Pathogenic Viruses

Over the course of human civilization, viral infections have caused millions of human casualties worldwide, driving the development of antiviral drugs in a pressing need [1, 2].

As of April 2016, antiviral drugs have been approved to treat 9 human infectious diseases:  HIV infections, hepatitis B (HBV), hepatitis C (HCV), human cytomegalovirus (HCMV), herpes simplex virus (HSV), human papillomavirus (HPV), respiratory syncytial virus (RSV), varicella-zoster virus (VZV), and influenza virus, albeit a definitive cure for most of them is yet to be discovered [3, 4]. Furthermore, there is still no antiviral drug or vaccine for over 200 human viruses afflicting populations worldwide [3].

The development of antiviral treatments remains a challenge due to the highly variable nature of virus genomes. Furthermore, the emerging drug resistance mutations remain a major cause of treatment failure, calling for a joint effort between scientific and industrial partners [4-8].

Viruses and cancer

Viruses account for ca. 20% of total human cancer cases. Although many viruses can cause tumors in animals, only seven of them are associated with human cancers and are considered oncogenic viruses: hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), Epstein Barr virus (EBV), human herpes virus 8 (HHV8), Merkel cell polyomavirus (MCPyV), and the human T-lymphotropic virus (HTLV-1). Both HBV and HCV cause around 80% of hepatocellular carcinoma (HCC), the most common cancer of the liver. High-risk HPV strains are the major causes of cervical cancer and other ano-genital neoplasms, head and neck tumors. EBV is associated with nasopharyngeal carcinoma, Hodgkin’s lymphoma, and Burkitt’s lymphoma. HHV8 (also called Kaposi’s sarcoma-associated herpesvirus, KSHV) is responsible for Kaposi’s sarcoma, often found in patients with immunodeficiency syndrome (AIDS). MCPyV causes Merkel cell carcinoma and HTLV-1 is the causative agent of adult T-cell lymphoma [9].

Recently, Herpes virus 6A (HHV-6A) and 7 (HHV-7) has been linked to Alzheimer’s disease [10].

Antiviral compounds with broad-spectrum activity against different virus genotypes or subtypes are in demand, because the effectiveness of most antiviral drugs is limited to only certain viral strains [8].

References

1.Clercq, E. D., Antivirals and antiviral strategies. Nat. Rev. Microbiol. 2004, 2, 704.
2.De Clercq, E., Strategies in the design of antiviral drugs. Nature Reviews Drug Discovery 2002, 1, 13.
3.Woolhouse, M.; Scott, F.; Hudson, Z.; Howey, R.; Chase-Topping, M., Human viruses: discovery and emergence. Philosophical Transactions of the Royal Society B: Biological Sciences 2012, 367, (1604), 2864-2871.
4.De Clercq, E.; Li, G., Approved Antiviral Drugs over the Past 50 Years. Clin. Microbiol. Rev. 2016, 29, (3), 695-747.
5.Li, G.; Piampongsant, S.; Faria, N. R.; Voet, A.; Pineda-Peña, A.-C.; Khouri, R.; Lemey, P.; Vandamme, A.-M.; Theys, K., An integrated map of HIV genome-wide variation from a population perspective. Retrovirology 2015, 12, (1), 18.
6.Li, G.; Verheyen, J.; Rhee, S.-Y.; Voet, A.; Vandamme, A.-M.; Theys, K., Functional conservation of HIV-1 Gag: implications for rational drug design. Retrovirology 2013, 10, (1), 126.
7.Boons, E.; Li, G.; Vanstreels, E.; Vercruysse, T.; Pannecouque, C.; Vandamme, A.-M.; Daelemans, D., A stably expressed llama single-domain intrabody targeting Rev displays broad-spectrum anti-HIV activity. Antivir. Res. 2014, 112, 91-102.
8.Li, G., HIV genome-wide diversity, interaction and coevolution. HIV genoom diversiteit, interactie en co-evolutie 2014.
9.Luo, G. G.; Ou, J.-h. J., Oncogenic viruses and cancer. Virol. Sin. 2015, 30, (2), 83-84.
10.Readhead, B.; Haure-Mirande, J.-V.; Funk, C. C.; Richards, M. A.; Shannon, P.; Haroutunian, V.; Sano, M.; Liang, W. S.; Beckmann, N. D.; Price, N. D.; Reiman, E. M.; Schadt, E. E.; Ehrlich, M. E.; Gandy, S.; Dudley, J. T., Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Neuron.