The COVID-19 pandemic has had a profound impact on global health and the economy. The emergence of new variants of the virus has made the outbreak more complex and challenging to control. To effectively combat the virus, it is crucial to understand how it enters host cells.
SARS-CoV-2 enters host cells by binding to a receptor called angiotensin-converting enzyme 2 (ACE2), which is found on the surface of certain cells. This binding initiates the infection process. The virus can enter cells through either the cell surface or endocytic pathways. In the cell surface pathway, the viral Spike protein is cleaved by enzymes, leading to membrane fusion and the release of viral RNA into the cell. In the endocytic pathway, the virus is internalized into the cell through endocytosis before further membrane fusion and RNA release.
Despite ACE2 being the primary receptor, there are discrepancies in its expression patterns compared to the virus’s tissue tropism. High levels of ACE2 are found in tissues like the small intestine, testis, kidney, heart muscle, and colon, while it is relatively low in the lungs, a major target organ for infection. This suggests that additional host factors may be involved in facilitating viral entry into certain cell types with low ACE2 expression.
Scientists from China Medical University and Academia Sinica in Taiwan have recently identified a host protein called ADAM9 as a critical factor in SARS-CoV-2 entry. ADAM9 is a transmembrane protein that binds directly to the Spike protein and can interact with ACE2. Silencing ADAM9 reduces virus entry, while its overexpression enhances infection. The enzymatic activity of ADAM9 also plays a role in facilitating virus entry.
The discovery of ADAM9 as a host factor offers new possibilities for the development of antiviral strategies against COVID-19. ADAM9 is widely expressed in human tissues and is upregulated in various cancers. Interestingly, higher ADAM9 expression levels have been found in critically ill COVID-19 patients, suggesting a potential link between ADAM9 expression and disease severity.
Cancer patients with elevated ADAM9 expression have been shown to have a higher risk of severe COVID-19 and increased mortality rates. This raises questions about the relationship between ADAM9 expression and COVID-19 severity. Further research is needed to explore the impact of ADAM9 knockout and its potential effects on viral entry.
In conclusion, the discovery of ADAM9’s role in facilitating SARS-CoV-2 entry provides valuable insights into the mechanisms of COVID-19 infection. It also highlights ADAM9 as a potential therapeutic target in the ongoing battle against the virus. Understanding the complex interactions between host factors and the virus is crucial for developing effective countermeasures in the face of evolving variants. Continued research in this field will deepen our understanding and contribute to innovative approaches to combat COVID-19.