Antiviral Agents as Therapeutic Strategies Against Cytomegalovirus Infections

Viruses. 2019 Dec 23;12(1):21. doi: 10.3390/v12010021.

Abstract

Cytomegalovirus (CMV) is a threat to human health in the world, particularly for immunologically weak patients. CMV may cause opportunistic infections, congenital infections and central nervous system infections. CMV infections are difficult to treat due to their specific life cycles, mutation, and latency characteristic. Despite recent advances, current drugs used for treating active CMV infections are limited in their efficacy, and the eradication of latent infections is impossible. Current antiviral agents which target the UL54 DNA polymerase are restricted because of nephrotoxicity and viral resistance. CMV also cannot be prevented or eliminated with a vaccine. Fortunately, letermovir which targets the human CMV (HCMV) terminase complex has been recently approved to treat CMV infections in humans. The growing point is developing antiviral agents against both lytically and latently infected cells. The nucleic acid-based therapeutic approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) are being explored to remove acute and/or latent CMV infections. HCMV vaccine is being developed for prophylaxis. Additionally, adoptive T cell therapy (ACT) has been experimentally used to combate drug-resistant and recurrent CMV in patients after cell and/or organ transplantation. Developing antiviral agents is promising in this area to obtain fruitful outcomes and to have a great impact on humans for the therapy of CMV infections.

Keywords: HCMV vaccine; acute/latent infection; adoptive cell therapy; antiviral agent; congenital infection; cytomegalovirus; nucleic acid-based therapeutic approach; therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiviral Agents / therapeutic use*
  • CRISPR-Cas Systems
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / complications
  • Cytomegalovirus Infections / drug therapy*
  • Cytomegalovirus Infections / therapy
  • Drug Resistance, Viral*
  • Humans
  • Immunotherapy, Adoptive
  • Viral Vaccines
  • Virus Latency / drug effects*

Substances

  • Antiviral Agents
  • Viral Vaccines