Coronin 1 derived tryptophan-aspartic acid containing peptides inhibit membrane fusion.

Membrane fusion is an integral part of the viral infection. The fusion between an enveloped virus and a host cell is the first step for viral infection. It has been a long-standing effort to develop anti-viral therapies involving inhibitors that block the fusion between virus and host cell. However, these inhibitors are highly specific against a particular virus. Development of generic inhibitors is extremely essential in the current scenario to overcome emerging and re-emerging contagious diseases that cause millions of fatalities every year. In this work, we have studied the effect of three different peptides derived from a phagosomal protein coronin 1. Coronin 1 is being recruited at the phagosomal membrane of Mycobacterium infected host cells and is implicated in preventing lysosomal fusion. Interestingly, coronin 1 contains tryptophan-aspartic acid repeats, which are conserved across species. In order to understand the mechanistic basis of coronin 1 function, we designed peptides that contain conserved tryptophan-aspartic acid region, and evaluated their membrane binding, effect on membrane fusion, depth-dependent membrane ordering and water penetration into the membrane. Our results demonstrate that these peptides exclusively bind to membranes in presence of negatively charged lipids and do not influence lipid mixing. However, two peptides, TG-23 and GL-22, substantially reduce the extent of content mixing. The reduction in content mixing in presence of TG-23 and GL-22 could be interpreted in terms of their inhibitory effect on water penetration into the membrane. We envisage that these results will contribute to the development of the generic peptide-based membrane fusion inhibitors.