21 February 2014

Human papillomavirus: not only vaccination, but also treatment?

How to suppress the reproduction of the human papillomavirus

ChemPort.Ru based on the materials of Chemistry World: Small molecules stop cervical cancer virus assembling

Researchers from China managed to interrupt the life cycle of the virus, which is the main cause of cervical cancer – human papillomavirus, with the help of a low-molecular compound called "pillarene" (pillarene). The researchers hope that the results of their work will allow them to develop new ways to combat this virus.

Pillaren, designated CP5A, is the sodium salt of carboxypillar[5]arene. This compound is characterized by a strong cavity that can bind to amino acid residues.

Currently, about a hundred varieties of human papillomavirus (HPV) are known, 40 of which can be transmitted sexually. Most of the infections caused by these viruses occur without symptoms and do not lead to disease. However, there are a small number of types of this virus that can cause significant changes in cells, leading in some cases to the development of cervical cancer or laryngeal cancer. It is known that human papillomavirus types 16 and 18 are the cause of about 70% of reported cases of cervical cancer.

A number of countries have launched vaccination programs for adolescent girls against types 16 and 18 of the human papillomavirus. Nevertheless, according to the head of the pillar project, Qing-Wei Yang from Ying-Wei Yang from Qilin University, there is a need to develop alternative methods to combat HPV - existing vaccines are specific to the type of virus, must be transported in a cold chain mode (this is a smoothly functioning system providing an optimal temperature regime for the storage and transportation of medicines), which is not always possible to implement in developing countries, in which, we note, the incidence of cervical cancer is the highest.

The envelope of the human papillomavirus consists of two proteins – L1 and L2. They self-organize into pentamers that contribute to the fixation of the virus on cells and infection. A number of researchers are confident that disrupting the process of virus self-organization with the help of a low-molecular compound capable of contacting both proteins at once can stop the spread of the virus through the body.

Researchers from Yang's group studied a pillaren derivative, designated CP5A. The choice was due to the fact that CP5A is characterized by good solubility in water, and also demonstrates selective binding to the main proteinogenic amino acids L-lysine, L-arginine and L-histidine. These properties allow CP5A to bind to the amino acid residues of the L1 protein, preventing the formation of a pentamer and, accordingly, the self-assembly of virus particles.

Researchers from Qilin University hope to screen other low molecular weight compounds to find more specific inhibitors for more specific fragments at the interface of L1 and L2 proteins. The strategic goal of Chinese scientists is to develop a low–molecular compound for the treatment of HPV infection.

Margaret Stanley, an expert on the life cycle of the human papillomavirus from the University of Cambridge, finds the results of the new study important for understanding the features of the self-organization of the virus, but states that at the moment the significance of the new approach for therapy remains vague. According to Stanley, inhibiting the assembly of the virus can significantly block its reproduction, but this effect will not affect the genome of the virus, and it will be able to reactivate shortly after the end of the pillaren inhibitors course.

Article by Dong-Dong Zheng et al. Effective inhibition of human papillomavirus 16 L1 pentamer formation by a carboxylatopillarene and a p-sulfonatocalixarene is published in the journal Chemical Communications.

Portal "Eternal youth" http://vechnayamolodost.ru21.02.2014

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