Inhibition of Herpes Simplex Virus Ribonucleotide Reductase by Synthetic Nonapeptides: A Potential Antiviral Therapy

Herpes simplex virus (HSV) types 1 and 2 are pathogenic DNA viruses that cause diverse diseases in humansl, perhaps best exemplified by genital herpes which is primarily due to HSV-2 infection. It has been estimated that more than 20 million people are affected with genital herpes in the United States alone and that about 300,000 new cases are reported each year. Since herpesvirus infections are eventually attenuated by the host immune system in otherwise normal persons, newborns and immunocompromised patients are particularly vulnerable to more severe forms of infections. HSV belongs to the family of human herpesviruses which also includes varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpesviruses 6 and 7 (HHV-6 and HHV-7). While these different viruses are responsible for a variety of different pathologies associated with their specific life cycles in different human tissues, they do have several key features in common. After primary infection, herpesviruses have the capability to establish latency2, which is defined as a state in which the viral genome is present in certain cells but infectious virus is not produced. These viruses can be reactivated from the latent state by various stimuli such as ultraviolet light, stress and fever to produce new infectious virus. With respect to herpesvirus infections, development of vaccines has, thus far, met with little success. Therefore, it is important to develop alternative antiherpetic agents for use in the treatment of herpesvirus-induced diseases.