ABSTRACT
BACKGROUND: In November 2021, variant B.1.1.529 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified by the World Health Organization (WHO) and designated Omicron. Omicron is characterized by a high number of mutations, thirty-two in total, making it more transmissible than the original virus. More than half of those mutations were found in the receptor-binding domain (RBD) that directly interacts with human angiotensin-converting enzyme 2 (ACE2). This study aimed to discover potent drugs against Omicron, which were previously repurposed for coronavirus disease 2019 (COVID-19). All repurposed anti-COVID-19 drugs were compiled from previous studies and tested against the RBD of SARS-CoV-2 Omicron. METHODS: As a preliminary step, a molecular docking study was performed to investigate the potency of seventy-one compounds from four classes of inhibitors. The molecular characteristics of the best-performing five compounds were predicted by estimating the drug-likeness and drug score. Molecular dynamics simulations (MD) over 100 ns were performed to inspect the relative stability of the best compound within the Omicron receptor-binding site. RESULTS: The current findings point out the crucial roles of Q493R, G496S, Q498R, N501Y, and Y505H in the RBD region of SARS-CoV-2 Omicron. Raltegravir, hesperidin, pyronaridine, and difloxacin achieved the highest drug scores compared with the other compounds in the four classes, with values of 81%, 57%, 18%, and 71%, respectively. The calculated results showed that raltegravir and hesperidin had high binding affinities and stabilities to Omicron with ΔGbinding of - 75.7304 ± 0.98324 and - 42.693536 ± 0.979056 kJ/mol, respectively. Further clinical studies should be performed for the two best compounds from this study.
Subject(s)
COVID-19 , Hesperidin , Humans , Drug Repositioning , Molecular Docking Simulation , Raltegravir Potassium , SARS-CoV-2 , Molecular Dynamics Simulation , Protein BindingABSTRACT
Background: Health care providers (HCPs) have always been a common target of stigmatization during widespread infections and COVID-19 is not an exception. Aim: This study aims to investigate the prevalence of stigmatization during the COVID-19 pandemic among HCPs in seven different countries using the Stigma COVID-19 Healthcare Providers tool (S19-HCPs). Design: Cross-sectional. Methods: The S19-HCPs is a self-administered online survey (16-item) developed and validated by the research team. The participants were invited to complete an online survey. Data collection started from June-July 2020 using a convenience sample of HCPs from Iraq, Jordan, Egypt, Saudi Arabia, Indonesia, Philippines, and Kuwait. Results: A total number of 1726 participants were included in the final analysis. The majority of the study participants were Jordanians (22%), followed by Kuwaitis (19%), Filipinos (18%) and the lowest participants were Indonesians (6%). Other nationalities were Iraqis, Saudis, and Egyptians with 15%, 11% and 9% respectively. Among the respondents, 57% have worked either in a COVID-19 designated facility or in a quarantine center and 78% claimed that they had received training for COVID-19. Statistical significance between COVID-19 stigma and demographic variables were found in all aspect of the S19-HCPs. Conclusion: The findings of this study demonstrated high levels of stigmatization against HCPs in all the included seven countries. On the other hand, they are still perceived positively by their communities and in their utmost, highly motivated to care for COVID-19 patients. Educational and awareness programs could have a crucial role in the solution of stigmatization problems over the world.