KSHV-specific antivirals targeting the protein-DNA interaction of the latency-associated nuclear antigen

Future Med Chem. 2021 Jul;13(13):1141-1151. doi: 10.4155/fmc-2021-0059. Epub 2021 May 26.

Abstract

The Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic human herpesviruses that is responsible for cancer, especially in immunosuppressed people, such as patients with AIDS. So far, there are no KSHV-specifc antiviral agents available. In this review, we provide an overview on one particular target-centered approach toward novel anti-KSHV drugs focusing on interfering with the molecular functions of the latency-associated nuclear antigen (LANA). This review focuses on attempts to interfere with the LANA-DNA interaction mediated by the C-terminal domain. We describe the drug discovery approaches chosen for this endeavor as well as molecular structures that were identified in this innovative concept toward novel and KSHV-specific antiherpesviral agents.

Keywords: KSHV; LANA; antiherpesviral agents; latent infection; protein–DNA interactions; viral persistence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • DNA, Viral / drug effects*
  • Herpesvirus 8, Human / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Nuclear Proteins / antagonists & inhibitors*

Substances

  • Antigens, Viral
  • Antiviral Agents
  • DNA, Viral
  • Nuclear Proteins
  • latency-associated nuclear antigen