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Viruses ; 14(4)2022 03 28.
Article in English | MEDLINE | ID: covidwho-1792421


Focusing on the transmembrane domains (TMDs) of viral fusion and channel-forming proteins (VCPs), experimentally available and newly generated peptides in an ideal conformation of the S and E proteins of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and SARS-CoV, gp41 and Vpu, both of human immunodeficiency virus type 1 (HIV-1), haemagglutinin and M2 of influenza A, as well as gB of herpes simplex virus (HSV), are embedded in a fully hydrated lipid bilayer and used in multi-nanosecond molecular dynamics simulations. It is aimed to identify differences in the dynamics of the individual TMDs of the two types of viral membrane proteins. The assumption is made that the dynamics of the individual TMDs are decoupled from their extra-membrane domains, and that the mechanics of the TMDs are distinct from each other due to the different mechanism of function of the two types of proteins. The diffusivity coefficient (DC) of the translational and rotational diffusion is decreased in the oligomeric state of the TMDs compared to those values when calculated from simulations in their monomeric state. When comparing the calculations for two different lengths of the TMD, a longer full peptide and a shorter purely TMD stretch, (i) the difference of the calculated DCs begins to level out when the difference exceeds approximately 15 amino acids per peptide chain, and (ii) the channel protein rotational DC is the most affected diffusion parameter. The rotational dynamics of the individual amino acids within the middle section of the TMDs of the fusion peptides remain high upon oligomerization, but decrease for the channel peptides, with an increasing number of monomers forming the oligomeric state, suggesting an entropic penalty on oligomerization for the latter.

COVID-19 , Ion Channels , Molecular Dynamics Simulation , Viral Fusion Proteins , Amino Acids , Humans , Ion Channels/ultrastructure , Peptides/chemistry , SARS-CoV-2 , Viral Fusion Proteins/ultrastructure
Nat Commun ; 11(1): 2688, 2020 05 27.
Article in English | MEDLINE | ID: covidwho-432476


Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential. Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein. Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike. Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs. We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes. Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.

Glycoproteins/immunology , Middle East Respiratory Syndrome Coronavirus , Polysaccharides , Spike Glycoprotein, Coronavirus/immunology , Viral Fusion Proteins/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cryoelectron Microscopy , Epitopes/chemistry , Epitopes/immunology , Epitopes/metabolism , Glycoproteins/chemistry , Glycoproteins/ultrastructure , Glycosylation , HEK293 Cells , HIV-1/immunology , HIV-1/metabolism , Humans , Immune Evasion/physiology , Lassa virus/immunology , Lassa virus/metabolism , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/metabolism , Orthomyxoviridae/immunology , Orthomyxoviridae/metabolism , Polysaccharides/chemistry , Polysaccharides/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/ultrastructure , Viral Fusion Proteins/chemistry , Viral Fusion Proteins/ultrastructure , Viral Proteins/chemistry , Viral Proteins/immunology , Viral Proteins/ultrastructure