Membrane binding proteins of coronaviruses

J Alsaadi, Entedar A; Jones, Ian M

In terms of sequence and location precise fusion peptides (FP) have yet to be defined for all CoVs [25] as recognition of the FP motif within the large spike protein can be difficult. However, bioinformatics analysis suggests that at least part of the fusion peptide is located near the N-terminus of S2 where a conserved motif with properties consistent with those expected of an FP, IEDLLF, occurs across the CoV family. This motif demonstrates very little variation and when substitutions are found, they are conservative replacements consistent with an essential function [26, 27] . The motif is not located at the N-terminus of HR1 as suggested in some S protein cleavage maps (e.g., ref [21] ) but immediately follows the second, S2 cleavage site, originally mapped in SARS-CoV S and later in MERS CoV S [26, 28, 29] . A sequence which includes this motif has been shown directly for SARS-CoV to act as a fusion peptide when tested in an in vitro binding assay with multilamellar vesicles (MLVs) where it reorders membranes in a calcium-dependent manner [30] .