Fusion inhibition of sterol-linked dipeptides: Role of membrane composition and linker

Panda, Bishvanwesha (2022) Fusion inhibition of sterol-linked dipeptides: Role of membrane composition and linker. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Bishvanwesha Panda (16MS133)) 16MS133_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (4MB)

Abstract

Many recently appeared infectious diseases are viral in origin, and they create a major threat on global health and the economy. It is very necessary for development of highly productive broad-spectrum therapeutic agents to take forward these diseases.1 To design effective broadspectrum therapeutics, there is a need to target common but important pathway of virus life cycle. Interestingly, many 'Enveloped' viruses such as influenza, corona, HIV, dengue, zika have lipid bilayers as an integral part of their structure. They enter into the host cells via membrane fusion process to deliver the genetic material and initiate the replication. We believe that blocking of membrane fusion is an important strategy to develop a broad-spectrum antiviral compound. In this project we aim to develop a fusion inhibitor, which may act as an anti-viral agent. To design an effective fusion inhibitor, we look at look at the intracellular survival strategy of Mycobacterium tuberculosis and its circumvention from phagosomelysosome fusion. Mycobacterium recruits a coat protein Coronin 1 (with WD repeat domain) to the phagosome which plays a very important role in the survival of bacteria via inhibiting phagosomal and lysosomal fusion (W=tryptophan, D=aspartic acid). In a recent study, we have shown that myristoylated-WD dipeptide blocks membrane fusion and exhibit anti-viral properties. In the present study, we have investigated the role of a sterol-linker and terminal aspartic acid to inhibit membrane fusion.

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