Mapping the HPV Virus Capsid Structure To Create More Effective Vaccines and Medications
New structural research on the human papillomavirus opens the door to the development better vaccines and antiviral therapies. Image Credit: AJ Cann
Over the past decade, the number of cancers associated with the human papillomavirus (HPV) has been on the rise, making infection an increasingly pressing public health issue.1 Currently, the Center for Disease Control and Prevention estimates that 80 million people in the United States, including one in every four women, is infected with the virus, and that it causes more than thirty thousand cancers in men and women each year. Most significantly, HPV is responsible for over 90 percent of cervical cancers in women, but it also causes oropharyngeal, anal, rectal and other reproductive system cancers in both men and women. HPV also causes genital warts, which, while more easily treatable than cancer, still weighs on the American healthcare system.2
In light of this concerning public health situation, researchers have been conducting studies to probe the structure of the virus, and in February 2017, structural biologists at Penn State College released the first-ever high-resolution cryo-EM structure of HPV. The 4.3-Angstrom three-dimensional structure reveals significant features of the viral capsid,3 which could be useful for the development of novel HPV vaccines and antiviral medications, as well as improve the way that research is done in the field. As biomedical scientists look to use the cryo-EM map for their research and development efforts, modern software can help increase lab efficiency and reduce the failure rate of candidate drugs.
New Findings on HPV Structure
The cryo-EM map released by the research group at Penn State College reveals a variety of previously unknown features of the capsid of the most prevalent strain of the human papillomavirus (HPV-16). For instance, they showed that the major structural protein that makes up the capsid, termed L1, is arranged asymmetrically. In addition, they discovered that there are fewer minor structural proteins (L2) than previously believed, and that L2 plays a key role in the binding of the virus to target cells. This information can help drug developers better understand how the virus works, and also develop more accurate ways to study the virus.4 Consider the following applications of this research:
- Novel Vaccines for HPV
The existing vaccines against human papillomavirus are genotype-specific, which means that they only protect against certain strains of the virus.5 However, L2 proteins are known to be conserved across HPV genotypes, so a better understanding of their structural features can lead to the development of a more comprehensive vaccine. This would not only make the vaccine more beneficial to young people who receive the vaccine before they become sexually active, but it could also increase the feasibility of vaccinating people past their mid-20’s. Currently, the FDA has only approved the HPV vaccine for females aged 11 to 26 and males aged 11 to 21, assuming that most people over that age will have already been exposed to the virus.6 But if the new vaccine covers more strains, it could have a beneficial effect for people in their thirties or even forties, who could be protected against less common strains to which they might not yet have been exposed.
- Antiviral Medications for Infected Patients
Right now, there are no antiviral medications for individuals who have already been infected by HPV. As a result, they can treat symptoms such as genital warts, but there is no way to temper their increased risk of cancer, especially cervical cancer in women: their only option is to get screened regularly and try to catch the cancer early. Plus, infected individuals will expose any future sexual partners to the strain of the virus with which they have been infected and propagate the rapid spread of HPV. Therefore, using the new structural information about HPV to develop an antiviral medication for people who are infected with HPV could significantly improve this public health situation.
- Improved Approaches to HPV Research
Of course, any drug development effort will require additional research in the lab, beyond cryo-EM structural studies. Because HPV itself is difficult to culture in a lab setting, researchers currently use three different stand-ins that are comprised of L1 and/or L2 proteins. However, the three different strains respond differently when exposed to antibodies or host cell receptors, which limits the applicability of research results. With a better understanding of capsid structure, it may be possible to develop a more reliable stand-in to use for wet lab HPV experiments.
Because HPV is a significant—and growing—public health problem, developing more comprehensive vaccines and novel antiviral medications could have a major effect on the lives of millions of people. It would also open a wide market for pharmaceutical companies, since HPV affects such a large proportion of the population in the United States. To reach this goal, researchers are turning to advanced software that supports virtual drug design and more effective analysis and interpretation of data. This can improve the quality of results, making it much less likely that a candidate pharmaceutical will fail in clinical trials, so exploration of new vaccines and antivirals against HPV could be even more promising.
BIOVIA Designed to Cure is an advanced software solution that can improve research processes and facilitate collaborative efforts in order to increase lab efficiency, enabling pharmaceutical companies to bring novel therapeutics to market more quickly than ever. Contact us today to learn more about how this software and our other offerings can help your organization find ways to address critical public health issues like HPV infection.
- “HPV-Associated Cancers on Rise in US,” July 7, 2016, http://www.medscape.com/viewarticle/865830 ↩
- “HPV vaccine: the underused cancer-prevention vaccine,” February 14, 2017, http://www.dallasnews.com/news/debunked/2017/02/14/cancer-preventing-vaccine-underused ↩
- “Cryoeletron Microscopy Maps of Human Papillomavirus 16 Reveal L2 Densities and Heparin Binding Site,” February 7, 2017, http://www.cell.com/structure/abstract/S0969-2126(16)30391-4 ↩
- “Scientists get best view yet of cancer-causing virus HPV,” January 23, 2017, https://pennstatehealthnews.org/2017/01/scientists-get-best-view-yet-of-cancer-causing-virus-hpv/?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+penn-state-college-of-medicine+%28Penn+State+College+of+Medicine%29 ↩
- Human Papillomavirus (HPV) Vaccines,” November 2, 2016, https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-vaccine-fact-sheet ↩
- “Left Out: Why Is It So Hard For Older Women to Get the HPV Vaccine?” June 18,2012, https://www.theatlantic.com/health/archive/2012/06/left-out-why-is-it-so-hard-for-older-women-to-get-the-hpv-vaccine/258611/ ↩