ABSTRACT
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2), emerged in late 2019 and quickly spread worldwide. SARS-CoV-2 is an enveloped virus and its entry into host cells is mediated by the spike glycoprotein (S-protein) [1]. The S-protein is composed of two subunits (S1 and S2) that contain essential domains for the viral entry mechanism, such as the fusion peptide (FP) which inserts into and disturbs the host cell membrane promoting the fusion between viral and host membranes. Despite its relevance for viral entry, there is still no consensus among scientists for its location on the S-protein and amino acid sequence, although two major candidate regions have been proposed [2, 3]. To shed light on this matter, we combined computational and experimental methods to characterize and compare the effect of the two putative SARS-CoV-2 FPs. We performed a systematic analysis of the SARS-CoV-2 putative FPs, using Molecular Dynamics simulations, to dissect how these peptides interact with the membrane. In parallel, we evaluated the putative FPs behavior in membrane model systems applying biophysical techniques. Since both FPs revealed modest fusogenic activity, we hypothesized that a longer FP or a cooperation among the individual FPs might be required to achieve fusion between viral and host membranes. Given the pivotal role of the FP to viral entry, our work provides relevant insights on the SARS-CoV-2 entry mechanism.