Structure and dynamics of the SARS‐CoV‐2 envelope protein monomer

Abstract

Coronaviruses, especially severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), present an ongoing threat to human wellbeing. Consequently, elucidation of molecular determinants of their function and interaction with the host is an important task. Whereas some of the coronaviral proteins are extensively characterized, others remain understudied. Here, we use molecular dynamics simulations to analyze the structure and dynamics of the SARS‐CoV‐2 envelope (E) protein (a viroporin) in the monomeric form. The protein consists of the hydrophobic α‐helical transmembrane domain (TMD) and amphiphilic α‐helices H2 and H3, connected by flexible linkers. We show that TMD has a preferable orientation in the membrane, while H2 and H3 reside at the membrane surface. Orientation of H2 is strongly influenced by palmitoylation of cysteines Cys40, Cys43, and Cys44. Glycosylation of Asn66 affects the orientation of H3. We also observe that the monomeric E protein both generates and senses the membrane curvature, preferably localizing with the C‐terminus at the convex regions of the membrane; the protein in the pentameric form displays these properties as well. Localization to curved regions may be favorable for assembly of the E protein oligomers, whereas induction of curvature may facilitate the budding of the viral particles. The presented results may be helpful for a better understanding of the function of the coronaviral E protein and viroporins in general, and for overcoming the ongoing SARS‐CoV‐2 pandemic.

Structural Dynamics of the SARS-CoV-2 Spike Protein: A 2-Year Retrospective Analysis of SARS-CoV-2 Variants (from Alpha to Omicron) Reveals an Early Divergence between Conserved and Variable Epitopes

“…SARS-CoV-2 evolution has been extensively studied by computational approaches [44,[57][58][59][60][61][62]. Our retrospective analysis of SARS-CoV-2 variants revealed an early divergence between conserved (ADE) and variable (neutralizing) epitopes which is based on their localization on the spike protein.…”

The Flexible, Extended Coil of the PDZ-Binding Motif of the Three Deadly Human Coronavirus E Proteins Plays a Role in Pathogenicity

“…Over the course of the COVID-19 pandemic, the SARS-CoV-2 spike (S) protein has incurred many mutations [81][82][83][84][85], raising the concern that other viral proteins might also have incurred mutations. However, several studies have analyzed sequenced genomes obtained from COVID-19 databases and reported minimal mutations in the SARS-CoV-2 E gene [85][86][87][88][89][90][91], remarking that the E protein and its properties are highly conserved [90][91][92][93][94]. We therefore conclude that the full-length, 3D structures predicted for all five of the E proteins successfully passed quality assessment, and based on the low RSMD values, we are confident that the correct protein folds were assigned to the respective protein sequences.…”

“…Other studies have also modelled hCoV E proteins, but they have focused exclusively on the more virulent hCoV E proteins and excluded the less virulent ones [36,92,93,95]. Some studies have only constructed partial models of SARS-CoV-2 E using 5X29 as template [95] or SARS-CoV-1, -2, and MERS-CoV E proteins from the 2MM4 template [92].…”

“…One study, interestingly, used a full-length SARS-CoV-2 E model that was constructed from machine learning and physics-based refinement [93], but the model was not published. Only one other study constructed full-length models of SARS-CoV-1 and -2 E similar to our models but used only 2MM4 as template [36].…”

Molecular dynamics studies reveal structural and functional features of the SARS‐CoV‐2 spike protein

“…Other attempts against MPro were done [ 130 , 131 , 132 , 133 ] but require further experimental data to validate the hypothesis. The RNA polymerase, [ 134 ] as well as the nucleocapsid, [ 135 ] and envelope protein [ 136 ] were proposed as a druggable target, but these studies will require further confirmation by experimental data to verify whether NSPs could be considered viable targets.…”