Comparative inhibition analysis of wild type and G671S catalytic site mutant of the SARS-CoV-2 RNA-dependent RNA polymerase

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has wrecked a global havoc, after its emergence in Wuhan, Hubei province of China. It is known to have a distressing effect on the respiratory tract and has a high mortality rate. Till to date (25 Dec 2021), total number of cases (279,362,428) have been reported across the globe. Variable mutations have been reported on various geographical levels. In this study, we have analyzed G671S mutation of RdRp of the SARS-CoV-2, which has been reported in various strains globally, but importantly delta variant cases of Pakistan and has a serious impact on the protein structure. To study the conformational impact, we screened a Tibetan medicinal compound/Sowa Rigpa library against RdRp and compared the best docked compound (Kaempferol 3-O-gentiobioside) to the wild type and mutant RdRp against Remdesivir. A short simulation was used to validate the findings. Both remdesivir and our screened compound showed better inhibition for mutant, compared to the wild type RdRp.

Design of D-amino acids SARS-CoV-2 Main protease inhibitors using the cationic peptide from rattlesnake venom as a scaffold

The C30 Endopeptidase (3C-like protease; 3CLpro) is essential for the life cycle of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) since it plays a pivotal role in viral replication and transcription and is hence a promising drug target. Molecules isolated from animals, insects, plants or microorganisms can serve as a scaffold for the design of novel biopharmaceutical products. Crotamine, a small cationic peptide from the venom of the rattlesnake Crotalus durissus terrificus has been the focus of many studies since it exhibits activities such as analgesic, in vitro antibacterial and hemolytic activities. The crotamine derivative L-peptides (L-CDP) that inhibit the 3CL protease in the low μM range were examined since they are susceptible to proteolytic degradation; we explored the utility of their D-enantiomers form. Comparative uptake inhibition analysis showed D-CDP as a promising prototype for a D-peptide-based drug. We also found that the D-peptides can impair SARS-CoV-2 replication in vivo, probably targeting the viral protease 3CLpro.

Experimental Analysis Of Generic Antibiotics Along With Honey Sensitivity Against Microbial Flora Obtained From Frozen Hilsa Fish (Tenualosa ilisha)

This study deals with the in-vitro experimental analysis of different generic antibiotics and season based honey, sensitivity against isolated bacteria. The characterization of bacteria isolated from the frozen hilsa is done through various biochemical reactions The antibacterial sensitivity of honey and antibiotics are evaluated through zone of inhibition analysis of bacterial colony. So, it is obvious that this experiment provides providential values for future research including food value analysis.

Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model

Over 182 million confirmed cases of COVID-19 and more than 4 million deaths have been reported to date around the world. It is essential to identify broad-spectrum antiviral agents that may prevent or treat infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also by other coronaviruses that may jump the species barrier in the future. We evaluated the antiviral selectivity of griffithsin and sulfated and non-sulfated polysaccharides against SARS-CoV-1 and SARS-CoV-2 using a cytotoxicity assay and a cell-based pseudoviral model. The half-maximal cytotoxic concentration (CC50) and half-maximal effective concentration (EC50) were determined for each compound, using a dose-response-inhibition analysis on GraphPad Prism v9.0.2 software (San Diego, CA, USA). The therapeutic index (TI = CC50/EC50) was calculated for each compound. The potential synergistic, additive, or antagonistic effect of different compound combinations was determined by CalcuSyn v1 software (Biosoft, Cambridge, UK), which estimated the combination index (CI) values. Iota and lambda carrageenan showed the most potent antiviral activity (EC50 between 3.2 and 7.5 µg/mL). Carrageenan and griffithsin combinations exhibited synergistic activity (EC50 between 0.2 and 3.8 µg/mL; combination index <1), including against recent SARS-CoV-2 mutations. The griffithsin and carrageenan combination is a promising candidate to prevent or treat infections by SARS-CoV-1 and SARS-CoV-2.

The Influence of Music Training on Motoric Inhibition in German Preschool Children

The aim of our experiment was to investigate the effect of a music training program on motoric inhibition in German preschoolers. Studies have shown that in children, music lessons and inhibition are associated, and that music training might have the potential to improve inhibition. Improving executive functions is particularly useful in young children as they are highly relevant for success in school. We conducted an intervention study to investigate the potential impact of music training on motoric inhibition, establish causality, and demonstrate the usefulness of music training to enhance motoric inhibition. In particular, we compared the effects of two interventions, one involving music and the other sport, on motoric inhibition. In total, 25 preschoolers (15 girls, 10 boys) were randomly assigned to the two training programs. Preschoolers were trained three times per week for 20 minutes over a period of 14 weeks. Inhibition was assessed before and after the 14-week intervention period. We used the “statue” subtest of the NEPSY II, a developmental neuropsychological assessment for children, to measure inhibition. Analysis of variance with repeated measures revealed a significant interaction between intervention type (music vs. sport) and time (pre- vs. post-test). The music training, but not the sports training program, led to improved inhibition. Our findings suggest that a music training program can enhance inhibition in preschoolers.