Sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA (ssRNA) virus, responsible for severe acute respiratory disease (COVID-19). A large number of natural compounds are under trial for screening compounds, possessing potential inhibitory effect against the viral infection. Keeping in view the importance of marine compounds in antiviral activity, we investigated the potency of some marine natural products to target SARS-CoV-2 main protease (M pro) (PDB ID 6MO3). The crystallographic structure of M pro in an apo form was retrieved from Protein Data Bank and marine compounds from PubChem. These structures were prepared for docking and the complex with good docking score was subjected to molecular dynamic (MD) simulations for a period of 100 ns. To measure the stability, flexibility, and average distance between the target and compounds, root mean square deviations (RMSD), root mean square fluctuation (RMSF), and the distance matrix were calculated. Among five marine compounds, C-1 (PubChem CID 11170714) exhibited good activity, interacting with the active site and surrounding residues, forming many hydrogen and hydrophobic interactions. The C-1 also attained a stable dynamic behavior, and the average distance between compound and target remains constant. In conclusion, marine natural compounds may be used as a potential inhibitor against SARS-CoV-2 for better management of COVID-19.

Graphical abstract

Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro), Journal of Biomolecular Structure and Dynamics,

Patch-clamp recordings indicated the presence of P2X7 receptors at neural progenitor cells (NPCs) in the subgranular zone of the dentate gyrus in hippocampal brain slices prepared from transgenic nestin reporter mice. The activation of these receptors caused inward current near the resting membrane potential of the NPCs, while P2Y1 receptor activation initiated outward current near the reversal potential of the P2X7 receptor current. Both receptors were identified by biophysical/pharmacological methods. When the brain slices were prepared from mice which underwent a pilocarpine-induced status epilepticus or when brain slices were incubated in pilocarpine-containing external medium, the sensitivity of P2X7 and P2Y1 receptors was invariably increased. Confocal microscopy confirmed the localization of P2X7 and P2Y1 receptor-immunopositivity at nestin-positive NPCs. A one-time status epilepticus in rats caused after a latency of about 5 days recurrent epileptic fits. The blockade of central P2X7 receptors increased the number of seizures and their severity. It is hypothesized that P2Y1 receptors after a status epilepticus may increase the ATP-induced proliferation/ectopic migration of NPCs; the P2X7 receptor-mediated necrosis/apoptosis might counteract these effects, which would otherwise lead to a chronic manifestation of recurrent epileptic fits.

ObjectivesTo explore the association of maternal education and empowerment with childhood polio vaccination using nationally representative data of Pakistani mothers in a reproductive age group.DesignCross-sectional.SettingSecondary analysis of Pakistan Demographic and Health Survey (PDHS), 2012–2013 data was performed.ParticipantsOf the 13 558 mothers included in the survey sample, 6982 mothers were able to provide information regarding polio vaccinations.Main outcome measuresPolio vaccination coverage among children aged up to 5 years was categorised as complete vaccination (all four oral polio vaccine (OPV) doses), incomplete vaccination, and no vaccination (zero OPV dose received). Mothers' empowerment status was assessed using standard ‘Measure DHS’ questions regarding their involvement in decision-making related to health, household possessions and visits among family and friends. Education was categorised as no education, primary, secondary and higher education. Results of multinomial regression analyses were reported as adjusted OR with 95% CI. We adjusted for age, wealth index, urban/rural residence, place of delivery, and antenatal and postnatal visits.ResultsOnly 56.4% (n=3936) of the children received complete polio vaccination. Women with no education had significantly higher odds of their child receiving no polio vaccination (OR 2.34, 95% CI 1.05 to 5.18; p<0.01) and incomplete vaccination (OR 1.40, 95% CI 1.04 to 1.87; p<0.01). Further, unempowered women also had significantly higher odds of not taking their child for any polio vaccination (OR 1.58, 95% CI 1.17 to 2.12; p<0.01) and incomplete vaccination (OR 1.18, 95% CI 1.00 to 1.41; p=0.04).ConclusionsIlliteracy, socioeconomic status and empowerment of women remained significant factors linked to poorer uptake of routine polio vaccination.