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Exosomal nanoparticles are cell-derived nano-sized vesicles in size range of 30-150nm formed by the inward infolding of the cell membrane. They are encased in a lipid bilayer membrane and contain a wide variety of proteins and nucleic acids according to the characteristics of their parent cell. They are involved in intercellular communication. Their specific structural and inherent properties are helpful in therapeutics and as biomarkers in diagnostics. Since they are biomimetic, these small-sized nanoparticles pose many advantages if used as a drug carrier vehicle. In cancer, the exosomal nanoparticles have both stimulatory and inhibitory activity towards immune responses and hence it is used in immunotherapy. They can also carry chemotherapeutic agents specifically to the target site minimizing their targetability concerns. Chemoimmunotherapy(CIT) is a synergistic approach in which both chemotherapy and immunotherapy are utilized to benefit each other. Exosomal nanoparticles(NPs) have an essential role in delivering CIT agents into tumor tissues. Most advanced studies in CIT take place in the stimulator of interferon genes(STING) signaling pathway, where the STING activation supported by chemotherapy-induced an increase in immune surveillance through the help of exosomal NPs. Dendritic cell(DC) derived exosomes, as well as Mesenchymal stem cells (MSC), are abundantly used in immunotherapy and hence their support can be used in chemoimmunotherapy(CIT) for multifaceted benefits.

Purpose COVID-19 pandemic has become worse with the difficulty of tracing the virus or phase of the coronaviral cycle inside the host, the failure of currently employed drugs over a vast population and the evolution of newer multiple strains. This work aimed to investigate and design novel molecules that can tackle coronaviral disease more effectively Methods The study was initiated with a drug repurposing approach to screen the existing drugs against multiple receptors of the initial strain, alpha coronavirus, through various in-silico analyses. The best hits were selected on their binding affinity towards most targets and their physicochemical properties. Top hits were assessed for their efficiency against multiple coronavirus strains, such as delta and Omicron and their Ligand-protein complexation stability through molecular dynamics study. They were further fragmented and subjected to fragment-based drug designing (FBDD) to give rise to novel molecules. Results Amentoflavone, Lopinavir and Teniposide were identified as the most effective ligands against multiple receptors of the corona viral protein through the drug repurposing studies. These drugs were fragmented, linked together in multiple fashions through the process of clustering and growing to give rise to some newly designed drugs. The novel compounds exhibited more affinity towards the multiple strains of coronavirus than their parent counterparts did. Conclusion Overall, the study resulted in the generation of novel moieties with promising activity towards the multiple strains of coronavirus through FBDD initiated through a multi-targeting anti-covid drug repurposing study.