Morphology and Crystal Structure of SARS-CoV-2
The 2019 new coronavirus (2019-nCoV) is a kind of spherical, protruding surface, which looks like a crown under the electron microscope. The viral gene is a continuous linear single-stranded RNA with a diameter of 75–160nm. 2019-nCoV is the seventh member of the Coronaviridae family that has been discovered to infect humans. The other 6 members are: HCoV 229E, HCoV NL63, HCoV OC43, HCoV HKU1, SARS-CoV and MERS-CoV. 2019-nCoV belongs to β-coronavirus as well as SARS-CoV and MERS-CoV.
On February 12, 2020, the International Committee on Taxonomy of Viruses (ICTV) issued a statement officially renaming the 2019-nCoV to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is also recognized that this virus is the sister virus of SARS coronavirus, which indicates that the new coronavirus is a close relative of SARS coronavirus (SARS-CoV) from a taxonomic point of view.
On February 11, 2020, the world The World Health Organization (WHO) announced that it will name the new coronavirus pneumonia “COVID-19”: the letter CO stands for “corona”, the letter VI stands for “virus”, and the letter D stands for “disease” “(Disease), the number 19 indicates that the disease was discovered in 2019.
Morphology of SARS-CoV-2
Negative staining was used to observe the virus under an electron microscope. Viruses are generally spherical and some are polymorphic, with a diameter between 75–160nm. The edges of the virus particles have protrusions similar to the corona, about 9–12nm, and look like a crown. Extracellular free virus particles and inclusion bodies filled with virus particles in the cytoplasmic membrane sac were found in ultrathin sections of human airway epithelium. This morphology was consistent with the Coronaviridae.
Crystal structure of SARS-CoV-2
On January 16, 2020, the high-rate crystal structure of the new coronavirus 3CL hydrolase determined by the Rao Zihe/Yang Haitao research group of Shanghai University of Science and Technology was announced to the public.
3CL hydrolase (Mpro) is encoded by ORF1 (located at nsp5), located in the central region of the replicase gene, and is a key protein in the replication of new coronavirus RNA.
Mechanism of 3CL hydrolase action
The active form of the 3CL hydrolase molecule is a dimer formed by two homologous monomers, which are composed of the N-terminal heptapeptide SGFRKMA (N-finger), three domains (Domain I, II, III) and the connecting structure loop of domain II and domain III.
Domains I and II are β-sheets, and the enzyme active center is located in the gap between domains I and II. The interaction between the two monomer domains III to further stabilize the dimer structure of 3CL hydrolase. The N-terminal heptapeptides of the two monomers are inserted into the grooves of the domain II of each other, and the molecular conformation of the active center of the 3CL hydrolase is stably maintained by hydrogen bonding and salt bonding. The mature 3CL hydrolase can catalyze and hydrolyze 11 conserved sites of the replicator precursor polyprotein downstream of it, producing 13 end products of hydrolysis, as well as multiple intermediate products. These include the two most conserved regions of replicase, RNA polymerase and RNA helicase, which are necessary for viral RNA replication.
If the function of 3CL hydrolase is inhibited, the replication of viruses can be blocked with a high probability, indicating the direction for the development of antiviral drugs.
Atomic diagram of SARS-CoV-2
A new study published in the journal Science by the research team of the University of Texas at Austin and the National Institutes of Health on February 19, 2020 pointed out that they created the first 3D atom of the new coronavirus to attach and infect parts of human cells Scale structure diagram, which is a key step in developing vaccines and treatment methods.
Mechanism of SARS-CoV-2 invading human body
The new coronavirus uses highly glycosylated homotrimeric S protein to enter the host cell. The S protein undergoes many structural rearrangements to fuse the virus into the cell membrane of the host cell. This process involves the binding of the viral S1 subunit to the host cell receptor, triggering trimer instability, which in turn causes the S1 subunit to fall off the S2 subunit to form a highly stable post-fusion structure.
In order to access the host cell receptor, the receptor binding domain (RBD) in the S1 subunit undergoes a hinge-like conformational movement to hide or expose key sites for receptor binding. In this process, there are two states of S1: the “down” structure represents the receptor unbound state, and the “up” structure represents the receptor bindable state, but at the same time the “up” structure is relatively unstable.
Based on the published genome sequence, the research team carried out in vitro protein purification by affinity chromatography and gel exclusion chromatography, and then used cold electron microscopy technology to initially screen the new coronavirus S protein images showing high particle density. After 3D reconstruction, a spike protein (S protein) trimer structure with a resolution of 3.5 Å was finally obtained.
The research team has also sent the spine protein molecular structure map to the international database, waiting for publication, hoping that other teams will use their results to develop a vaccine as soon as possible.