Rational Design of a Hybrid Peptide against Severe Acute Respiratory Syndrome Coronavirus 2 Using Melittin and Angiotensin-Converting Enzyme 2 as Pharmaceutical Agents.

Background: Management of severe acute respiratory syndrome coronavirus 2 in humans depends on the availability of vaccines or effective drugs. Studies have shown that angiotensin-converting enzyme 2 (ACE2) is responsible for binding the viral spike glycoproteins to human cells. Melittin from the bee venom of Apis melifera is a peptide with antimicrobial activities. Materials and Methods: In this study, important amino acid residues of ACE2 interacting with spike glycoproteins of the virus were described based on the ACE2-spike-glycoprotein interface. This has been previously analyzed by Robson in crystal structures of the receptors and ligands. Flexible linkers and 31 amino acid residues from N-terminal of ACE2 as coronavirus spike binding domains (SBDs) were added to 17 N-terminal amino acids of melittin (the hydrophobic motif) to construct a hybrid peptide or M-ACE2SBD. Then, secondary and tertiary structures of the peptide were predicted. Results: Docking of the hybrid peptide and coronavirus SBDs was carried out as well. Previous studies showed that toxicity and hemolytic activity of the melittin hydrophobic motif decreased in comparison to native melittin due to the lack of peptide binding to the exposed anionic lipids of the human cell membranes and hence the novel peptide can be recommended as an appropriate drug for clinical uses. Conclusion: This study has hypothesized that 17 N-terminal amino acids of the mutant melittin used in M-ACE2SBD design are potentially hydrophobic and attached coronavirus-2 through lipid envelope of the virus.

Optimization of antimicrobial efficiency of silver nanoparticles against three oral microorganisms in irreversible hydrocolloid impressions.

BACKGROUND AND OBJECTIVES: Silver nanoparticles (Ag-NPs) are potent antimicrobial agents, which have recently been used in dentistry. The aim of the current study was to optimize antimicrobial activity of Ag-NPs used in preparing irreversible hydrocolloid impressions against three microorganisms of Escherichia coli, Streptococcus mutans and Candida albicans. MATERIALS AND METHODS: After assessing antimicrobial activity of the compound using disk diffusion method, three parameters of concentration of Ag-NPs (250-1000 ppm), ratio of hydrocolloid impression material powder to water (0.30-0.50) and time of mixing (20.0-60.0 s), affecting antimicrobial activity of irreversible hydrocolloid impression materials against the three microorganisms, were optimized. This combined process was successfully modeled and optimized using Box-Behnken design with response surface methodology (RSM). Decreases in colony number of E. coli, S. mutans and C. albicans were proposed as responses. RESULTS: Qualitative antimicrobial assessments respectively showed average zone of inhibition (ZOI) of 3.7 mm for E. coli, 3.5 mm for S. mutans and 4 mm for C. albicans. For all responses, when the mixing duration and powder-to-water ratio increased, the circumstances (mixing duration of 59.38 s, powder-to-water ratio of 0.4 and Ag-NP concentration of 992 response) increased. Results showed that in optimum ppm, the proportion of decreases in colony numbers was maximum (89.03% for E. coli, 87.08% for S. mutans and 74.54% for C. albicans). Regression analysis illustrated a good fit of the experimental data to the predicted model as high correlation coefficients validated that the predicted model was well fitted with data. Values of R2Adj with R2Pred were associated to the accuracy of this model in all responses. CONCLUSION: Disinfection efficiency dramatically increased with increasing of Ag-NP concentration, powder-to-water ratio and mixing time.