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Context: Cancer is the leading cause of death in the human population, ensuing from the accumulation of damage to genetic materials and affecting various parts of the organs. This review is focused on the cell signaling cross-talk mechanism of colorectal cancer (CRC) and its regulations. Genomic instability acts as the major driving force for CRC. The major CRC cascade mechanisms such as Wnt, Ras, TOPK, p53, and ubiquitin pathways were discussed. These interlinked signals cross-talk with one another in various regulatory mechanisms and play a unique role in CRC. Evidence Acquisition: The major cross-talking signals of CRC are the most significant part of this review. Wnt is a resource and center of axis for cross-talk and interlinked signaling mechanism. Wnt/β-catenin signaling was regulated by frizzled receptor, co-factors, Ras, TOPK, and many other mechanisms; related literature of CRC were collected through a literature survey and categorized using the keywords. The pathways with high specificity interlinked with Wnt were identified and used as the major targets for this review. Results and Conclusion: The interlinked signaling pathways and gene networks were explained with their specificity role in CRC. We highlighted the major regulatory signaling and interlinked pathways of CRC, as new multi targets approach. Furthermore, we discussed the potent targeted genes, bio-markers for a better prognosis, and therapies for CRC patients. Through highlighting the gene cross-talking signaling cascade; we have provided the source for gene network interaction and targeted therapy. This study paves the way for multi-targeting of interlinked pathways and suggesting these would be perfect for suppressing of CRC. The signaling pathways discussed in this review are not only focused on CRC but also the new potent targets and bio-markers for different types of cancers. Targeting multiple interlinked pathways could be useful for developing new potential bio-markers for treatment and diagnosis purposes.

COVID-19 is more virulent and challenging to human life. In India, the Ministry of AYUSH recommended some strategies through Siddha, homeopathy, and other methods to effectively manage COVID-19 (Guidelines for AYUSH Clinical Studies in COVID-19, 2020). Kabasura Kudineer and homeopathy medicines are in use for the prevention and treatment of COVID-19 infection; however, the mechanism of action is less explored. This study aims to understand the antagonist activity of natural compounds found in Kabasura Kudineer and homeopathy medicines against the SARS-CoV-2 using computational methods. Potential compounds were screened against NSP-12, NSP-13, NSP-14, NSP-15, main protease, and spike proteins. Structure-based virtual screening results shows that, out of 14,682 Kabasura Kudineer compounds, the 250395, 129677029, 44259583, 44259584, and 88583189 compounds and, out of 3,112 homeopathy compounds, the 3802778, 320361, 5315832, 14590080, and 74029795 compounds have good scoring function against the SARS-CoV-2 structural and nonstructural proteins. As a result of docking, homeopathy compounds have a docking score ranging from −5.636 to 13.631 kcal/mol, while Kabasura Kudineer compounds have a docking score varying from −8.290 to −13.759 kcal/mol. It has been found that the selected compounds bind well to the active site of SARS-CoV-2 proteins and form hydrogen bonds. The molecular dynamics simulation study shows that the selected compounds have maintained stable conformation in the simulation period and interact with the target. This study supports the antagonist activity of natural compounds from Kabasura Kudineer and homeopathy against SARS-CoV-2’s structural and nonstructural proteins.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.