Synthesis of coronin 1 inspired trimeric lipo-peptides

Bhowmick, Debosmita (2023) Synthesis of coronin 1 inspired trimeric lipo-peptides. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Debosmita Bhowmick (18MS032)) Thesis_18MS032.pdf - Submitted Version Restricted to Repository staff only Download (2MB)

Abstract

Viral infections are a constant threat to humankind. Viruses can instigate several chronic diseases, and several viruses can also cause cancer. In pandemic and epidemic form, viruses can wipe out a population and significantly impact society- a recent example being the COVID-19 pandemic by the SARS-CoV-2 virus. However, the attempts undertaken to tackle them need further tuning as they are not highly effective. Researchers have even predicted the emergence of new viral diseases of zoonotic origin, constituting a future menace. In such a scenario, the development of prophylactics and therapeutics requires immediate attention. For bacterial infections, we have broad-spectrum antibiotics, but for viral infections, we currently have the ‘one-bug, one-drug’ approach. Mycobacterium tuberculosis utilises Coronin 1, a WD40 coat protein on host cells, to ensure survival in host cells by preventing phagosome-lysosome fusion. Inspired by this survival strategy, our group previously worked on two small lipo-peptides based on Trp-Asp (WD) sequence. Both lipo-peptides have shown promising results in combating viral infections. To further improve the efficacy of the parent lipo-peptide as a membrane fusion inhibitor, we tried synthesizing a trimeric lipo-peptide containing three WD units and investigating its activity. In the meantime, we also attempted to prepare different molecular backbones and observe if they have any role. An analogue myr-citric(WD)₃ exhibited positive results in the model membrane system and can be considered a potential candidate for a broad-spectrum antiviral agent.

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