ABSTRACT
A novel series of bis- (Abdelhamid et al., 2017, Banerjee et al., 2018, Bharanidharan et al., 2022)thiadiazoles was synthesized from the reaction of precursor dimethyl 2,2'-(1,2-diphenylethane-1,2-diylidene)-bis(hydrazine-1-carbodithioate) and hydrazonyl chlorides in ethanol under ultrasonic irradiation. Spectral tools (IR. NMR, MS, elemental analyses, molecular dynamic simulation, DFT and LUMO and HOMO) were used to elucidate the structure of the isolated products. Molecular docking for the precursor, 3 and ligands 6a-i to two COVID-19 important proteins Mpro and RdRp was compared with two approved drugs, Remdesivir and Ivermectin. The binding affinity varied between the ligands and the drugs. The highest recorded binding affinity of 6c with Mpro was (-9.2 kcal/mol), followed by 6b and 6a, (-8.9 and -8.5 kcal/mol), respectively. The lowest recorded binding affinity was (-7.0 kcal/mol) for 6 g. In comparison, the approved drugs showed binding affinity (-7.4 and -7.7 kcal/mol), for Remdesivir and Ivermectin, respectively, which are within the range of the binding affinity of our ligands. The binding affinity of the approved drug Ivermectin against RdRp recoded the highest (-8.6 kcal/mol), followed by 6a, 6 h, and 6i are the same have (-8.2 kcal/mol). The lowest reading was found for compound 3 ligand (-6.3 kcal/mol). On the other side, the amino acids also differed between the compounds studied in this project for both the viral proteins. The ligand 6a forms three H-bonds with Thr 319(A), Sr 255(A) and Arg 457(A), whereas Ivermectin forms three H-bonds with His 41(A), Gly143(A) and Gln 18(A) for viral Mpro. The RdRp amino acids residues could be divided into four groups based on the amino acids that interact with hydrogen or hydrophobic interactions. The first group contained 6d, 6b, 6 g, and Remdesivir with 1-4 hydrogen bonds and hydrophobic interactions 1 to 10. Group 2 is 6a and 6f exhibited 1 and 3 hydrogen bonds and 15 and 14 hydrophobic interactions. Group 3 has 6e and Ivermectin shows 4 and 3 hydrogen bonds, respectively and 11 hydrophobic interactions for both compounds. The last group contains ligands 3, 6c, 6 h, and 6i gave 1-3 hydrogen bonds and 6c and 3 recorded the highest number of hydrophobic interactions, 14 for both 6c and 6 h. Pro Tox-II estimated compounds' activities as Hepatoxic, Carcinogenic and Mutagenic, revealing that 6f-h were inactive in all five similar to that found with Remdesivir and Ivermectin. The drug-likeness prediction was carried out by studying physicochemical properties, lipophilicity, size, polarity, insolubility, unsaturation, and flexibility. Generally, some properties of the ligands were comparable to that of the standards used in this study, Remdesivir and Ivermectin.
ABSTRACT
BACKGROUND: Due to the authorization to do outdoor sports in Algeria, the government allowed the sports that do not require physical contact. The purpose of this study is to show the benefits of 06 weeks of high interval intensity training (HIIT) based on body weight movement and sprint on developing maximum oxygen consumption (VO2max), power, maximum aerobic speed (VMA), endurance, and losing weight during the pandemic of covid-19. METHODS: 11 persons participate in this study belonging to the fitness club in Bordj Bou Arreridj – Algeria – (age: 32.18± 8.08 year, high: 1.78 ± 0.052 cm, weight: 84.24 ± 11.25 kg, BMI: 26.50± 3.95 kg). the protocol was contained 3 session moderate intensity, pretest, 6weeks HIIT 3 sessions per week, and ensure that the heart rate is 100% during the exercise finally, post-tests. RESULTS: similar increases (p < 0.05) in distance of running by (226,54m, 17.30%). And VMA it enhanced by 2.26 km/h with 17.34%. While VO2max it’s developed by 17.28% (7.92 mL/kg/min). with very large effect size (ES=1.75). In addition, the power of legs it boosted by 3.17% (6.27 cm) with small effect size (0.58). Also, results indicate decrease in weight by 2.73 with large effect size (0.87). CONCLUSION: the outdoor exercise it seems safe to do during the pandemic of covid-19. Results highlight great effect of HIIT on enhancing (VO2max, power, VMA, endurance, and losing weight). © 2022 English Language and Literature Association of Korea. All rights reserved.