ABSTRACT
Background: COVID-19 is still instigating significant social and economic chaos worldwide; however, there is no approved antiviral drug yet. Here, we used in silico analysis to screen potential SARS-CoV-2 main protease (Mpro) inhibitors extracted from the essential oil of Thymus schimperi which could contribute to the discovery of potent anti-SARS-CoV-2 phytochemicals. Methods: The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of compounds were determined through SwissADME and ProToxII servers. AutoDock tools were used for molecular docking analysis studies, while Chimera, DS studio, and LigPlot were used for post-docking studies. Molecular dynamic simulations were performed for 200 ns under constant pressure. Results: All compounds exhibited a bioavailability score of ≥0.55 entailing that at least 55% of the drugs can be absorbed unchanged. Only five (9%), nine (16%) and two (3.6%) of the compounds showed active hepatotoxicity, carcinogenicity, and immunotoxicity, respectively. Except for flourazophore P, which showed a little mutagenicity, all other compounds did not show mutagenic properties. On the other hand, only pinene beta was found to have a little cytotoxicity. Five compounds demonstrated effective binding to the catalytic dyad of the SARS-CoV-2 Mpro substrate binding pocket, while two of them (geranylisobutanoate and 3-octane) are found to be the best hits that formed hydrogen bonds with Glu166 and Ser144 of SARS-CoV-2 Mpro. Conclusion: Based on our in silico analysis, top hits from Thymus schimperi may serve as potential anti-SARS-CoV-2 compounds. Further in vitro and in vivo studies are recommended to characterize these compounds for clinical applications.
ABSTRACT
Background COVID-19 is still instigating significant social and economic chaos worldwide;however, there is no approved antiviral drug yet. Here, we used in silico analysis to screen potential SARS-CoV-2 main protease (Mpro) inhibitors extracted from the essential oil of Thymus schimperi which could contribute to the discovery of potent anti-SARS-CoV-2 phytochemicals. Methods The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of compounds were determined through SwissADME and ProToxII servers. AutoDock tools were used for molecular docking analysis studies, while Chimera, DS studio, and LigPlot were used for post-docking studies. Molecular dynamic simulations were performed for 200 ns under constant pressure. Results All compounds exhibited a bioavailability score of ≥0.55 entailing that at least 55% of the drugs can be absorbed unchanged. Only five (9%), nine (16%) and two (3.6%) of the compounds showed active hepatotoxicity, carcinogenicity, and immunotoxicity, respectively. Except for flourazophore P, which showed a little mutagenicity, all other compounds did not show mutagenic properties. On the other hand, only pinene beta was found to have a little cytotoxicity. Five compounds demonstrated effective binding to the catalytic dyad of the SARS-CoV-2 Mpro substrate binding pocket, while two of them (geranylisobutanoate and 3-octane) are found to be the best hits that formed hydrogen bonds with Glu166 and Ser144 of SARS-CoV-2 Mpro. Conclusion Based on our in silico analysis, top hits from Thymus schimperi may serve as potential anti-SARS-CoV-2 compounds. Further in vitro and in vivo studies are recommended to characterize these compounds for clinical applications.
ABSTRACT
[This corrects the article DOI: 10.3389/fmicb.2022.901848.].
ABSTRACT
Due to fast transmission and various circulating SARS-CoV-2 variants, a significant increase of coronavirus 2019 infection cases with acute respiratory symptoms has prompted worries about the efficiency of current vaccines. The possible evasion from vaccine immunity urged scientists to identify novel therapeutic targets for developing improved vaccines to manage worldwide COVID-19 infections. Our study sequenced pooled peripheral blood mononuclear cells transcriptomes of SARS-CoV-2 patients with moderate and critical clinical outcomes to identify novel potential host receptors and biomarkers that can assist in developing new translational nanomedicines and vaccine therapies. The dysregulated signatures were associated with humoral immune responses in moderate and critical patients, including B-cell activation, cell cycle perturbations, plasmablast antibody processing, adaptive immune responses, cytokinesis, and interleukin signaling pathway. The comparative and longitudinal analysis of moderate and critically infected groups elucidated diversity in regulatory pathways and biological processes. Several immunoglobin genes (IGLV9-49, IGHV7-4, IGHV3-64, IGHV1-24, IGKV1D-12, and IGKV2-29), ribosomal proteins (RPL29, RPL4P2, RPL5, and RPL14), inflammatory response related cytokines including Tumor Necrosis Factor (TNF, TNFRSF17, and TNFRSF13B), C-C motif chemokine ligands (CCL3, CCL25, CCL4L2, CCL22, and CCL4), C-X-C motif chemokine ligands (CXCL2, CXCL10, and CXCL11) and genes related to cell cycle process and DNA proliferation (MYBL2, CDC20, KIFC1, and UHCL1) were significantly upregulated among SARS-CoV-2 infected patients. 60S Ribosomal protein L29 (RPL29) was a highly expressed gene among all COVID-19 infected groups. Our study suggested that identifying differentially expressed genes (DEGs) based on disease severity and onset can be a powerful approach for identifying potential therapeutic targets to develop effective drug delivery systems against SARS-CoV-2 infections. As a result, potential therapeutic targets, such as the RPL29 protein, can be tested in vivo and in vitro to develop future mRNA-based translational nanomedicines and therapies to combat SARS-CoV-2 infections.
ABSTRACT
Due to fast transmission and various circulating SARS-CoV-2 variants, a significant increase of coronavirus 2019 infection cases with acute respiratory symptoms has prompted worries about the efficiency of current vaccines. The possible evasion from vaccine immunity urged scientists to identify novel therapeutic targets for developing improved vaccines to manage worldwide COVID-19 infections. Our study sequenced pooled peripheral blood mononuclear cells transcriptomes of SARS-CoV-2 patients with moderate and critical clinical outcomes to identify novel potential host receptors and biomarkers that can assist in developing new translational nanomedicines and vaccine therapies. The dysregulated signatures were associated with humoral immune responses in moderate and critical patients, including B-cell activation, cell cycle perturbations, plasmablast antibody processing, adaptive immune responses, cytokinesis, and interleukin signaling pathway. The comparative and longitudinal analysis of moderate and critically infected groups elucidated diversity in regulatory pathways and biological processes. Several immunoglobin genes (IGLV9-49, IGHV7-4, IGHV3-64, IGHV1-24, IGKV1D-12, and IGKV2-29), ribosomal proteins (RPL29, RPL4P2, RPL5, and RPL14), inflammatory response related cytokines including Tumor Necrosis Factor (TNF, TNFRSF17, and TNFRSF13B), C-C motif chemokine ligands (CCL3, CCL25, CCL4L2, CCL22, and CCL4), C-X-C motif chemokine ligands (CXCL2, CXCL10, and CXCL11) and genes related to cell cycle process and DNA proliferation (MYBL2, CDC20, KIFC1, and UHCL1) were significantly upregulated among SARS-CoV-2 infected patients. 60S Ribosomal protein L29 (RPL29) was a highly expressed gene among all COVID-19 infected groups. Our study suggested that identifying differentially expressed genes (DEGs) based on disease severity and onset can be a powerful approach for identifying potential therapeutic targets to develop effective drug delivery systems against SARS-CoV-2 infections. As a result, potential therapeutic targets, such as the RPL29 protein, can be tested in vivo and in vitro to develop future mRNA-based translational nanomedicines and therapies to combat SARS-CoV-2 infections. Graphical