Identification of potential therapeutic targets for COVID-19 through a structural-based similarity approach between SARS-CoV-2 and its human host proteins

Background: The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide, and vaccination efficacy has been decreasing with each lineage, necessitating the need for alternative antiviral therapies. Predicting host–virus protein–protein interactions (HV-PPIs) is essential for identifying potential host-targeting drug targets against SARS-CoV-2 infection.Objective: This study aims to identify therapeutic target proteins in humans that could act as virus–host-targeting drug targets against SARS-CoV-2 and study their interaction against antiviral inhibitors.Methods: A structure-based similarity approach was used to predict human proteins similar to SARS-CoV-2 (“hCoV-2”), followed by identifying PPIs between hCoV-2 and its target human proteins. Overlapping genes were identified between the protein-coding genes of the target and COVID-19-infected patient’s mRNA expression data. Pathway and Gene Ontology (GO) term analyses, the construction of PPI networks, and the detection of hub gene modules were performed. Structure-based virtual screening with antiviral compounds was performed to identify potential hits against target gene-encoded protein.Results: This study predicted 19,051 unique target human proteins that interact with hCoV-2, and compared to the microarray dataset, 1,120 target and infected group differentially expressed genes (TIG-DEGs) were identified. The significant pathway and GO enrichment analyses revealed the involvement of these genes in several biological processes and molecular functions. PPI network analysis identified a significant hub gene with maximum neighboring partners. Virtual screening analysis identified three potential antiviral compounds against the target gene-encoded protein.Conclusion: This study provides potential targets for host-targeting drug development against SARS-CoV-2 infection, and further experimental validation of the target protein is required for pharmaceutical intervention

Antimicrobial Analysis of Biosynthesized Lectin-Conjugated Gold Nanoparticles

To enhance the bioactivity of molecules through nanoparticles is being tested which has potential use in sustained-release drug delivery systems and to enhance the therapeutic effectiveness of drugs. Our current investigation s is to conjugate lectin to that of a gold nanoparticle (GNP) surface without disturbing the bioactive properties and enhances the antibacterial activity of lectin. Au-lectin nanoparticles were checked for their hemagglutination activity, characterized by transmission electron microscopy (TEM) and UV-visible spectrophotometer. The antibacterial effect of nanoparticle lectin, Au salt nanoparticle, and conjugated Au-lectin was estimated by Kirby-Bauer disc method; MICs were determined by microbroth dilution and compared with ciprofloxacin. These tests were done using known species of bacterial strain of multidrug resistant. The hemagglutination activity of lectin was improved to fourfold after purification. Lectin and Au nanoparticles combined had a significant effect on the inhibition of bacterial growth. No significant differences were observed in the inhibition zone diameters from killed bacteria and its supernatant towards any of the tested organisms. Lectin-conjugated gold particles showed good efficacy as antimicrobial agents and the nanoparticle-killed bacteria to work against the viable population of the same bacterium and/or other bacterial species too

Silver Nanoparticles Loaded on Chitosan-g-PVA Hydrogel for the Wound-Healing Applications

Silver nanoparticle composites have abundant biomedical applications due to their unique antibacterial properties. In the current work, green tea leaf extract was used as a natural reducing agent to synthesize AgNPs (AgNPs) using microwave irradiation technology. Furthermore, microwave irradiation has been used for the preparation of AgNPs/chitosan (Ch) grafted polyvinyl alcohol (PVA) hydrogel samples. To approve the accomplishment of AgNPs hydrogel polymer, UV-spectrum, TEM, and FT-IR spectrum analyses and the release of silver ions, actions were taken. The wound-healing ability of the prepared hydrogel samples was measured via both the in vitro (fibroblast cells) and the in vivo using rat models. It was found that chitosan-grafted polyvinyl alcohol, including AgNPs, exhibited excellent antibacterial activity against E. coli and S. aureus using the agar diffusion method. It can be said that microwave irradiation was successful in creating a hydrogel that contained silver nanoparticles. A wound that was still open was successfully treated with these composites

Level of apoptosis in Saudi patients with a defect in Glucose-6-phosphate dehydrogenase (G6PD)

Introduction: Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme responsible for the production of NADPH pathway. Mutation in G6PD gene results in abnormal functional and structural changes in red blood cells (RBCs). The aim of the current study is to compare the levels of apoptosis in Saudi people suffering from G6PD deficiency. Materials and methods: Twenty samples from unrelated Saudi children and neonates between the ages of 1 month to 10 years were collected. Ten ml Blood samples were collected by venipuncture in EDTA tubes, and hematological parameters assessed using Coulter Counter Analyzer. MNC cells were isolated. Apoptotic leukocytes were determined and concentaration of IL-107 release was measured using the FACS machine. Result: There was a significant increase in white blood cells (WBCs) count in G6PD deficiency group compared to healthy controls. Also, there was a sgnificant increase in the level of apoptosis observed in the freshly isolated RBCs obtained from G6PD deficiency patients. Conclusion: The findings may indicate that apoptosis of RBCs represents an important factor in the pathogenesis of G6PD

