Ascertaining variations in the activity of larval midgut enzymes of Helicoverpa armigera by dietary emamectin benzoate through biochemical and in silico docking study.

Helicoverpa armigera, a ubiquitous polyphagous pest, poses a significant threat to global agriculture, causing substantial economic losses and demonstrating resistance to synthetic pesticides. This study investigates the potential of emamectin benzoate (EMB), an avermectin derivative, as an effective control agent against H. armigera. The larvae of the NBII-MP-NOC-01 strain of H. armigera were reared on an artificial diet. The impact of dietary EMB was examined on four midgut enzymes; alanine aminotransferase (ALT), aspartate aminotransferase (AST), acid phosphatase (ACP), and alkaline phosphatase (ALP). Results showed a dose-dependent and time-dependent reduction in ALT and AST activity, while an initial increase and subsequent decline in ACP and ALP activity at higher EMB concentrations. Computational modelling of enzyme structures and molecular docking studies revealed differential binding of EMB with the midgut enzymes. The strongest interaction was observed between EMB and ALT residues, contrasting with weakest interactions observed with AST. The study also showed that decreased activity of transaminases in H. armigera caused by EMB may be because of stability-activity trade-off, while in phosphatases reverse may be the case. This research provides crucial insights into the biochemical responses and the intricate insecticide-enzyme interactions in H. armigera caused by EMB exposure. This study lays the foundation for further research aimed at developing environmentally friendly approaches for managing H. armigera, addressing the challenges associated with conventional pesticides.

AMPA GluA2 subunit competitive inhibitors for PICK1 PDZ domain: Pharmacophore-based virtual screening, molecular docking, molecular dynamics simulation, and ADME studies.

PICK1 (Protein interacting with C kinase-1) plays a key role in the regulation of intracellular trafficking of AMPA GluA2 subunit that is linked with synaptic plasticity. PICK1 is a scaffolding protein and binds numerous proteins through its PDZ domain. Research showed that synaptic plasticity is altered upon disrupting the GluA2-PDZ interactions. Inhibiting PDZ and GluA2 binding lead to beneficial effects in the cure of neurological diseases thus, targeting PDZ domain is proposed as a novel therapeutic target in such diseases. For this, various classes of synthetic peptides were tested. Though small organic molecules have been utilized to prevent these interactions, the number of such molecules is inadequate. Hence, in this study, ten molecular libraries containing large number of molecules were screened against the PDZ domain using pharmacophore-based virtual screening to find the best hits for the PDZ domain. Molecular docking and molecular dynamics simulation studies revealed that Hit_II is a potent inhibitor for the PDZ domain and confirm the allosteric nature of Hit_III. Additionally, ADME analysis suggests the drug-likeness of both Hit_II and Hit_III. This study suggests that tested hits may have potency against the PDZ domain and can be considered effective to treat neurological disorders.Communicated by Ramaswamy H. Sarma.

In silico characterization of mutations circulating in SARS-CoV-2 structural proteins.

SARS-CoV-2 has recently emerged as a pandemic that has caused more than 2.4 million deaths worldwide. Since the onset of infections, several full-length sequences of viral genome have been made available which have been used to gain insights into viral dynamics. We utilised a meta-data driven comparative analysis tool for sequences (Meta-CATS) algorithm to identify mutations in 829 SARS-CoV-2 genomes from around the world. The algorithm predicted sixty-one mutations among SARS-CoV-2 genomes. We observed that most of the mutations were concentrated around three protein coding genes viz nsp3 (non-structural protein 3), RdRp (RNA-directed RNA polymerase) and Nucleocapsid (N) proteins of SARS-CoV-2. We used various computational tools including normal mode analysis (NMA), C-α discrete molecular dynamics (DMD) and all-atom molecular dynamic simulations (MD) to study the effect of mutations on functionality, stability and flexibility of SARS-CoV-2 structural proteins including envelope (E), N and spike (S) proteins. PredictSNP predictor suggested that four mutations (L37H in E, R203K and P344S in N and D614G in S) out of seven were predicted to be neutral whilst the remaining ones (P13L, S197L and G204R in N) were predicted to be deleterious in nature thereby impacting protein functionality. NMA, C-α DMD and all-atom MD suggested some mutations to have stabilizing roles (P13L, S197L and R203K in N protein) where remaining ones were predicted to destabilize mutant protein. In summary, we identified significant mutations in SARS-CoV-2 genomes as well as used computational approaches to further characterize the possible effect of highly significant mutations on SARS-CoV-2 structural proteins.Communicated by Ramaswamy H. Sarma.

Efficacy of intra-umbilical oxytocin in the management of retained placenta: a randomized controlled trial.

AIM: Retained placenta is an important cause of maternal mortality. The present study was aimed to determine the efficacy of umbilical injection of oxytocin as a treatment modality in this condition. MATERIAL AND METHODS: This was a single-center randomized controlled trial incorporating 58 women with retained placenta of more than 30 min, equally distributed into two study arms of intra-umbilical injection of oxytocin (50 IU oxytocin diluted with normal saline [NS] to a total volume 30 mL) and intra-umbilical injection of NS (30 mL). Primary outcome was expulsion of the placenta within 30 min following intervention. All the data were analyzed on an intention-to-treat basis. RESULTS: The success rate in the intra-umbilical oxytocin group was 51.72% compared to 20.69% in the control arm. This difference in the primary outcome was statistically significant with a P-value<0.05 (P=0.014) favoring intra-umbilical oxytocin infusion with an efficacy rate of 1.5 and a number-needed-to-treat of 3. The peripartum bleeding complications were more in the NS group with a statistically higher (P<0.001) requirement of extra oxytocin to control post-partum bleeding. There were no differences between the two groups in respect to other secondary outcomes, such as post-partum fever, antibiotic requirement and hospital stay. CONCLUSION: Umbilical vein injection of 50IU oxytocin in 30mL of NS delivered effectively via the umbilical cord with milking in cases of retained placenta seems a simple and promising technique to reduce the incidence of a potentially morbid procedure and other complications.