What Does COVID-19 Look Like Under a Microscope?

The SARS-CoV-2 virus is the infectious agent responsible for COVID-19. Understanding its physical characteristics was a foundational step for developing effective countermeasures. Scientists focused high-powered imaging tools on the virus to reveal its architecture and structure. This visual information explains how the virus interacts with and invades human cells. This examination details the size, shape, and surface machinery that define this microscopic threat.

Size and Morphology of SARS-CoV-2

The virus is an extremely small biological particle, far beyond the visualization capability of a standard light microscope. Its size is measured in nanometers (nm). The diameter of a single SARS-CoV-2 particle, or virion, typically falls within a range of 50 to 140 nm, often cited around 100 nm.

The virus is tiny compared to common bacteria, which can be thousands of nanometers in length. The overall shape of the SARS-CoV-2 particle is generally spherical. Electron microscopy images often show it to be somewhat pleomorphic, meaning it can exhibit slightly variable or oval shapes. This morphology is defined by a lipid membrane that encapsulates the genetic material.

The Defining Surface Structures

The most striking feature of the SARS-CoV-2 virion is the set of protein projections that cover its outer surface. These protrusions give the virus family its name, as they resemble the solar corona. The surface is built from four main structural proteins: Spike (S), Membrane (M), Envelope (E), and Nucleocapsid (N), with the first three embedded in the lipid envelope.

The Spike (S) protein is the most prominent structure, forming large, club-shaped trimers that project outward from the viral surface. These spikes serve as the mechanism for host cell attachment and entry. The Spike protein binds directly to the Angiotensin-Converting Enzyme 2 (ACE2) receptor found on the surface of human cells, particularly those in the respiratory tract.

The Spike protein consists of two functional subunits, S1 and S2, which facilitate infection. The S1 subunit contains the receptor-binding domain that latches onto the host cell receptor. The S2 subunit is responsible for fusing the viral envelope with the host cell membrane. Each spike extends approximately 20 nm from the surface, making them the defining visual feature.

The Envelope (E) and Membrane (M) proteins are essential for the virus’s physical integrity and assembly. The M protein is the most abundant structural protein and works with the E protein to determine the virion’s size and shape. These two proteins are also involved in managing the trafficking of the Spike protein during the assembly of new viral particles.

How Scientists Visualize the Virus

Due to the virus’s nanoscale dimensions, specialized imaging technologies far more powerful than conventional light microscopes are required for visualization. Electron microscopy techniques use a beam of electrons instead of light, allowing scientists to achieve the resolution needed to image structures at the molecular level. These techniques provide different perspectives on the virus, from its external topography to its internal components.

Transmission Electron Microscopy (TEM) was one of the first techniques used to visualize the virus’s overall morphology and internal structure. TEM works by sending an electron beam through a thin sample, creating a two-dimensional image that reveals the internal organization of the virion. Scanning Electron Microscopy (SEM), in contrast, scans a focused beam of electrons across the surface of a sample to create a three-dimensional-like image, which is excellent for illustrating the surface topography and the arrangement of the spikes.

A more advanced technique called Cryo-Electron Microscopy (Cryo-EM) provides near-atomic resolution images of the virus’s structural proteins. Cryo-EM involves flash-freezing the sample in a thin layer of ice, preserving the virus in a near-native state without chemical distortion. Cryo-Electron Tomography (Cryo-ET), a variation of Cryo-EM, takes multiple images from different angles to construct high-resolution three-dimensional models of the entire virion and its components. This capability allows for observing the virus’s molecular structures, such as the Spike protein, as it exists inside infected cells.