Safety of COVID-19 vaccines.

This study is aimed to identify the adverse effects associated with three types of coronavirus disease 2019 vaccines. Approximately 1736 individuals agreed to participate in this study. The participants involved in the study were individuals who had received the first dose or full course (two doses) of the vaccine at least 30 days before the survey. A direct and interactive web-based system interview with a paper and electronic version of the questionnaire was used for all participants. A total of 1736 randomized individuals were identified. The reactogenicity of the vaccines including pain, redness, urticaria, and swelling at the site of the injection was reported in 34.56% of the participants. Local site reaction was reported in more individuals who had Pfizer and AstraZeneca vaccines than those who received the Sinopharm vaccine. The systemic events were more common with AstraZeneca and Pfizer vaccines, symptoms reported were fatigue, body pain, headache, muscle pain, fever, and gastrointestinal side effects. There were no correlations between age or gender, and the duration of the adverse effects for the three vaccines. Swelling and severe allergic reaction of the eyelids, severe hypotension, generalized body aches, shortness of breath, weakness and numbness on the injected arm, acute hyperglycemia, severe chest pain, and fever more than 39°C were among the unusual signs and symptoms reported by the participants. Pfizer, AstraZeneca, and Sinopharm vaccines were found to be safe and Sinopharm vaccine showed a lower prevalence of adverse effects compared with the other vaccines. The duration and severity of adverse effects were not affected by age or gender. Unusual side effects should be closely monitored to establish determine they are linked to the immunization.

Anticancer Activity and In Silico ADMET Properties of 2,4,5-Trisubstitutedthiazole Derivatives.

BACKGROUND: Recently, a series of 15 compounds with 2,4,5-trisubstitutedthiazole scaffold having 2- amino/amido/ureido functional groups attached with 5-aryl and 4-carboxylic acid/ester groups (1-15) were reported from our research group as novel potential inhibitors of carbonic anhydrase III (CA III) enzyme. Several research studies revealed the potential role of CA inhibitors as anticancer agents, giving us the impetus to further explore these compounds for their potential as anticancer agents. OBJECTIVES: The objective of this study is to investigate the potential of 2,4,5-trisubstitutedthiazole derivatives (1-15) for their possible cytotoxic activity (in vitro), and to calculate (in silico) the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties to evaluate the drug-likeness of these compounds. METHODS: Cytotoxic activity (in vitro) was carried out on two breast cancer cell lines (MCF7 and MDA231), and the lymphoblastoid human erythroleukemia cell line (K562) using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Doxorubicin was used as a positive control. ADMET properties were calculated (in silico) using the QikProp module of Schrodinger. RESULTS: Compounds 6 and 9 with a phenylureido group at 2-position, and a methyl-carboxylate moiety at 4-position having para-tolyl and benzyl moiety, respectively at the 5-position of the thiazole ring showed significant cytotoxicity against all the three cell lines. In particular, compound 6 with para-tolyl group at 5-position exhibited the most potent inhibitory effect on the viability of MCF7, MDA231 and K562 cells, with IC50 values of 22, 26 and 11 µM, respectively. Notably, all the highly active compounds possess a phenyluriedo group at 2-- position with a methyl ester group at 4-position, indicating the probable role of these substituents in the target interaction and inducing cytotoxicity. Interestingly, compounds 1-4 and 10-13 with a free amino group at 2-position did not show any cytotoxic effect on the K562 cell line, while exhibiting mild to moderate cytotoxicity against the MCF7 and MDA231 cell lines. However, none of the tested compounds showed any activity against normal human dermal fibroblast cells indicating the safety/tolerability of the examined concentrations. Furthermore, these compounds also exhibited satisfactory ADMET properties (in silico), without violating Lipinski's rule of five. CONCLUSION: The most active compounds 6 and 9 predicted to have good oral absorption and low human serum protein binding, exhibiting no reactive functional group and probable CNS activity compared with 95% of the known oral drugs as predicted (in silico) by QikProp. Thus, compounds 6 and 9 can be considered as lead molecules for further modification and discovery of novel anticancer agents with nanomolar potency.

Presenting the characteristics, smoking versus diabetes, and outcome among patients hospitalized with COVID-19.

METHODS: We designed a cross-sectional, observational follow-up for 284 COVID-19 patients involving healthy patients, smokers, diabetics, and diabetic plus smokers recruited from May 1, 2020 to June 25, 2020. The clinical features, severity, duration, and outcome of the disease were analyzed. RESULTS: Of 284 COVID-19 patients, the median age was 48 years (range, 18-80), and 33.80% were female. Common symptoms included fever (85.56%), shortness of breath (49.65%), cough (45.42%), and headache (40.86%). Patients with more than one comorbidity (diabetes and smoking) presented as severe-critical cases compared to healthy patients, diabetics, and smokers. Smokers presented with a lower rate of death in comparison to diabetic patients and diabetic + smoking, furthermore, smoking was less risky than diabetes. Although the mortality rate was high in patients with smokers compared to healthy patients (4.22%, the hazard ratio [HR], 1.358; 95% confidence interval [CI], 1.542-1.100; p = .014), it was less than in diabetics (7.04%, HR 1.531, 95% CI: 1.668-1.337, p = .000), and diabetic plus smoker (10.00%, HR, 1.659; 95% CI, 1.763-1.510; p = .000). CONCLUSION: Multiple comorbidities are closely related to the severity of COVID-19 disease progression and the higher mortality rate. Smokers presented as mild cases compared to diabetic and diabetic + smoking patients, who presented as severe to critical cases. Although a higher death rate in smokers was seen compared with healthy patients, this was smaller when compared to diabetic and diabetic + smoking patients.