Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Poster Abstracts

59-POS Board 20 REVERSAL OF THE FUSION CATALYTIC ROLE OF SARS-COV-2 FUSION PEPTIDE BY RESTRICTING THE N -TERMINUS: IMPLICATIONS TO TACKLE VIRAL INFECTION Avijit Sardar 1 ; Tapas Bera 2 ; Santosh Kumar Samal 1 , Samit Guha 2 ; Pradip K. Tarafdar* 1 ; 1 Department of Chemical Sciences and Department of Biological Sciences, Indian Institute of Science Education and Research, Kolkata, Mohanpur-741246, India 2 Department of Chemistry, Jadavpur University, Kolkata-700032, India Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the fusion peptide (FP) of the spike protein is essential. The FP interacts with the membrane via N-terminus and further perturbation leads to membrane fusion. Interestingly, by attaching a myristoyl lipid linker at the N -terminus of the fusion peptide, referred to as N-myr-FP, the free dive to the host membrane was hypothesized to be restricted. In the presence of the membrane, this caused a noticeable change in the secondary structure of the FP and N-myr-FP. As a result, in comparison to FP without lipidation, the directions of membrane contact as well as the physical characteristics of the membrane, such as membrane interfacial order, water penetration, and membrane surface potential, were reversed. The N-myr-FP inhibits membrane fusion and it was utilized to restrict murine coronavirus infection by reducing syncytia formation and viral plaque formation in L2 cells. The strategy of restricting the free dive of the N -terminus of the FP through lipidation to reverse the fusion catalytic role of FP to an anti-catalytic one is first on its own and may offer a new paradigm to combat enveloped viral infections.

113