Phenolic phytochemistry, in vitro, in silico, in vivo, and mechanistic anti-inflammatory and antioxidant evaluations of Habenaria digitata

Excessive and imbalance of free radicals within the body lead to inflammation. The objective of the current research work was to explore the anti-inflammatory and antioxidant potential of the isolated compounds from Habenaria digitata. In this study, the isolated phenolic compounds were investigated for in vitro and in vivo anti-inflammatory potential along with the antioxidant enzyme. The anti-inflammatory and antioxidant potential of the phenolic compounds was assayed via various enzymes like COX-1/2, 5-LOX and ABTS, DPPH, and H2O2 free radical enzyme inhibitory assay. These compounds were also explored for their in vivo antioxidant activity like examining SOD, CAT, GSH-Px, and MDA levels in the brain, heart, and liver. The anti-inflammatory potential was evaluated using the carrageenan-induced pleurisy model in mice. On the basis of initial screening of isolated compounds, the most potent compound was further evaluated for the anti-inflammatory mechanism. Furthermore, the molecular docking study was also performed for the potent compound. The phenolic compounds were isolated and identified by GC-MS/NMR analysis by comparing its spectra to the library spectra. The isolated phenolic compounds from H. digitata were 5-methylpyrimidine-24,4-diol (1), 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (2), 2-isopropyl-5-methylphenol (3), 3-methoxy-4-vinylphenol (4), and 2,6-dimethoxy-4-vinylphenol (5). In in vitro antioxidant assay, the most potent compound was compound 1 having IC50 values of 0.98, 0.90, and 5 μg/mL against ABTS, DPPH, and H2O2, respectively. Similarly, against COX1/2 and 5-LOX ,compound 1 was again the potent compound with IC50 values of 42.76, 10.70, and 7.40 μg/mL. Based on the in vitro results, compound 1 was further evaluated for in vivo antioxidant and anti-inflammatory potential. Findings of the study suggest that H. digitata contains active compounds with potential anti-inflammatory and antioxidant effects. These compounds could be screened as drug candidates for pharmaceutical research, targeting conditions associated with oxidative stress and inflammatory conditions in medicinal chemistry and support their ethnomedicinal use for inflammation and oxidative stress

Stability indicating HPLC method for the simultaneous analysis of Gatifloxacin and Loteprednol in eyedrop formulation using design of experiment approach

187-197Design of experiment (DOE) assisted simple, rapid, precise and accurate stability indicating HPLC method has been developed for simultaneous estimation of Gatifloxacin (GTF) and Loteprednol (LOT) along with their forced degradation products. The developed method has been optimized and developed by using central composite design (CCD) in response surface methodology (RSM). Trails have been undertaken and ratio of phosphate buffer in mobile phase, pH of buffer and flow rate are selected as factors. Resolution, tailing factor (GTF) and tailing factor (LOTE) are selected for determining the system response in the process of method optimization. The responses have been optimized using the Derringer’s desirability function. The effective separation is achieved on Phenomenex EVO-C18 column (250 mm x 4.6 mm i.d, 5 μm particle size) with mobile composed of 10 mM phosphate buffer, pH 3.5 and organic phase composed of mixture of acetonitrile and methanol 60:40 % v/v, the flow rate was 1.0 mL/min, the signals were detected at 267 nm. The developed method was validated for linearity, accuracy, precision, and robustness. The method was applied successfully for stability samples

Evaluation of Anti-Venom Potential of <em>Areca catechu</em> Seed Extract on <em>Bungarus caeruleus</em> Venom

Areca catechu seeds and their extract/s are currently used to treat various ailments and infections including snakebites. The purpose of this investigation was to assess the inhibiting/neutralizing effect of ethyl acetate and aqueous ethanolic seed extracts of A. catechu on Bungarus caeruleus (krait) venom. The enzyme activities and their inhibition were evaluated using standard procedures (in vitro). In vivo studies were conducted using chick embryos and murine models. The extracts inhibited hyaluronidase and phospholipase A2 activities. Protease activity was neutralized by the aqueous ethanolic extract only. The IC50 value of aqueous ethanolic extract for hyaluronidase was 0.001 g/mL, while that for the ethyl acetate extract for phospholipase A2 was 0.006 g/mL. In addition, both the extracts neutralized the indirect hemolysis and fibrinogenolytic activity induced by B. caeruleus venom. The LD50 for the chick embryos was 4.9 µg/egg. The 50 and 100 µg aqueous ethanolic extracts neutralized the LD50 and the challenging dose (3LD50) of venom effectively in the chick embryo model. The LD50 of B. caeruleus venom in mice was 0.1927 µg/kg; the extract extended the survival time of the mice from 25 min to 30 and 35 min in 1:10 and 1:20 ((w/w) venom:extract) ratios, respectively. The extract also neutralized myotoxic activity. The A. catechu seed extract showed promising inhibitory properties against B. caeruleus venom. In this regard, academia and industries should work collaboratively to develop and formulate a cost-effective first-aid drug

