Identification of medicinal plant-based phytochemicals as a potential inhibitor for SARS-CoV-2 main protease (Mpro) using molecular docking and deep learning methods.

Highly transmissive and rapidly evolving Coronavirus disease-2019 (COVID-19), a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic, which is one of the most researched viruses in the academia. Effective drugs to treat people with COVID-19 have yet to be developed to reduce mortality and transmission. Studies on the SARS-CoV-2 virus identified that its main protease (Mpro) might be a potential therapeutic target for drug development, as this enzyme plays a key role in viral replication. In search of potential inhibitors of Mpro, we developed a phytochemical library consisting of 2431 phytochemicals from 104 Korean medicinal plants that exhibited medicinal and antioxidant properties. The library was screened by molecular docking, followed by revalidation by re-screening with a deep learning method. Recurrent Neural Networks (RNN) computing system was used to develop an inhibitory predictive model using SARS coronavirus Mpro dataset. It was deployed to screen the top 12 compounds based on their docked binding affinity that ranged from -8.0 to -8.9 kcal/mol. The top two lead compounds, Catechin gallate and Quercetin 3-O-malonylglucoside, were selected depending on inhibitory potency against Mpro. Interactions with the target protein active sites, including His41, Met49, Cys145, Met165, and Thr190 were also examined. Molecular dynamics simulation was performed to analyze root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (RG), solvent accessible surface area (SASA), and number of hydrogen bonds. Results confirmed the inflexible nature of the docked complexes. Absorption, distribution, metabolism, excretion, and toxicity (ADMET), as well as bioactivity prediction confirmed the pharmaceutical activities of the lead compound. Findings of this research might help scientists to optimize compatible drugs for the treatment of COVID-19 patients.

How air quality and COVID-19 transmission change under different lockdown scenarios? A case from Dhaka city, Bangladesh.

The transmission of novel coronavirus (COVID-19) can be reduced by implementing a lockdown policy, which has also been proven as an effective control measure for air pollution in the urban cities. In this study, we applied ground- and satellite-based data of five criteria air pollutants (PM2.5, NO2, SO2, O3, and CO) and meteorological factors from March 8 to May 15, 2020 (before, partial-, and full-lockdown). The generalized additive models (GAMs), wavelet coherence, and random forest (RF) model were employed to explore the relationship between air quality indicators and COVID-19 transmission in Dhaka city. Results show that overall, 26, 20.4, 17.5, 9.7 and 8.8% declined in PM 2.5, NO2, SO2, O3, and CO concentrations, respectively, in Dhaka City during the partial and full lockdown compared to the period before the lockdown. The implementation of lockdown policy for containing COVID-19 transmission played a crucial role in reducing air pollution. The findings of wavelet coherence and partial wavelet coherence demonstrate no standalone coherence, but interestingly, multiple wavelet coherence indicated a strong short-term coherence among air pollutants and meteorological factors with the COVID-19 outbreak. Outcomes of GAMs indicated that an increase of 1-unit in long-term exposure to O3 and CO (lag1) was associated with a 2.9% (95% CI: -0.3%, -5.6%), and 53.9% (95% CI: 0.2%, -107.9%) decreased risk of COVID-19 infection rate during the full-lockdown period. Whereas, COVID-19 infection and MT (mean temperature) are modulated by a peak during full-lockdown, which is mostly attributed to contact transmission in Dhaka city. RF model revealed among the parameters being studied, MT, RH (relative humidity), and O3 were the dominant factors that could be associated with COVID-19 cases during the study period. The outcomes reported here could elucidate the effectiveness of lockdown scenarios for COVID-19 containment and air pollution control in Dhaka city.