Translation of Mycobacterium Survival Strategy to Develop a Lipo‐peptide based Fusion Inhibitor

Tarafdar, Pradip Kumar; Sardar, Avijit; Lahiri, Aritraa; Kamble, Mithila; Mallick, Amirul I.

The entry of enveloped viruses requires the fusion of viral and host cell membranes. An effective fusion inhibitor aiming at impeding such membrane fusion may emerge as a broad‐spectrum antiviral agent against a wide range of viral infections. Mycobacterium survives inside the phagosome by inhibiting phagosome‐lysosome fusion with the help of a coat protein coronin 1. Structural analysis of coronin 1 and other WD40‐repeat protein suggest that the trp‐asp (WD) sequence is placed at distorted β‐meander motif (more exposed) in coronin 1. The unique structural feature of coronin 1 was explored to identify a simple lipo‐peptide sequence (myr‐WD), which effectively inhibits membrane fusion by modulating the interfacial order, water penetration, and surface potential. The mycobacterium inspired lipo‐dipeptide was successfully tested to combat type 1 influenza virus (H1N1) and murine coronavirus infections as a ‘potential broad‐spectrum’ antiviral agent.