ABSTRACT
Due to the length of time required to develop specific antiviral agents, the World Health Organization adopted the strategy of repurposing existing medications to treat Coronavirus disease 2019 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease is possible biological target for potential antiviral drugs. We selected various compounds from PubChem database based on the structure of main protease inhibitors in Protein Data Bank database. Ten compounds showed nontumorigenic and nonmutagenic potential and met Egan's and Lipinski's rules. Molecular docking analysis was performed using AutoDock Vina software. Based on number and type of key binding interactions, as well as docking scores, we selected compounds 6, 8, and 17 that demonstrated the highest binding affinity for the target protein. Molecular dynamics simulations were then carried out on the protein-top docked ligand complexes which were subjected to Molecular mechanics/generalized Born and surface area calculations. The molecular dynamics simulation results indicated that protein-top docked ligand complexes showed good conformational stability. Among analyzed molecules, compound 17 emerged as the best in silico hit based on the docking score, MM/GBSA binding energy and MD results.
ABSTRACT
Introduction: In setting of global pandemic of coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cases resembling Kawasaki disease (KD) were repeatedly reported. Soon afterwards it began to be considered as separate entity named multisystem inflammatory syndrome in children (MIS-C). In addition to this newly recognized syndrome which has overlapping features with KD and is still occasionally described as its from, during COVID-19, a high incidence of Kawasaki-like syndrome (KLS) with mild to moderate symptoms was also noted. Recently, it was proposed that even such cases should, in clinical context, be treated as MIS-C if appropriate criteria are met. On the other hand, clear distinction of the two entities can help researchers to answer the question of its etiology and pathogenesis and could direct the clinicians what to expect during the course of the disease. Objectives: The aim was to describe main epidemiologic and clinical characteristics of KLS during the first year of COVID-19 pandemic. Methods: This retrospective study included analysis of medical documentation of patients treated for KLS at Clinic of Pediatrics, University Clinical Center Niš, between March 2020 and 2021. Inclusion criteria was fulfillment of KD or KLS criteria, based on CDC1 or WHO2 recommendation. Severe form of the disease with signs of a shock was exclusion criteria. The results were elaborated with the statistical method of descriptive and quantitative analysis. Results: A total of 21 subjects fulfilled the criteria for KLS during the study period. The cumulative incidence was 8.48 per 105 minors. Male to female ratio was 2:1 and mean age at diagnosis was 6.5 years (min. 8 months;max. 17 years). In fourteen cases current or recent COVID-19 infection or confirmed COVID-19 exposure was observed. When only these patients are analyzed average age was 8.2 years. Antibodies against SARS-CoV-2 were confirmed in seven patients, three had positive PCR test for COVID-19 and one had close contact with someone who has COVID-19 but COVID-19 was not proved. Interestingly, three patients that were antigen positive had respiratory organ involvement. In the reaming seven cases all the other possible causes of symptoms were ruled out and possible contact with SARS-CoV-2 was assumed. In addition to prolonged fever, that was present in all patients, polymorphous rash (95%) was the most common clinical feature flowed by bilateral nonpurulent conjunctivitis (47%). Gastrointestinal tract involvement was the most common internal organ manifestation. Treatment included corticosteroids (15 patients), intravenous immunoglobulin (1 patient) and two patients received nonsteroidal anti-inflammatory drug in anti-inflammatory dose, while the rest were only treated symptomatically. Favorable outcome was achieved in all patients with no morphological changes observed on echocardiography during the hospitalization and 2 weeks after discharge. Conclusion: Our findings suggest connection between infection and occurrence of the disease in susceptible children. Yet, a large portion of the population had contact with SARS-CoV-2, thus the exact role of infectious agent and pathophysiological mechanisms have to be determined. Gender distribution with male dominance among our patients is expected. Still, average age at diagnosis was bit higher than what is usually observed in classic KD and is more in line with characteristics of MIS-C. Further research are to be done in order to define what determine progression of the disease and are there any signs that may point in which way it will develop. Only in that way the clinicians would made right choices regarding the patients treatment.
ABSTRACT
Current developments have contributed to organisations paying increasing attention to protecting resources, employee safety, and applying quality products and services. There is a need for increasing the application of standards that define the way of managing quality, safety at work, risk, and many others. One such organisation is the Serbian Army, a complex centralised system that requires integrating these standards, and often stricter, in all fields of its activities. The current situation in the world, and therefore in Serbia, is sufficient motivation for the project provided by this paper. This project aims to show the integration of risk management systems and occupational safety systems, through the level of protection and exposure of members of the army to the virus infection COVID-19 during the implementation of emergency tasks, by defining risks and proposing additional measures to reduce the level of risk and increase the protection of military personnel. © 2021 by the authors. It was submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).