SARS-CoV-2, the virus that causes COVID-19, encodes at least four proteins that are known to contribute to disease severity: the spike (S) protein, the envelope (E) protein, the membrane (M) protein, and the nucleocapsid (N) protein.
The S protein is the most well-studied of these proteins and is responsible for the virus’s ability to attach to and enter human cells. However, the other proteins also play important roles in the virus’s life cycle and virulence.
The E protein is responsible for the formation of the viral envelope, which protects the viral genome from degradation. The M protein helps the viral envelope fuse with the cell membrane, allowing the virus to enter the cell. The N protein binds to the viral genome and is essential for its replication.
Studies in animal models have shown that all four of these proteins are required for full virulence of SARS-CoV-2. Mutations that reduce the function of any of these proteins can result in a less severe disease.
While the S protein is the most important determinant of disease severity, the other SARS-CoV-2 proteins also contribute to the severity of the disease.
SARS-CoV-2, the novel coronavirus that emerged in late 2019, encodes a suite of proteins that are critical for its infectivity. The best-characterized of these proteins is the spike (S) glycoprotein, which interacts with human ACE2 receptors to facilitate viral entry into target cells. However, other SARS-CoV-2 proteins are also important for disease severity and may help to explain why some infected individuals experience only mild symptoms, while others develop more severe disease.
Recent studies have shown that the viral nucleocapsid (N) protein, which plays a role in viral replication, may also contribute to disease severity. N protein has been shown to bind to human p53 proteins, which are important regulators of the cell cycle. This interaction leads to the accumulation of p53 in the nucleus, where it inhibits the transcription of genes that are important for cell proliferation. This may help to explain why cells infected with SARS-CoV-2 show decreased proliferation and may contribute to the development of severe symptoms in some patients.
The viral RNA-dependent RNA polymerase (RdRp) is another important SARS-CoV-2 protein that has been linked to disease severity. RdRp is necessary for viral replication and has been shown to bind to human proteins involved in the innate immune response, such as RIG-I and MDA5. This interaction leads to the production of pro-inflammatory cytokines, which may contribute to the development of severe respiratory disease in some patients.
Thus, while the SARS-CoV-2 spike protein is the best-characterized virulence factor, other viral proteins also play important roles in disease severity. These proteins may help to explain why some infected individuals experience more severe symptoms than others.