SARS-CoV-2 mutations strengthen RBD-ACE2 binding, making the virus more infectious (2024)

FAQs

How does SARS-CoV-2 bind to ACE2? ›

SARS-CoV-2 and ACE2

For both SARS-CoV and SARS-CoV-2, the receptor-binding domain (RBD) of the S1 region is necessary for the binding of these virions to ACE2, thereby contributing to the ability of these particles to cause host cell infection.

Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity.

Wrapp et al. (Science2020, 367, 1260–1263) showed that the spike protein of SARS-CoV-2 binds to the ACE2 peptidase domain (ACE2-PD) more strongly than does SARS-CoV, and this fact may be associated with a greater severity of the new virus.

As a virus replicates, its genes undergo random “copying errors” (i.e. genetic mutations). Over time, these genetic copying errors can, among other changes to the virus, lead to alterations in the virus' surface proteins or antigens. Our immune system uses these antigens to recognize and fight the virus.

SARS-CoV-2 infects cells by attaching its spike proteins to ACE2 proteins that lie on the surface of the cells. Researchers are developing a “decoy” ACE2 to prevent SARS-CoV-2 from attaching to cells. SARS-CoV-2 infects cells by attaching its spike proteins to ACE2 proteins that lie on the surface of the cells.

ACE cleaves vasodilator angiotensin I into angiotensin II. ACE2 is also responsible for cleaving several peptide hormones. The most important being the removal of carboxyl-terminal amino acid phenylalanine from vasoconstricting angiotensin II and hydrolyses it back into angiotensin.

Virus mutation happens quickly over weeks to months due to the high number of viruses and infected people. Since it was first discovered, SARS-CoV2 has been acquiring two mutations in its genome (complete set of DNA) every two weeks.

SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions. Structure and dynamics of the SARS-CoV-2 envelope protein monomer. Surface Proteins of SARS-CoV-2 Drive Airway Epithelial Cells to Induce IFN-Dependent Inflammation.

Like other coronaviruses, the genome of SARS-CoV-2 is composed of a single strand of RNA with a positive strand (ready for translation and consequent synthesis of its proteins).

SARS-CoV-2 enters into a host cell by binding angiotensin-converting enzyme 2 (ACE2) on the cell surface, a process that can be facilitated by transmembrane protease serine 2 (TMPRSS2), which provides proteolytic cleavage of the viral spike (S) protein to promote virus–host fusion.

What virus does SARS-CoV-2 share the most genomic similarities? ›

In summary, SARS-CoV-2 shares a high degree of genomic similarity between other beta coronaviruses, including human SARS-CoV and bat SARS-like-CoVs/RaTG13.

SARS-CoV-2 is thought to have virulence factors directed against host immune responses. Current data suggests that the SARS-CoV-2 tricks the host into a delayed hyperactive innate immune response, leading to the cytokine storm commonly seen in severe COVID-19 cases.

The mutations that include deletion mutants were associated with 1252 of the 1273 residue positions and correspond to 6129 different mutation types. Besides, there were sequences also comprising insertion mutations. A single SARS-CoV-2 spike protein comprised anywhere between 1 and 55 mutations.

The virus that causes a respiratory disease called coronavirus disease 19 (COVID-19). SARS-CoV-2 is a member of a large family of viruses called coronaviruses. These viruses can infect people and some animals. SARS-CoV-2 was first known to infect people in 2019.

Two new receptors that specifically bind S protein of SARS-CoV-2 have recently been identified [73]. These proteins are ASGR1 (asialoglycoprotein receptor-1) and KREMEN1 (Kringle Containing Transmembrane Protein 1).

Binding of SARS-CoV-2 to the host cell receptor. SARS-CoV-2 S protein binds to the ACE2 receptor at the surface of host cells, initially through the S1 RBD. S1 is then shed from the viral surface, allowing S2 to fuse to the host cell membrane.

Previous studies have pointed out that sACE2 plays a role in the pathology of the disease, but the underlying mechanism is not yet clear. Recent studies have confirmed that sACE2 can also act as the receptor of SARS-COV-2, mediating viral entry into the cell and then spreading to the infective area.

Inhibiting ACE-2 glycosylation has shown to significantly reduce the infection of host cells by SARS-CoV-2 in a laboratory. This is the process by which chloroquine, hydroxychloroquine, and serine protease inhibitors are thought to work.