SARS-CoV-2 variants and spike mutations involved in second wave of COVID-19 pandemic in India.

Against the backdrop of the second wave of COVID-19 pandemic in India that started in March 2021, we have monitored the spike (S) protein mutations in all the reported (GISAID portal) whole-genome sequences of SARS-CoV-2 circulating in India from 1 January 2021 to 31 August 2021. In the 43,102 SARS-CoV-2 genomic sequences analysed, we have identified 24,260 amino acid mutations in the S protein, based on which 265 Pango lineages could be categorized. The dominant lineage in most of the 28 states of India and its 8 union territories was B.1.617.2 (the delta variant). However, the states Madhya Pradesh, Jammu & Kashmir, and Punjab had B.1.1.7 (alpha variant) as the major lineage, while the Himachal Pradesh state reported B.1.36 as the dominating lineage. A detailed analysis of various domains of S protein was carried out for detecting mutations having a prevalence of >1%; 70, 18, 7, 3, 9, 4, and 1 (N = 112) such mutations were observed in the N-terminal domain, receptor binding domain, C -terminal domain, fusion peptide region, heptapeptide repeat (HR)-1 domains, signal peptide domain, and transmembrane region, respectively. However, no mutations were recorded in the HR-2 and cytoplasmic domains of the S protein. Interestingly, 13.39% (N = 15) of these mutations were reported to increase the infectivity and pathogenicity of the virus; 2% (N = 3) were known to be vaccine breakthrough mutations, and 0.89% (N = 1) were known to escape neutralizing antibodies. The biological significance of 82% (N = 92) of the reported mutations is yet unknown. As SARS-CoV-2 variants are emerging rapidly, it is critical to continuously monitor local viral mutations to understand national trends of virus circulation. This can tremendously help in designing better preventive regimens in the country, and avoid vaccine breakthrough infections.

An in silico approach to study the interaction of BHA with selected steroid hormone receptors and investigating it's agonistic and antagonistic properties.

Antioxidant food additives were routinely used for increasing the keeping quality of packaged food items. Butylated Hydroxyanisole (BHA) is one of the most widely used synthetic phenolic antioxidants of such kind. Although quantity of antioxidants in packaged eatables and admissible daily intake (ADI) per person per day are limited by laws, the urbanisation and changes in lifestyle has cross these limits. Although studies on BHA has been carried out, there exists a great deal of uncertainty about the exact molecular mechanism of interaction of BHA with various receptors in the body. Since earlier reports suggested BHA plausibly interferes with reproductive system development, we opted docking of critical receptors of endogenous hormones controlling growth and development of reproductive system with BHA. Nuclear receptors of estrogen (ER), androgen (AR) and progesterone (PR) were selected for this purpose. This manuscript describes the comparison of binding pattern of BHA towards AR, ER and PR along with their agonists and antagonist. Lamarckian Genetic Algorithm of AutoDock 4.0 was used for analysing the mode of binding of ligands with the receptors. It is evident form the docking studies that, BHA exhibited similar binding pattern` with antagonists of AR and agonists of ER. But the interaction of BHA with PR was not compatible with either agonists or antagonists. The docking patterns produced could reliably demonstrate the interactions of BHA with selected receptors and also predict its possible agonistic and antagonistic action.