Letermovir and inhibitors of the terminase complex: A promising new class of investigational antiviral drugs against human cytomegalovirus

Dante P. Melendez, Raymund R. Razonable

Research output: Contribution to journalReview article

42 Scopus citations

Abstract

Infection with cytomegalovirus is prevalent in immunosuppressed patients. In solid organ transplant and hematopoietic stem cell transplant recipients, cytomegalovirus infection is associated with high morbidity and preventable mortality. Prevention and treatment of cytomegalovirus with currently approved antiviral drugs is often associated with side effects that sometimes preclude their use. Moreover, cytomegalovirus has developed mutations that confer resistance to standard antiviral drugs. During the last decade, there have been calls to develop novel antiviral drugs that could provide better options for prevention and treatment of cytomegalovirus. Letermovir (AIC246) is a highly specific antiviral drug that is currently undergoing clinical development for the management of cytomegalovirus infection. It acts by inhibiting the viral terminase complex. Letermovir is highly potent in vitro and in vivo against cytomegalovirus. Because of a distinct mechanism of action, it does not exhibit cross-resistance with other antiviral drugs. It is predicted to be active against strains that are resistant to ganciclovir, foscarnet, and cidofovir. To date, early-phase clinical trials suggest a very low incidence of adverse effects. Herein, we present a comprehensive review on letermovir, from its postulated novel mechanism of action to the results of most recent clinical studies.

Original languageEnglish (US)
Pages (from-to)269-277
Number of pages9
JournalInfection and Drug Resistance
Volume8
DOIs
StatePublished - Aug 5 2015

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Keywords

  • AIC246
  • Antivirals
  • Cytomegalovirus
  • Letermovir
  • Terminase
  • Transplantation

ASJC Scopus subject areas

  • Pharmacology
  • Infectious Diseases
  • Pharmacology (medical)

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