ABSTRACT
The COVID-19 pandemic has already taken many lives but is still continuing its spread and exerting jeopardizing effects. This study is aimed to find the most potent ligands from 703 analogs of remdesivir against RNA-dependent RNA polymerase (RdRp) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus . RdRp is a major part of a multi-subunit transcription complex of the virus, which is essential for viral replication. In clinical trials, it has been found that remdesivir is effective to inhibit viral replication in Ebola and in primary human lung cell cultures; it effectively impedes replication of a broad-spectrum pre-pandemic bat coronaviruses and epidemic human coronaviruses. After virtual screening, 30 most potent ligands and remdesivir were modified with triphosphate. Quantum mechanics-based quantitative structure-activity relationship envisages the binding energy for ligands applying partial least square (PLS) regression. PLS regression remarkably predicts the binding energy of the effective ligands with an accuracy of 80% compared to the value attained from molecular docking. Two ligands (L4:58059550 and L28:126719083), which have more interactions with the target protein than the other ligands including standard remdesivir triphosphate, were selected for further analysis. Molecular dynamics simulation is done to assess the stability and dynamic nature of the drug-protein complex. Binding-free energy results via PRODIGY server and molecular mechanics/Poisson-Boltzmann surface area method depict that the potential and solvation energies play a crucial role. Considering all computational analysis, we recommend the best remdesivir analogs can be utilized for efficacy test through in vitro and in vivo trials against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
ABSTRACT
BACKGROUND: There is a lack of research investigating the confluence of risk factors in urban slums that may make them accelerators for respiratory, droplet infections like COVID-19. Our working hypothesis was that, even within slums, an inverse relationship existed between living density and access to shared or private WASH facilities. METHODS: In an exploratory, secondary analysis of World Bank, cross-sectional microdata from slums in Bangladesh we investigated the relationship between intra-household population density (crowding) and access to private or shared water sources and toilet facilities. RESULTS: The analysis showed that most households were single-room dwellings (80.4%). Median crowding ranged from 0.55 m2 per person up to 67.7 m2 per person. The majority of the dwellings (83.3%), shared both toilet facilities and the source of water, and there was a significant positive relationship between crowding and the use of shared facilities. CONCLUSION: The findings highlight the practical constraints on implementing, in slums, the conventional COVID19 management approaches of social distancing, regular hand washing, and not sharing spaces. It has implications for the management of future respiratory epidemics.