The SARS-CoV-2 main protease, a vital enzyme for virus replication, is a potential target for developing drugs in COVID-19 treatment. Until now, three SARS-CoV-2 main protease inhibitors have been approved for COVID-19 treatment. This study explored the inhibitory potency of asymmetric imidazole-4,5-dicarboxamide derivatives against the SARS-CoV-2 main protease. Fourteen derivatives were designed based on the structure of the SARS-CoV-2 main protease active site, the hydrolysis mechanism, and the experience gained from the reported inhibitor structures. They were synthesized through a four-step procedure from benzimidazole and 2-methylbenzimidazole. SARS-CoV-2 main protease inhibition was evaluated by fluorogenic assay with lopinavir, ritonavir, and ebselen as positive references. -(4-Chlorophenyl)-2-methyl-4-(morpholine-4-carbonyl)-1-imidazole-5-carboxamide (5a2) exhibited the highest potency against the SARS-CoV-2 main protease with an IC of 4.79 ± 1.37 μM relative to ebselen with an IC of 0.04 ± 0.013 μM. Enzyme kinetic and molecular docking studies were carried out to clarify the inhibitory mechanism and to prove that the compound interacts at the active site. We also performed cytotoxicity assay to confirm that these compounds are not toxic to human cells.
Objective: The COVID-19 pandemic highlighted and exacerbated health inequities worldwide. While several studies have examined the impact of individual social factors on COVID infection, our objective was to examine how interactions of social factors were associated with the risk of testing positive for SARS-CoV-2 during the first two years of the pandemic.
Study Design And Setting: We conducted an observational cohort study using linked health administrative data for Ontarians tested for SARS-CoV-2 between January 1st, 2020, and December 31st, 2021.
Cardiovascular involvements are one of the most important and threatening problems of SARS-CoV-2 infection and can cause a wide range of clinical manifestations in children. Therefore, a review of previous studies is necessary to prevent the occurrence of cardiovascular complications and reduce the risk of mortality in this age group of patients. To investigate the cardiovascular complications in children with COVID-19, international authoritative databases including PubMed, Scopus, Embase, Web of Science, Google Scholar, and Persian databases were searched using the main concepts, all articles were published between January 2020 and November 2022.
Background: We have previously developed and reported on a procedure for estimating the purported benefits of immunity mandates using a novel variant of the number needed to treat (NNT) which we called the number needed to isolate (NNI). Here we demonstrate its broader properties as a useful population health metric.
Main Body: The NNI is analogous to the number needed to treat (NNT = 1/ARR), except the absolute risk reduction (ARR) is the absolute transmission risk in a specific population.
Introduction: The COVID-19 pandemic has taught myriad lessons and left several questions we are yet to comprehend. Initially, the scientific community was concerned with the management of acute disease and immunization. Once the peak of the pandemic receded, it became clear that a proportion of patients were far from fully recovered.
Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.
