RESUMO
Bioactive fractions or compounds obtained from medicinal plants have been used for the treatment of multiple diseases. This effect could be due to common pathways underlying these conditions that are targeted by such medicines. In this study, we explored the molecular basis of action of one such herbal formulation Cissampelos pareira, used for the treatment of female hormone disorders and fever. Genome-wide expression studies on MCF7 cell lines treated with Cipa extract were carried out using Affymetrix arrays. Transcriptome analysis revealed a downregulation of signatures of estrogen response governed by estrogen receptor (ER). Molecular docking analysis identified 38 constituent molecules in Cipa that potentially bind ({Delta}G< -7.5) with ER at the same site as estrogen. Cipa transcriptome signatures show high positive connectivity (https://clue.io/) scores with protein translation inhibitors such as emetine (score: 99.61) and knockdown signatures of genes linked to the antiviral response such as ribosomal protein RPL7 (score: 99.92), which is also an ER coactivator. Cipa exhibits antiviral activity in dengue infected MCF7 cells that is decreased upon ESR1 (estrogen receptor 1) gene knockdown. This approach reveals a novel pathway involving ESR1-RPL7 axis that could be a potential target in dengue viral infection.
RESUMO
To understand the spread of SARS-CoV2, in August and September 2020, the Council of Scientific and Industrial Research (India), conducted a sero-survey across its constituent laboratories and centers across India. Of 10,427 volunteers, 1058 (10.14%) tested positive for SARS CoV2 anti-nucleocapsid (anti-NC) antibodies; 95% with surrogate neutralization activity. Three-fourth recalled no symptoms. Repeat serology tests at 3 (n=346) and 6 (n=35) months confirmed stability of antibody response and neutralization potential. Local sero-positivity was higher in densely populated cities and was inversely correlated with a 30 day change in regional test positivity rates (TPR). Regional seropositivity above 10% was associated with declining TPR. Personal factors associated with higher odds of sero-positivity were high-exposure work (Odds Ratio, 95% CI, p value; 2{middle dot}23, 1{middle dot}92-2{middle dot}59, 6{middle dot}5E-26), use of public transport (1{middle dot}79, 1{middle dot}43-2{middle dot}24, 2{middle dot}8E-06), not smoking (1{middle dot}52, 1{middle dot}16-1{middle dot}99, 0{middle dot}02), non-vegetarian diet (1{middle dot}67, 1{middle dot}41-1{middle dot}99, 3{middle dot}0E-08), and B blood group (1{middle dot}36,1{middle dot}15-1{middle dot}61, 0{middle dot}001). Impact StatementWidespread asymptomatic and undetected SARS-CoV2 infection affected more than a 100 million Indians by September 2020. Declining new cases thereafter may be due to persisting humoral immunity amongst sub-communities with high exposure. FundingCouncil of Scientific and Industrial Research, India (CSIR)
