title: Helicase-primase as a target of new therapies for herpes simplex virus infections.
abstract: The seminal discovery of acyclovir 40 years ago heralded the modern era of truly selective antiviral therapies and this drug remains the therapy of choice for herpes simplex virus infections. Yet by modern standards, its antiviral activity is modest and new drugs against novel molecular targets such as the helicase-primase have the potential to improve clinical outcome, particularly in high-risk patients. A brief synopsis of current therapies for these infections and clinical need is provided to help provide an initial perspective. The function of the helicase-primase complex is then summarized and the development of new inhibitors of the helicase-primase complex, such as pritelivir and amenamevir, is discussed. We review their mechanism of action, propensity for drug resistance, and pharmacokinetic characteristics and discuss their potential to advance current therapeutic options. Strategies that include combinations of these inhibitors with acyclovir are also considered, as they will likely maximize clinical efficacy.
authors: Division of Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: S H
authors: SH
authors: James
authors: K B
authors: KB
authors: Larson
authors: E P
authors: EP
authors: Acosta
authors: M N
authors: MN
authors: Prichard
mesh_terms: D000212:Acyclovir / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004265:DNA Helicases / Q000037:antagonists & inhibitors; D019915:DNA Primase / Q000037:antagonists & inhibitors; D015195:Drug Design; D024882:Drug Resistance, Viral; D006561:Herpes Simplex / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D058990:Molecular Targeted Therapy; D010069:Oxadiazoles / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D014764:Viral Proteins / Q000037:antagonists & inhibitors
chemical_list: C568714:ASP2151; D000998:Antiviral Agents; D010069:Oxadiazoles; D011725:Pyridines; D013449:Sulfonamides; D013844:Thiazoles; D014764:Viral Proteins; C453221:pritelivir; D019915:DNA Primase; C062021:helicase-primase, Human herpesvirus 1; D004265:DNA Helicases; D000212:Acyclovir