ABSTRACT
With the advent of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak, efforts are still in progress to find out a functional cure for the infection. Among the various protein targets, nsp16 capping protein is one of the vital targets for drug development as it protects the virus against the host cell nucleases and evading innate immunity. The nsp16 protein forms a heterodimer with a co-factor nsp10 and triggers 2'-O-methyltransferase activity which catalyzes the conversion of S-adenosyl methionine into S-adenosyl homocysteine. The free methyl group is transferred to the 2'-O position on ribose sugar at the 5' end of mRNA to form the cap-1 structure which is essential for replication of the virus and evading the innate immunity of the host. In this study, we identify a potential lead natural bioactive compound against nsp16 protein by systematic cheminformatic analysis of more than 144k natural compounds. Virtual screening, molecular docking interactions, ADMET profiling, molecular dynamics (MD) simulations, molecular mechanics-generalized born surface area (MM-GBSA), free energy analysis and density functional theory analysis were used to discover the potential lead compound. Our investigation revealed that ZINC8952607 (methyl-[(6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-yl)aminomethyl]BLAHone) has the greatest binding affinity and best pharmacokinetic parameters due to presence of carbazol and BLAHone (biaryl moiety). Further, time-dependent MD simulation analysis substantiates the stability and rigidness of nsp16 protein even after interaction with the lead compound. We believe that the compound ZINC8952607 might establish as a novel natural drug candidate against CoVID-19 infection.Communicated by Ramaswamy H. Sarma.
ABSTRACT
Deterioration of ambient air quality associated with urbanisation is a serious concern in many parts of the world. In India, air pollution, primarily due to particulate matter, has increased exponentially in the last few decades due to rapid urbanization, industrialization and population growth. This study investigates the non-uniform influence of COVID-19 lockdown on the ambient air quality of three distinct local climate zones (LCZs) within the urban region of Kochi (Kerala, India). The analysis of the air pollutant data of the ambient air quality monitoring stations during the pre-lockdown (PRLD), lockdown (LD) and post-lockdown (PTLD) periods of 2021 implies the significance of lockdown measures in the improvement of urban air quality. The air quality index (AQI) exhibits characteristic variability in different LCZs and contrasting behaviour between the LD period of 2020 and 2021, primarily due to the differences in the lockdown restrictions and strategies as well as the influence of local climatic factors. This study highlights the need for multiple monitoring stations in the urban regions with respect to different LCZs to identify the urban air quality hot spots.
ABSTRACT
This study assesses the effect of lockdown, due to the coronavirus disease (COVID-19) pandemic, on the concentration of different air pollutants and overall air quality of a less industrialized region (Kerala) of India. We analysed data from four ambient air quality stations over three years (January to May, 2018-2020) with pairwise comparisons, trend analysis, etc. Results indicated unprecedented reduction in the concentration of the air pollutants: nitrogen dioxide, NO2 (-48%), oxides of nitrogen, NOx (-53% to -90%), carbon monoxide, CO (-24% to -67%) and the particulate matter (-24% to -47% for particulate matter with a diameter of less than 2.5 μm, PM2.5;-17% to -20% for particulate matter with a diameter of less than 10 μm, PM10), as well as the reduction of the National Air Quality Index (NAQI). These reductions indicate an overall improvement of the ambient air quality due to restrictions on transportation, construction, and the industrial sectors during lockdown, even in an area considered less industrial. Despite the general decreasing trend of the concentration of various air pollutants from January to May, suggesting seasonal influences, the trend was intensified in the year 2020 due to the added effect of the lockdown measures. Comparison of results with those from larger and more industrialized cities suggests that the effects of lockdown are more variable, and focused on the levels of gaseous pollutants. Findings from this study demonstrate the far-reaching effects and implications of the COVID-19 lockdown on ambient air quality, even on less industrialized and less urbanized regions.