Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the global COVID-19 pandemic. Understanding its intricate physical structure provides valuable insights for scientific research and public health efforts, helping to comprehend its behavior and develop effective countermeasures.
Overall Viral Architecture
SARS-CoV-2 virions exhibit a generally spherical shape, although some can appear pleomorphic. Their typical diameter ranges from approximately 50 to 200 nanometers (nm), with some studies reporting sizes between 60 to 140 nm. This small size means that even N95 masks, designed to filter particles 0.3 micrometers (µm) or less, are effective at capturing most free virions.
An outer lipid envelope encases the internal components of the virus. This envelope is derived from the host cell’s own membranes, specifically from the endoplasmic reticulum (ER) and Golgi intermediate compartment during viral assembly and budding. The viral envelope, however, has a distinct lipid composition, consisting mainly of phospholipids with limited cholesterol or sphingolipids, which differentiates it from host cell membranes. Various proteins are embedded within this envelope, playing diverse roles in the viral life cycle.
The Spike Protein
The Spike (S) protein is a distinctive feature on the surface of SARS-CoV-2, giving coronaviruses their characteristic “corona” or crown-like appearance under electron microscopy. These bulbous projections vary in length, typically measuring around 9 to 12 nm. Each virion is estimated to have approximately 90 spike trimers on its surface, with each trimer composed of three identical monomers.
The Spike protein is composed of two functional subunits: S1 and S2. The S1 subunit contains the receptor-binding domain (RBD), which is responsible for attaching the virus to host cells. It specifically binds to the human angiotensin-converting enzyme 2 (ACE2) receptor, which is abundant on the surface of type II alveolar cells in the lungs, among other locations. This binding initiates the infection process, leading to the virus’s entry into the host cell.
Once the S1 subunit binds to ACE2, a host cell enzyme, TMPRSS2, activates by cleaving the Spike protein. This cleavage induces significant conformational changes in the S2 subunit, which then mediates the fusion of the viral membrane with the host cell membrane. This membrane fusion creates an entry pore, allowing the viral genetic material to enter the host cell’s cytoplasm.
Other Essential Structural Proteins
Beyond the prominent Spike protein, SARS-CoV-2 possesses two other major structural proteins embedded within its viral envelope: the Membrane (M) protein and the Envelope (E) protein. These proteins are crucial for the virus’s structural integrity and replication. The M protein is the most abundant structural protein on the viral surface and is considered a central organizer for coronavirus assembly.
The Membrane (M) protein plays a significant role in shaping the virion and is involved in the assembly of new viral particles. It forms mushroom-shaped dimers and can further assemble into higher-order oligomers, contributing to the curvature of the viral envelope. The M protein also mediates the recruitment of the nucleocapsid protein and viral RNA, which are crucial steps in forming new virions.
The Envelope (E) protein is the smallest of the major structural proteins found in the viral membrane. It contributes to various stages of the viral life cycle, including viral assembly, budding, and release from host cells. The E protein can form ion channels, also known as viroporins, which manipulate the internal environment of the cell to facilitate viral replication and egress.
The Viral Genome and Nucleocapsid
At its core, SARS-CoV-2 contains a single-stranded RNA genome. This RNA is positive-sense, meaning it can be directly translated into proteins by the host cell’s machinery upon entry. The genome is approximately 30,000 nucleotides long, making it one of the largest among RNA viruses.
The Nucleocapsid (N) protein tightly binds to and encapsulates this RNA genome, forming a coiled structure inside the viral envelope. This interaction is fundamental for packaging the viral genome into new virions and is crucial for the virus’s replication process.
The N protein is a multifunctional phosphoprotein with two globular RNA-binding modules, the N-terminal domain (NTD) and C-terminal domain (CTD), connected by an intrinsically disordered region. These domains allow the N protein to recognize and bind to RNA, forming dense protein-nucleic acid compartments that protect the genetic material and concentrate viral components for efficient replication.