Computational analysis of affinity dynamics between the variants of SARS-CoV-2 spike protein (RBD) and human ACE-2 receptor.

The novel coronavirus SARS-CoV-2 resulted in a significant worldwide health emergency known as the COVID-19 pandemic. This crisis has been marked by the widespread of various variants, with certain ones causing notable apprehension. In this study, we harnessed computational techniques to scrutinize these Variants of Concern (VOCs), including various Omicron subvariants. Our approach involved the use of protein structure prediction algorithms and molecular docking techniques, we have investigated the effects of mutations within the Receptor Binding Domain (RBD) of SARS-CoV-2 and how these mutations influence its interactions with the human angiotensin-converting enzyme 2 (hACE-2) receptor. Further we have predicted the structural alterations in the RBD of naturally occurring SARS-CoV-2 variants using the tr-Rosetta algorithm. Subsequent docking and binding analysis employing HADDOCK and PRODIGY illuminated crucial interactions occurring at the Receptor-Binding Motif (RBM). Our findings revealed a hierarchy of increased binding affinity between the human ACE2 receptor and the various RBDs, in the order of wild type (Wuhan-strain) < Beta < Alpha < Gamma < Omicron-B.1.1.529 < Delta < Omicron-BA.2.12.1 < Omicron-BA.5.2.1 < Omicron-BA.1.1. Notably, Omicron-BA.1.1 demonstrated the highest binding affinity of -17.4 kcal mol-1 to the hACE2 receptor when compared to all the mutant complexes. Additionally, our examination indicated that mutations occurring in active residues of the Receptor Binding Domain (RBD) consistently improved the binding affinity and intermolecular interactions in all mutant complexes. Analysis of the differences among variants has laid a foundation for the structure-based drug design targeting the RBD region of SARS-CoV-2.

Generation Mean Analysis Reveals the Predominant Gene Effects for Grain Iron and Zinc Contents in Pearl Millet.

Pearl millet [Pennisetum glaucum (L.) R. Br.] is a climate-resilient dryland cereal that has been identified as a potential staple food crop that can contribute to alleviating micronutrient malnutrition, particularly with respect to grain iron (Fe) and zinc (Zn) contents, in Sub-Saharan Africa and India. In this regard, an understanding of the inheritance pattern of genes involved in Fe and Zn contents is vital for devising appropriate breeding methods to genetically enhance their levels in grains. In this study, we aimed to determine the genetic effects underlying such inheritance and their interactions based on the generation mean analyses. Four experimental crosses and their six generations (P1, P2, F1, BCP1, BCP2, and F2) were independently evaluated in a compact family block design in 2017 rainy and 2018 summer seasons. ANOVA revealed highly significant mean squares (p < 0.01) among different generations for grain Fe and Zn contents. Six-parameter generation mean analyses revealed a predominance of additive genetic effect and a significant (p < 0.05) additive × dominant interaction for the grain Fe content. The additive genetic effect for the grain Zn content was also highly significant (p < 0.01). However, interaction effects contributed minimally with respect to most of the crosses for the grain Zn content and hence we assume that a simple digenic inheritance pattern holds true for it. Furthermore, we established that narrow-sense heritability was high for the grain Fe content (>61.78%), whereas it was low to moderate for the grain Zn content (30.60-59.04%). The lack of superior parent heterosis coupled with non-significant inbreeding depression for Fe and Zn contents in grains further confirmed the predominance of an additive genetic effect. These findings will contribute to strategizing a comprehensive breeding method to exploit the available variability of grain Fe and Zn contents for the development of biofortified hybrids of pearl millet.

Vitamin D status and bone mineral density in women of reproductive and postmenopausal age groups: a cross-sectional study from south India.

INTRODUCTION: This study documents 25(OH)D status and bone mineral density (BMD) in women of reproductive (WR) and post-menopausal (PMW) age-groups in south India. SUBJECTS AND METHODS: Serum calcium (Ca), phosphorus (iP), albumin, alkaline phosphatase (ALP), creatinine, 25(OH)D and intact parathormone (N-tact PTH) of WR (n = 55) and PMW (n = 136) women were analyzed over a period of one year. Bone mineral Density (BMD) (Hologic, USA) was estimated using Caucasian data as reference. RESULTS: In both, WR and in PMW 25(OH)D deficiency (< 20 ng/ml), insufficiency (20-30 ng/ml) and replete states (> 30 ng/ml) were seen in 76%, 16.5%, 7.5% vs 70%, 23% and 7% respectively. PMW had lower BMD (gm/cm2) than WR at forearm ( P = < 0.001), hip trochanter (P = < 0.0001), lumbar spine antero-posterior (LSAP) (P = < 0.001) and lateral (LS Lateral) (P = < 0.001). Osteoporosis was seen at hip (15% and 28%), forearm (nil and 11%), LSAP (6% and 22%) and LS lateral (0% and 23%) among WR and PMW respectively. BMD did not correlate with any of the biochemical indices but correlated with BMD at other sites. CONCLUSIONS: Vitamin D deficiency coexists with low BMD in our study group. Serum 25(OH)D needs to be documented in women having low BMD. Calcium and vitamin D need to be supplemented as part of therapy in PMW.