Repurposing FDA-approved drugs to fight COVID-19 using in silico methods: Targeting SARS-CoV-2 RdRp enzyme and host cell receptors (ACE2, CD147) through virtual screening and molecular dynamic simulations.

BACKGROUND: Different approaches have been proved effective for combating the COVID-19 pandemic. Accordingly, in silico drug repurposing strategy, has been highly regarded as an accurate computational tool to achieve fast and reliable results. Considering SARS-CoV-2's structural proteins and their interaction the host's cell-specific receptors, this study investigated a drug repurposing strategy aiming to screen compatible inhibitors of FDA-approved drugs against viral entry receptors (ACE2 and CD147) and integral enzyme of the viral polymerase (RdRp). METHODS: The study screened the FDA-approved drugs against ACE2, CD147, and RDRP by virtual screening and molecular dynamics (MD) simulation. RESULTS: The results of this study indicated that five drugs with ACE2, four drugs with RDRP, and seven drugs with CD147 achieved the most favorable free binding energy (ΔG < -10). This study selected these drugs for MD simulation investigation whose results demonstrated that ledipasvir with ACE2, estradiol benzoate with CD147, and vancomycin with RDRP represented the most favorable ΔG. Also, paritaprevir and vancomycin have good binding energy with both targets (ACE2 and RdRp). CONCLUSIONS: Ledipasvir, estradiol benzoate, and vancomycin and paritaprevir are potentially suitable candidates for further investigation as possible treatments of COVID-19 and novel drug development.

Gel green fluorescence ssDNA aptasensor based on carbon nanotubes for detection of anthrax protective antigen.

Bacillus anthracis, the causative agent of anthrax, is a harmful pathogen with potential ability as a biological weapon which persuades scientists to develop novel methods to detect anthrax from infected resources. In this study, a multi-walled carbon nanotube (MWCNTs)-based fluorescence aptasensor was fabricated to detect the recombinant protective antigen domain 4 (rPAD4) of Bacillus anthracis as the most important key factor in development of anthrax. First, PAD4 was recombinant expressed in E. coli and purified by Ni-NTA column. Second, the affinity of aptamer to rPAD4 was confirmed by ELAA assay. In aptasensor design, the aptamer was labeled with Gel Green and immobilized on MWCNTs. Upon the adsorption of labeled aptamer on MWCNTs, fluorescence emission was quenched. In contrast, by adding rPAD4 to hybridization reaction and incubation for 10 min, the fluorescence emission was significantly recovered to 85% compared to the control. Detection limit for the sensitivity and specificity of the aptasensor was determined 20 ng/ml and 62.5 ng/ml purified and unpurified rPAD4 protein, respectively. Also, applicability of aptasensor was showed in mouse serum sample. Finally, results indicated that nanosensor has the potential to be developed as a high-sensitive, cost-effective and fast-acting system for measuring of PA in anthrax diagnostic tests.

Evaluation of AgClNPs@SBA-15/IL nanoparticle-induced oxidative stress and DNA mutation in Escherichia coli.

The bactericidal effects of silver nanoparticles have been demonstrated in the past years. Recently, the new antimicrobial compounds of silver nanoparticles with different formulations have been developed. In this work, AgClNPs@SBA-15/IL as a new compound of Ag nanoparticles, was synthesized and characterized by XRD, TEM, SEM, FTIR, and EDX. The antibacterial activity and the molecular mechanism effects of AgClNPs@SBA-15/IL nanoparticles (SNPs) on Escherichia coli DH5α cells were investigated by analyzing the growth inhibitory, H2O2 level, catalase activity, DNA mutation, and plasmid copy number following treatment with AgClNPs@SBA-15/IL nanoparticles. In experimental results, the minimum inhibitory concentration (MIC) was observed in 75 µg/ml and the antibacterial efficacy (ABE) in CFU analysis was estimated 95.3 %. In bacterial cells treated with 75 and 100 µg/ml, H2O2 level significantly increased and catalase activity decreased compared with control. The random amplified polymorphic DNA (RAPD) was used to evaluate the effect of AgClNPs@SBA-15/IL nanoparticles in DNA damages and mutation in E. coli genome. RADP-PCR results indicated different banding patterns including appearance or disappearance of bands and differences in their intensity. Cluster analysis of the RAPD-PCR results based on genetic similarity showed genetic difference between E. coli cells treated with AgClNPs@SBA-15/IL nanoparticles, and control and phylogenetic tree were divided to two clusters. Plasmid copy number analysis indicated that after 8 h incubation of E. coli cells with 50, 75, and 100 µg/ml AgClNPs@SBA-15/IL nanoparticles, copy number of pET21a (+) significantly decreased compared with control which indicating DNA replication inhibition by Ag nanoparticles. In conclusion, the results of this study indicated that AgClNPs@SBA-15/IL nanoparticles can be used as an effective bactericidal agent against bacterial cells.