New Insights Reveal Human Body's Defense Against COVID-19 Virus

Medical News: A new study by researchers from Mintek’s Biomedical Group in Randburg and the University of South Africa provides critical insights into how the human body naturally defends itself against the COVID-19 virus. The study team identified specific cellular mechanisms, known as restriction factors, that prevent the replication of SARS-CoV-2, the virus responsible for COVID-19. This Medical News report delves into the details of these mechanisms and highlights potential future treatments targeting these natural defenses.


An adaptive immune response to the first and second exposure to the SARS-CoV-2 antigen (S protein) is depicted in the diagram. Pattern recognition receptors (PRRs) to pathogen-associated molecular patterns (PAMPs) are the initial mechanism by which innate immunity functions. Strong antiviral type-I-interferon responses are elicited by antiviral innate membrane (TLR7, TLR8, and TLR9) or cytosolic related receptors (RIG-I-like receptors)

The Search for Host-Based Treatments
The study focused on understanding how the body’s innate immune system, which provides the first line of defense against infections, can restrict viral replication. The COVID-19 pandemic has led to unprecedented research into the biology of coronaviruses, emphasizing the need for treatments that go beyond traditional antiviral drugs. As vaccines are failing in controlling the virus, host-directed therapies that leverage the body’s natural defenses may offer another way to combat the virus.
 
How Does Our Body Block Viral Replication?
Host restriction factors are specific proteins that can prevent viruses from replicating within our cells. Because these factors are generally more stable than viral components and may work against multiple viruses, they have gained attention as promising targets for developing new antiviral treatments. Using advanced “omics” technologies, the research team mapped out how different host factors interfere with various stages of the SARS-CoV-2 life cycle.
 
The study sheds light on the body’s antiviral capabilities, highlighting key cellular mechanisms that obstruct SARS-CoV-2 replication. Through genetic and protein screening methods, researchers identified several proteins that play pivotal roles in blocking the virus from binding, entering cells, translating RNA, and forming new viral particles.
 
The Host Factors That Defend Against COVID-19
The researchers identified several human cellular restriction factors that prevent the SARS-CoV-2 virus from successfully replicating. Here’s a closer look at these essential defense mechanisms:
 
-LY6E (Lymphocyte Antigen 6 Complex Locus E): LY6E works as a surface protein that inhibits the fusion of viral and cellular membranes, blocking the virus from entering cells. This mechanism prevents SARS-CoV-2 from spreading between cells, slowing infection.
 
-CH25H (Cholesterol-25-Hydroxylase): This enzyme co nverts cholesterol into 25-hydroxycholesterol, a compound that reduces available cholesterol in the cell membrane. Since cholesterol is essential for viral entry, CH25H effectively prevents the SARS-CoV-2 virus from entering host cells.
 
-HD5 (Human Defensin 5): Produced by the body’s Paneth cells, HD5 binds to specific proteins on SARS-CoV-2, blocking the virus from attaching to cell receptors. This effectively prevents the virus from entering and infecting host cells.
 
-PSGL-1 (P-Selectin Glycoprotein Ligand-1): Normally involved in immune cell binding, PSGL-1 also obstructs viral entry. By attaching to virus particles, PSGL-1 prevents SARS-CoV-2 from binding to and infecting cells.
 
-TRIM28 (Tripartite Motif Containing 28): This protein plays a dual role as both a suppressor of viral infection and a regulator of cellular defense. It decreases the expression of the ACE2 receptor that SARS-CoV-2 uses to enter cells, effectively lowering the chance of infection.
 
-PLSCR1 (Phospholipid Scramblase 1): This protein selectively targets SARS-CoV-2 viral particles in the cell’s endosomes, blocking their escape into the cell’s interior and thus hindering the virus’s ability to replicate.
 
-SERINC5 (Serine Incorporator 5): SERINC5 integrates into the viral envelope and interferes with virus-cell membrane fusion, stopping the virus from releasing its genetic material into the host cell.
 
These factors highlight the innate immunity mechanisms our bodies use to counter SARS-CoV-2. By preventing viral entry and replication at multiple stages, these proteins could pave the way for therapies that enhance natural immunity against COVID-19.
 
Potential for New Host-Directed COVID-19 Therapies
Understanding how these restriction factors work opens up the possibility of developing drugs that can boost the body’s natural defenses. For example, a drug could be designed to increase LY6E or CH25H levels, making it harder for the virus to enter cells. Such approaches could complement existing COVID-19 treatments, especially for those who cannot receive vaccines or traditional antiviral medications.
 
Researchers also see potential in utilizing CRISPR-Cas9 technology to enhance the expression of these host factors in cells. This approach could lead to genetic modifications that strengthen our immune response and limit the virus’s ability to adapt. Using host-directed therapies could provide a broad-spectrum solution that not only works against SARS-CoV-2 but also against similar viruses that may cause future pandemics.
 
Why Host Factors Matter in the Fight Against COVID-19
While vaccines and antivirals directly target viruses, the body’s innate immunity offers a stable, universal defense that does not easily evolve resistance. Host restriction factors are less likely to lose effectiveness over time, making them reliable tools against a range of viral threats. As the COVID-19 pandemic has shown, the ability to quickly mobilize effective therapies is essential, and host-based approaches offer the potential for more flexible and broadly applicable treatments.
 
Conclusion: Moving Towards a Broader Defense Strategy
The discovery of human cellular restriction factors that inhibit SARS-CoV-2 replication highlights the power of our innate immune system in fighting infections. By focusing on these host factors, researchers are developing a new class of antiviral therapies that could provide an extra layer of protection against COVID-19 and future viral threats. Unlike traditional antivirals, these treatments target stable cellular mechanisms, potentially offering long-lasting effectiveness without the risk of viral resistance.
 
This research offers hope for a world better prepared for future pandemics, where treatment strategies are more resilient and less reliant on the specifics of each new virus. By understanding and enhancing our body’s natural defenses, we may have a powerful tool to protect public health against both known and emerging pathogens.
 
The study findings were published in the peer-reviewed journal: Frontiers in Virology.
https://www.frontiersin.org/journals/virology/articles/10.3389/fviro.2024.1462283/full
 
For the latest COVID-19 News, keep logging into Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/chinese-researchers-discover-host-protein-actn4-as-a-promising-new-target-in-the-fight-against-sars-cov-2
 
https://www.thailandmedical.news/news/ifitm-proteins-can-protect-against-viruses