RESUMO
SARS-CoV-2 triggered a worldwide medical crisis, affecting the world's social, emotional, physical, and economic equilibrium. However, treatment choices and targets for finding a solution to COVID-19's threat are becoming limited. A viable approach to combating the threat of COVID-19 is by unraveling newer pharmacological and therapeutic targets pertinent in the viral survival and adaptive mechanisms within the host biological milieu which in turn provides the opportunity to discover promising inhibitors against COVID-19. Therefore, using high-throughput virtual screening, manually curated compounds library from some medicinal plants were screened against four main drivers of SARS-CoV-2 (spike glycoprotein, PLpro, 3CLpro, and RdRp). In addition, molecular docking, Prime MM/GBSA (molecular mechanics/generalized Born surface area) analysis, molecular dynamics (MD) simulation, and drug-likeness screening were performed to identify potential phytodrugs candidates for COVID-19 treatment. In support of these approaches, we used a series of computational modeling approaches to develop therapeutic agents against COVID-19. Out of the screened compounds against the selected SARS-CoV-2 therapeutic targets, only compounds with no violations of Lipinski's rule of five and high binding affinity were considered as potential anti-COVID-19 drugs. However, lonchocarpol A, diplacol, and broussonol E (lead compounds) were recorded as the best compounds that satisfied this requirement, and they demonstrated their highest binding affinity against 3CLpro. Therefore, the 3CLpro target and the three lead compounds were selected for further analysis. Through protein-ligand mapping and interaction profiling, the three lead compounds formed essential interactions such as hydrogen bonds and hydrophobic interactions with amino acid residues at the binding pocket of 3CLpro. The key amino acid residues at the 3CLpro active site participating in the hydrophobic and polar inter/intra molecular interaction were TYR54, PRO52, CYS44, MET49, MET165, CYS145, HIS41, THR26, THR25, GLN189, and THR190. The compounds demonstrated stable protein-ligand complexes in the active site of the target (3CLpro) over a 100 ns simulation period with stable protein-ligand trajectories. Drug-likeness screening shows that the compounds are druggable molecules, and the toxicity descriptors established that the compounds demonstrated a good biosafety profile. Furthermore, the compounds were chemically reactive with promising molecular electron potential properties. Collectively, we propose that the discovered lead compounds may open the way for establishing phytodrugs to manage COVID-19 pandemics and new chemical libraries to prevent COVID-19 entry into the host based on the findings of this computational investigation.
RESUMO
The microbial quality of two groundwater sources (well and borehole) and associated risks were quantitatively assessed. Water samples from the selected borehole and well were collected over a period of 12 weeks (n = 48). The concentrations of Escherichia coli, faecal coliforms, Salmonella, Shigella, Clostridium, Bifidobacterium and Campylobacter were determined using standard microbiological methods, which involve the use of a membrane filter technique. The water samples were filtered through a 0.45 µm membrane filter using vacuum pump pressure and plated on selective agar for the bacteria under test. The number of colonies of the bacterial growth observed after the incubation period was counted and recorded. The physicochemical properties of the water were determined using standard methods. The risk of Salmonella, Shigella, Clostridium and Campylobacter infections resulting from the ingestion of water from the borehole and well was estimated. The results showed that the levels of enteric bacteria in the borehole were higher than those in the well. The mean levels of E. coli in water from the borehole and well were 3.3 and 1.7 log10 cfu/100 ml, respectively, and exhibited a negative relationship with salinity (r = -0.53). The estimated risks of infection associated with the pathogens in water from the borehole and well were greater than the acceptable risk limit of 10-4 and followed this order Clostridium < Salmonella < Campylobacter < Shigella. The findings of this study suggest recent and continuous faecal contamination of the two groundwater sources, thus exposing the residents relying on the water for drinking to potential risks of gastrointestinal infections.
