtered based on Blood Brain Barrier permeability prediction and FDA-approval status. Molecular docking studies were performed for selected 26 hits (drugs) against previously identified epilepsy target receptors: Voltage-gated sodium channel α2 (Nav1.2), GABA receptor α1-β1 (GABAr α1-β1), and Voltage-gated calcium channel α-1 G (Cav3.1). Only 2 drugs (Ziprasidone and Paroxetine) showed better binding affinities against studied epilepsy receptors Nav1.2, GABAr α1-β1, and Cav3.1, than their corresponding standard AEDs, i.e. Carbamazepine, Clonazepam, and Pregabalin, respectively. Ziprasidone reportedly showed seizure-like symptoms in ∼3% of patients and was hence omitted from further study. The MDS study of docked complexes of Paroxetine with selected epilepsy target receptors showed stable RMSD values and better interaction energies. The study reveals Paroxetine as a potential candidate to be repurposed for 1st line epileptic seizure medication. Communicated by Ramaswamy H. Sarma

Several generations of anti-epileptic drugs (AEDs) are available but have several associated side effects apart from a limited success rate. Drug repositioning strategies have gained importance in the last two decades owing to lower failure rates and economic burden. Drugs with similar side effect profiles may share a common mechanism of action and thus can be linked to other disease treatments. The present study was carried out to identify the newly approved drug candidate(s) as AEDs using clinical side-effects drug repositioning strategy. The clinical side effect similarity of drugs available in the SIDER v4.1 database was estimated against common side effects of 5 major marketed AEDs, using the ‘dplyr’ package library in the R. Further drugs were filtered based on Blood Brain Barrier permeability prediction and FDA-approval status. Molecular docking studies were performed for selected 26 hits (drugs) against previously identified epilepsy target receptors: Voltage-gated sodium channel α2 (Nav1.2), GABA receptor α1-β1 (GABAr α1-β1), and Voltage-gated calcium channel α-1 G (Cav3.1). Only 2 drugs (Ziprasidone and Paroxetine) showed better binding affinities against studied epilepsy receptors Nav1.2, GABAr α1-β1, and Cav3.1, than their corresponding standard AEDs, i.e. Carbamazepine, Clonazepam, and Pregabalin, respectively. Ziprasidone reportedly showed seizure-like symptoms in ∼3% of patients and was hence omitted from further study. The MDS study of docked complexes of Paroxetine with selected epilepsy target receptors showed stable RMSD values and better interaction energies. The study reveals Paroxetine as a potential candidate to be repurposed for 1st line epileptic seizure medication. Communicated by Ramaswamy H. Sarma

Tuberculosis (TB) is a fast spreading; transmissible disease caused by the Mycobacterium tuberculosis (M. tuberculosis). M. tuberculosis has a high death rate in its endemic regions due to a lack of appropriate treatment and preventative measures. We have used a vaccinomics strategy to create an effective multi-epitope vaccine against M. tuberculosis. The antigenic proteins with the highest antigenicity were utilised to predict cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and linear B-lymphocyte (LBL) epitopes. CTL and HTL epitopes were covered in 99.97% of the population. Seven epitopes each of CTL, HTL, and LBL were ultimately selected and utilised to develop a multi-epitope vaccine. A vaccine design was developed by combining these epitopes with suitable linkers and LprG adjuvant. The vaccine chimera was revealed to be highly immunogenic, non-allergenic, and non-toxic. To ensure a better expression within the Escherichia coli K12 (E. coli K12) host system, codon adaptation and in silico cloning were accomplished. Following that, various validation studies were conducted, including molecular docking, molecular dynamics simulation, and immunological simulation, all of which indicated that the designed vaccine would be stable in the biological environment and effective against M. tuberculosis infection. The immune simulation revealed higher levels of T-cell and B-cell activity, which corresponded to the actual immune response. Exposure simulations were repeated several times, resulting in increased clonal selection and faster antigen clearance. These results suggest that, if proposed vaccine chimera would test both in-vitro and in-vivo, it could be a viable treatment and preventive strategy for TB. Communicated by Ramaswamy H. Sarma

Tuberculosis (TB) is a fast spreading; transmissible disease caused by the Mycobacterium tuberculosis (M. tuberculosis). M. tuberculosis has a high death rate in its endemic regions due to a lack of appropriate treatment and preventative measures. We have used a vaccinomics strategy to create an effective multi-epitope vaccine against M. tuberculosis. The antigenic proteins with the highest antigenicity were utilised to predict cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and linear B-lymphocyte (LBL) epitopes. CTL and HTL epitopes were covered in 99.97% of the population. Seven epitopes each of CTL, HTL, and LBL were ultimately selected and utilised to develop a multi-epitope vaccine. A vaccine design was developed by combining these epitopes with suitable linkers and LprG adjuvant. The vaccine chimera was revealed to be highly immunogenic, non-allergenic, and non-toxic. To ensure a better expression within the Escherichia coli K12 (E. coli K12) host system, codon adaptation and in silico cloning were accomplished. Following that, various validation studies were conducted, including molecular docking, molecular dynamics simulation, and immunological simulation, all of which indicated that the designed vaccine would be stable in the biological environment and effective against M. tuberculosis infection. The immune simulation revealed higher levels of T-cell and B-cell activity, which corresponded to the actual immune response. Exposure simulations were repeated several times, resulting in increased clonal selection and faster antigen clearance. These results suggest that, if proposed vaccine chimera would test both in-vitro and in-vivo, it could be a viable treatment and preventive strategy for TB. Communicated by Ramaswamy H. Sarma

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

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An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.