The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has brought the scientific community together in a race to understand the virus and develop effective therapeutic strategies. One key aspect of this research involves identifying the molecules that are essential for viral entry and infection. In a recent research article published in the Reviews in Medical Virology journal, Siti Fathiah Masre, Nurul Farhana Jufri, Farah Wahida Ibrahim, and Sayyidi Hamzi Abdul Raub explore the classical and alternative receptors for SARS-CoV-2 and discuss their roles in viral infection and dissemination.
What are the main entry molecules for SARS-CoV-2?
Through extensive research, it has been established that angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2) play crucial roles as the main entry molecules for SARS-CoV-2. These molecules facilitate the initial binding and entry of the virus into the host cells. ACE2, a membrane-bound enzyme, acts as the primary receptor for SARS-CoV-2. It is widely expressed in various organs and tissues, including the lungs, heart, kidneys, and gastrointestinal system.
TMPRSS2, on the other hand, is a protease enzyme responsible for priming the viral spike protein, which is essential for the fusion of the viral membrane with the host cell membrane. The activation of spike protein by TMPRSS2 facilitates efficient viral entry and subsequent infection. TMPRSS2 is expressed in the respiratory epithelium, making it a critical component in the early stages of SARS-CoV-2 infection.
What are the roles of these molecules in viral infection and dissemination?
ACE2 and TMPRSS2 play crucial roles in different stages of viral infection and dissemination. The initial interaction between the SARS-CoV-2 spike protein and ACE2 receptor enables viral attachment to host cells. This interaction is the first step in viral entry, allowing the virus to gain access to the host’s cellular machinery and establish infection.
TMPRSS2, as a protease, primes the spike protein by cleaving it and activating it for fusion with the host cell membrane. This process is essential for the virus to enter the host cell and release its genetic material, subsequently hijacking the host cell’s machinery for replication and viral protein production. TMPRSS2-mediated activation of the spike protein enables efficient viral entry and contributes to the pathogenesis of COVID-19.
The roles of ACE2 and TMPRSS2 extend beyond viral entry. ACE2 also plays a role in regulating the renin-angiotensin-aldosterone system (RAAS), which is involved in blood pressure regulation. The interaction between SARS-CoV-2 and ACE2 may disrupt the normal physiological functions of ACE2, leading to dysregulation of the RAAS and contributing to the systemic manifestations of COVID-19.
What are the other viral receptors and cellular proteases that are important for viral entry and transmission?
While ACE2 and TMPRSS2 are considered the main entry molecules for SARS-CoV-2, recent studies have shed light on several other viral receptors and cellular proteases that are also important in facilitating viral entry and transmission.
One such receptor is neuropilin-1 (NRP-1), which has been identified as an additional binding site for the SARS-CoV-2 spike protein. NRP-1 is widely expressed in various tissues, including the respiratory tract, and its interaction with the viral spike protein enhances viral infectivity. Blocking NRP-1 has shown promising results in reducing viral replication and infectivity, making it a potential therapeutic target for COVID-19.
Cellular proteases, such as cathepsin L and furin, have also been implicated in SARS-CoV-2 entry and replication. These proteases cleave the spike protein at different sites, triggering its activation and facilitating viral fusion with the host cell membrane. Inhibiting these proteases has shown to reduce viral infectivity in cell culture models, highlighting their potential as targets for antiviral therapies.
Implications of the research
This research article provides valuable insights into the molecular mechanisms underlying SARS-CoV-2 infection and dissemination. Understanding the entry molecules and their roles in viral infection can aid in the development of targeted therapeutic strategies.
One potential implication of this research is the identification of alternative receptors and proteases that can serve as targets for antiviral therapies. By targeting multiple entry points and inhibiting the interaction between the virus and host cells, it may be possible to develop more effective treatments for COVID-19.
The identification of neuropilin-1 as an additional receptor for SARS-CoV-2 opens up new avenues for drug development. Targeting NRP-1 could potentially limit viral infectivity and reduce the severity of COVID-19. Similarly, targeting cellular proteases like cathepsin L and furin could disrupt viral entry and replication, offering another potential therapeutic approach.
Overall, this research highlights the complexity of viral entry and the importance of considering multiple receptors and proteases in developing effective therapeutic strategies. By targeting these molecules, researchers and clinicians can work towards preventing viral infection, reducing transmission, and ultimately controlling the spread of COVID-19.
Source article: Classical and alternative receptors for SARS-CoV-2 therapeutic strategy – Masre – 2021
Disclaimer: While I have a passion for health, I am not a medical doctor and this is not medical advice.
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