Table2_Identification of potential therapeutic targets for COVID-19 through a structural-based similarity approach between SARS-CoV-2 and its human host proteins.xlsx

Background: The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide, and vaccination efficacy has been decreasing with each lineage, necessitating the need for alternative antiviral therapies. Predicting host–virus protein–protein interactions (HV-PPIs) is essential for identifying potential host-targeting drug targets against SARS-CoV-2 infection.Objective: This study aims to identify therapeutic target proteins in humans that could act as virus–host-targeting drug targets against SARS-CoV-2 and study their interaction against antiviral inhibitors.Methods: A structure-based similarity approach was used to predict human proteins similar to SARS-CoV-2 (“hCoV-2”), followed by identifying PPIs between hCoV-2 and its target human proteins. Overlapping genes were identified between the protein-coding genes of the target and COVID-19-infected patient’s mRNA expression data. Pathway and Gene Ontology (GO) term analyses, the construction of PPI networks, and the detection of hub gene modules were performed. Structure-based virtual screening with antiviral compounds was performed to identify potential hits against target gene-encoded protein.Results: This study predicted 19,051 unique target human proteins that interact with hCoV-2, and compared to the microarray dataset, 1,120 target and infected group differentially expressed genes (TIG-DEGs) were identified. The significant pathway and GO enrichment analyses revealed the involvement of these genes in several biological processes and molecular functions. PPI network analysis identified a significant hub gene with maximum neighboring partners. Virtual screening analysis identified three potential antiviral compounds against the target gene-encoded protein.Conclusion: This study provides potential targets for host-targeting drug development against SARS-CoV-2 infection, and further experimental validation of the target protein is required for pharmaceutical intervention.</p

Table3_Identification of potential therapeutic targets for COVID-19 through a structural-based similarity approach between SARS-CoV-2 and its human host proteins.xlsx

Background: The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide, and vaccination efficacy has been decreasing with each lineage, necessitating the need for alternative antiviral therapies. Predicting host–virus protein–protein interactions (HV-PPIs) is essential for identifying potential host-targeting drug targets against SARS-CoV-2 infection.Objective: This study aims to identify therapeutic target proteins in humans that could act as virus–host-targeting drug targets against SARS-CoV-2 and study their interaction against antiviral inhibitors.Methods: A structure-based similarity approach was used to predict human proteins similar to SARS-CoV-2 (“hCoV-2”), followed by identifying PPIs between hCoV-2 and its target human proteins. Overlapping genes were identified between the protein-coding genes of the target and COVID-19-infected patient’s mRNA expression data. Pathway and Gene Ontology (GO) term analyses, the construction of PPI networks, and the detection of hub gene modules were performed. Structure-based virtual screening with antiviral compounds was performed to identify potential hits against target gene-encoded protein.Results: This study predicted 19,051 unique target human proteins that interact with hCoV-2, and compared to the microarray dataset, 1,120 target and infected group differentially expressed genes (TIG-DEGs) were identified. The significant pathway and GO enrichment analyses revealed the involvement of these genes in several biological processes and molecular functions. PPI network analysis identified a significant hub gene with maximum neighboring partners. Virtual screening analysis identified three potential antiviral compounds against the target gene-encoded protein.Conclusion: This study provides potential targets for host-targeting drug development against SARS-CoV-2 infection, and further experimental validation of the target protein is required for pharmaceutical intervention.</p

Table1_Identification of potential therapeutic targets for COVID-19 through a structural-based similarity approach between SARS-CoV-2 and its human host proteins.xlsx

Background: The COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide, and vaccination efficacy has been decreasing with each lineage, necessitating the need for alternative antiviral therapies. Predicting host–virus protein–protein interactions (HV-PPIs) is essential for identifying potential host-targeting drug targets against SARS-CoV-2 infection.Objective: This study aims to identify therapeutic target proteins in humans that could act as virus–host-targeting drug targets against SARS-CoV-2 and study their interaction against antiviral inhibitors.Methods: A structure-based similarity approach was used to predict human proteins similar to SARS-CoV-2 (“hCoV-2”), followed by identifying PPIs between hCoV-2 and its target human proteins. Overlapping genes were identified between the protein-coding genes of the target and COVID-19-infected patient’s mRNA expression data. Pathway and Gene Ontology (GO) term analyses, the construction of PPI networks, and the detection of hub gene modules were performed. Structure-based virtual screening with antiviral compounds was performed to identify potential hits against target gene-encoded protein.Results: This study predicted 19,051 unique target human proteins that interact with hCoV-2, and compared to the microarray dataset, 1,120 target and infected group differentially expressed genes (TIG-DEGs) were identified. The significant pathway and GO enrichment analyses revealed the involvement of these genes in several biological processes and molecular functions. PPI network analysis identified a significant hub gene with maximum neighboring partners. Virtual screening analysis identified three potential antiviral compounds against the target gene-encoded protein.Conclusion: This study provides potential targets for host-targeting drug development against SARS-CoV-2 infection, and further experimental validation of the target protein is required for pharmaceutical intervention.</p