<h3>Title</h3>
<h3>Interaction of Peptides with Membranes: Implications in Membrane Fusion</h3>
<p><strong><span style="text-decoration: underline;">Abstract</span> :</strong></p>
<p>Membrane fusion is an important step for the entry of the enveloped viruses into the host cells. The fusion process is catalyzed by fusion proteins present in the viral envelope. The class I virus contains a 20–25 amino acid sequence at its N-terminal of the fusion domain, which is instrumental in the fusion and is called a “fusion peptide”. However, severe acute respiratory syndrome (SARS) coronaviruses contain more than one fusion peptide sequence. We have observed that the internal fusion peptide 1 (IFP1) of SARS-CoV-2 is far more fusogenic than its N-terminal counterpart (FP) to induce hemifusion formation in a cholesterol-dependent manner. We have further developed peptide-based fusion inhibitors and tested their inhibitory efficacies. We found that in addition to the altered peptide organization and dynamics in cholesterol-containing membranes, the intrinsic negative curvature of cholesterol might be surpassing the inhibitory effect of an inhibitor peptide, TG-23. We have further demonstrated that peptide-induced water penetration into the hydrophobic region is directly correlated with its fusogenicity, and the membrane composition is adding complexity in the journey of developing peptide-based membrane fusion inhibitors.</p>