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Purpose: The involvement of Wnt-8b in Wnt signaling pathway leads to various cancers. The purpose of this study was to determine the therapeutic compounds from the available library by targeting Wnt-8b using molecular docking analyses. Methods: Threading and comparative modeling approaches were employed to predict the 3D structure of Wnt-8b. Sixty-eight models were evaluated using molprobity, ERRAT and rampage evaluation tools and the model having 82.456 % overall quality value was selected for further analyses. The acyl group was added to the suitable model to satisfy the hydrophobic nature of the Wnt-8b. Literature-derived compounds were selected for comparative molecular docking studies using GOLD, AutoDock and AutoDock Vina. Furthermore, docked complexes were analyzed and visualized using Chimera and Ligplot. Results: The compound ZINC04029462 exhibited high binding potential with Wnt-8b and palmitoleic acid and was found common among top 20 compounds of each tool. His-183, Val-185, Ser-186, Gly-187, Ser-188 and Thr-190 residues commonly interacted with compounds and palmitoleic acid and considered as potential interacting residues. Conclusion: Common interacting residues from top 20 compounds of each tool suggest that these compounds may be utilized to inhibit aberrant expression of Wnt-8b. The common inhibitor ZINC04029462 may act as a lead compound for further drug designing against Wnt family.

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.