ABSTRACT
SARS-CoV-2 enters the host cell through the ACE2 receptor and replicates its genome using an RNA-Dependent RNA Polymerase (RDRP). The functional RDRP is released from pro-protein pp1ab by the proteolytic activity of Main protease (Mpro) which is encoded within the viral genome. Due to its vital role in proteolysis of viral polyprotein chains, it has become an attractive potential drug target. We employed a hierarchical virtual screening approach to identify small synthetic protease inhibitors. Statistically optimized molecular shape and color-based features (various functional groups) from co-crystal ligands were used to screen different databases through various scoring schemes. Then, the electrostatic complementarity of screened compounds was matched with the most active molecule to further reduce the hit molecules' size. Finally, five hundred eighty-seven molecules were docked in Mpro catalytic binding site, out of which 29 common best hits were selected based on Glide and FRED scores. Five best-fitting compounds in complex with Mpro were subjected to MD simulations to analyze their structural stability and binding affinities with Mpro using MM/GB(PB)SA models. Modeling results suggest that identified hits can act as the lead compounds for designing better active Mpro inhibitors to enhance the chemical space to combat COVID-19.Communicated by Ramaswamy H. Sarma.
ABSTRACT
OBJECTIVE: Hospital sanitary workers are among the prime source to disseminate information at a massive level, however they received least attention during the pandemic COVID-19. The study was designed to investigate the prevailing myths and misconceptions of the coronavirus pandemic among the sanitary workers of health care system. Further, a systematic training program is devised and tested to demystify the false myths with discerning truth and awareness-raising in hospital sanitary workers. METHOD: A pre-post face-to-face intervention design was opted and the intervention was conducted at five locations by the project team. The intervention consisted a 3 days training program to target myths and misconceptions of hospital sanitary workers. The study was completed in 8 months starting from August, 2019 to March, 2020. Participants were recruited from local hospitals having a specialized indoor COVID treatment facility. The sample consisted of 82 participants (n = 25, 30.09% females) with age ranging from 18 to 60 years (M ± SD = 37.41 ± 10.09). FINDINGS: The results indicated that 86.4% of the participants never heard the name of the coronavirus before the pandemic in Pakistan. A majority of the participants (> 50%) believed on a very alarming but unrealistic rate of mortality i.e., 30-60%. The pre-testing showed a high prevalence of myths in all four domains (i.e., popular treatments = 24.44, conspiracy myths = 7.93, home remedies = 16.46, and COVID-reliance = 7.82). The pre and post comparison of individual myths showed significant improvement on 24 of the 26 myths with a decline ranging from 0.18 to 1.63. Overall, the intervention significantly decreased scores on all four domains of coronavirus myths. CONCLUSION: The training intervention appeared to effectively reduce myths and misconceptions of sanitary staff workers and is advised to be included as a standard training program for sanitary workers of health care system.