Small-Molecule Anti-HIV-1 Agents Based on HIV-1 Capsid Proteins

Biomolecules. 2021 Feb 3;11(2):208. doi: 10.3390/biom11020208.


The capsid of human immunodeficiency virus type 1 (HIV-1) is a shell that encloses viral RNA and is highly conserved among many strains of the virus. It forms a conical structure by assembling oligomers of capsid (CA) proteins. CA dysfunction is expected to be an important target of suppression of HIV-1 replication, and it is important to understand a new mechanism that could lead to the CA dysfunction. A drug targeting CA however, has not been developed to date. Hydrophobic interactions between two CA molecules via Trp184/Met185 in CA were recently reported to be important for stabilization of the multimeric structure of CA. In the present study, a small molecule designed by in silico screening as a dipeptide mimic of Trp184 and Met185 in the interaction site, was synthesized and its significant anti-HIV-1 activity was confirmed. Structure activity relationship (SAR) studies of its derivatives were performed and provided results that are expected to be useful in the future design and development of novel anti-HIV agents targeting CA.

Keywords: anti-HIV; capsid; dipeptide mimic; in silico screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / pharmacology*
  • Binding Sites
  • Capsid / chemistry
  • Capsid Proteins / chemistry*
  • Chemistry, Pharmaceutical
  • Chromatography, High Pressure Liquid
  • Computer Simulation
  • Dimerization
  • Drug Design
  • HEK293 Cells
  • HIV-1 / metabolism*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Peptides / chemistry
  • Permeability
  • Stereoisomerism
  • Structure-Activity Relationship
  • Virus Replication / drug effects


  • Anti-HIV Agents
  • Capsid Proteins
  • Peptides