It is well known that 99.7% of cervical cancers are related to human papillomavirus (HPV) infection.
This virus is a large family, with over 100 known types of HPV viruses. Among them, HPV 16 and HPV 18 are the two most common high-risk types.
The frenzy for HPV vaccines has been ongoing for quite some time, with many people even taking advantage of overseas trips to get vaccinated abroad. After all, compared to getting vaccinated domestically, overseas vaccinations not only avoid the hassle of appointments but also ensure a constant supply.
However, this method is clearly not suitable for everyone. What about the young ladies who haven't received the injection and are past the prescribed age?
Although vaccines provide a reliable first line of defense against HPV infection, we also know that they are not 100% protective "weapons," have certain limitations, and there are currently no drugs specifically designed to inhibit HPV infection or transmission.
Therefore, many researchers are still searching for other ways to combat HPV.
Recently, researchers at Yale University discovered a method to directly block the spread of HPV and published an article in the Proceedings of the National Academy of Sciences (PNAS). Hey, are you excited?
Previously, no specific antiviral drug could suppress HPV infection. Therefore, based on the mechanism by which HPV enters cells, researchers utilized viral protein fragments that mediate infection, turning them into a drug capable of inhibiting the infection.
What exactly is the method?
Viral replication requires the interaction between viral proteins and cellular proteins. This interaction mediates many aspects of viral infection, including the transport of the viral genome into the cell.
First, we need to understand the mechanism of HPV infection.
HPV is a non-enveloped DNA virus that contains 360 main capsid protein molecules (L1) and 72 capsid protein molecules (L2). L2 is essential for viral transport to the cell nucleus, viral gene expression sites, and the site of DNA replication.
When infected with HPV, a cellular protein complex called the retromer binds to HPV capsid protein L2. The virus particles that enter are then sorted and transported into the retrograde transport pathway, eventually being transported to the cell nucleus.
In this study, researchers aimed to inhibit HPV infection by blocking this viral transport process. They synthesized a peptide containing 29 residues, named P16/16.
P 16/16 contains the retromer binding site (RBS) of HPV 16 capsid protein L2 and a cell-penetrating peptide (CCP) that can be delivered across the cell membrane.
They added P16/16 to the culture medium of uninfected human cervical cancer cells (HeLa cells) and found that these peptides, after entering the cytoplasm, bind to retromers. At this point, when HPV 16 pseudoviruses attempt to infect human cervical cancer cells, they can no longer bind to retromers, and the infection is blocked.
Evaluations have shown that P16/16 can also block HPV 16 virus infection. In addition to HPV 16, HPV 18 and HPV 5 can also be suppressed in this way.
Based on measurements of cell morphology and cell viability, researchers observed that the effective antiviral dose of P 16/16 did not show significant toxicity within 72 hours, meaning that this method is safe.
The researchers also tested whether removing the peptide from the culture medium before infection would eliminate the inhibitory effect. They pretreated the cells for 24 hours, removed P16/16 from the culture medium, and then attempted to infect the cells at different time points.
They found that 48 hours after removing P16/16, the cells still showed significant inhibitory effects on the virus, but the inhibitory effect was not significant compared to shortly after peptide removal.
This inhibitory effect lasted for at least 96 hours. Furthermore, even after P16/16 and HPV were removed from the culture medium after 24 hours, the infection did not recur for the next three days.
This indicates that the peptide has a sustained, and possibly irreversible, inhibitory effect on infection!
Because HPV infection is a localized infection of the skin and mucous membranes that requires direct contact with a carrier, short-term topical application of HPV inhibitors may help prevent genital HPV infection with minimal toxicity.
If we could create agents that can enter cells and disrupt the necessary interactions between proteins to inhibit viral replication, this approach would be applicable to many viruses other than HPV.
If it could actually be used, it would be fantastic news for humanity!
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