Sars-CoV-2 Envelope and Membrane Proteins: Structural Differences Linked to Virus Characteristics?

Abstract

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

Figure 1

Multiple sequence alignment among Sars-CoV-2 Envelope protein variants and a set of the most similar homologous proteins. The sequence labelled Sars-CoV-2 corresponds to the reference sequence identified by the RefSeq code YP_009724392. Red lines below the alignment indicate the changed sites discussed in the text. Blu background denotes conserved alignment positions.

Figure 2

Three-dimensional model of the viroporin-like tetrameric assembly of the E protein from Sars-CoV-2 represented as a cartoon model. Residues corresponding to the mutated sites indicated in Figure 1 are displayed as transparent space-filling spheres and labelled with the amino acid one-letter code. The C-terminal segments of the model are reported for completeness. However, they convey no structural information due to lack of a corresponding segment in the structural template used in homology modelling. Structure in panel (b) is rotated by approximately 180° along the x axis with respect to the orientation shown in panel (a).

Figure 3

Multiple sequence alignment among Sars-CoV-2 M protein variants and a set of most similar homologous proteins. The sequence label Sars-CoV-2 indicates the reference sequence identified by the RefSeq code YP_009724393. Red box indicates the variant sites at the N-terminal discussed in the text. Numbered red bars under the multiple alignment mark the prediction of transmembrane helices. The location of the connect loop with respect to the virion surface is indicated as “in” or “out”. Blu background denotes conserved alignment positions.

Figure 4

I-Tasser model of the Membrane protein represented as cartoon model. Variant positions are displayed as transparent space-filling spheres and labelled with the amino acid one-letter code.