Cervical cancer is the fourth most common cancer in women. In 2018, an estimated 0.5 million women were diagnosed with cervical cancer worldwide, and about 0.25 million people died from the disease, which is caused by infection with infectious agents such as Human papillomavirus (HPV). HPV is a DNA virus that has a double-layered capsid structure, in the form of L1 and L2.
There are two types of HPV based on their ability to initiate cancer, namely, high risk (HR) and low risk (LR). HR types such as HPV-16 are classified as the majority, and it can trigger cancer, especially in the genital area, namely the cervix. This study uses sample data from HPV-16 because about 99% of the virus is the primary agent causing cervical cancer according to previous studies.
HPV consists of 2 types of structural protein-coding genes called late (L) and early (E) for functional proteins. One of the E protein that plays a crucial role in the transformation of normal cells is E6. E6 affects the activity of p53 in cells by forming the E6-p53 complex, thus directing the complex to the degradation mechanism through the pathway proteasome. P53 plays a role in the cell cycle as a tumor suppressor and regulation checkpoint.
Previous studies have shown that black tea compounds have been identified to affect inhibitory against certain types of viral infections in vitro. However, the report has not been able to explain how the molecular mechanism of the complex compounds contained in black tea can act as an inhibitor of functional proteins or play a role in the replication process of the virus. In fact, in silico, research related to the screening of natural compounds that have potential as E6 inhibitors has been carried out.
But researchers have not previously confirmed the existence of E6 conserved areas and targeted them in drug design. The potential of the conserved region on E6 HPV-16 protein is the main focus because E6 has a specific binding region that is conserved to be used to interact with p53. The case of functional protein resistance due to mutations such as in HIV-1 that causes some drugs to cross-resistance, but the problem can be resolved quickly with the introduction of a new drug called tipranavir. The drug works by binding to a conserved region, a functional trigger protease activation so that the target protein cannot carry out its activity.
This study aims to identify the areas conserved functional in E6 HPV-16 from all black tea strains and chemical compounds that have the potential to become inhibitors through studies in silico. Thus, it can be candidates for preventing cervical cancer. In this study, it was explained that all the chemical compounds contained in black tea were able to act as E6 HPV-16 inhibitors through direct binding to the conserved functional areas used to interact with p53. The binding of these complex compounds can affect the biological activity of E6, and it is predicted that p53 will not be degraded because the binding area is inhibited by black tea compounds and has the potential to prevent cervical cancer.
Author: Viol Dhea Kharisma, Alexander Patera Nugraha Link: http://www.connectjournals.com/toc2.php?abstract=3180300H_2795A.pdf&&bookmark=CJ-033216&&issue_id=Supp-01%20&&yaer=2020
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