Protein Folding Interdiction Strategy for Therapeutic Drug Development in Viral Diseases: Ebola VP40 and Influenza A M1

Int J Mol Sci. 2022 Mar 31;23(7):3906. doi: 10.3390/ijms23073906.

Abstract

In a recent paper, we proposed the folding interdiction target region (FITR) strategy for therapeutic drug design in SARS-CoV-2. This paper expands the application of the FITR strategy by proposing therapeutic drug design approaches against Ebola virus disease and influenza A. We predict target regions for folding interdicting drugs on correspondingly relevant structural proteins of both pathogenic viruses: VP40 of Ebola, and matrix protein M1 of influenza A. Identification of the protein targets employs the sequential collapse model (SCM) for protein folding. It is explained that the model predicts natural peptide candidates in each case from which to start the search for therapeutic drugs. The paper also discusses how these predictions could be tested, as well as some challenges likely to be found when designing effective therapeutic drugs from the proposed peptide candidates. The FITR strategy opens a potential new avenue for the design of therapeutic drugs that promises to be effective against infectious diseases.

Keywords: Ebola; drug; folding; influenza; interdiction; pathway; therapeutic.

MeSH terms

  • COVID-19*
  • Drug Development
  • Ebolavirus* / metabolism
  • Hemorrhagic Fever, Ebola* / drug therapy
  • Humans
  • Influenza, Human* / drug therapy
  • Protein Folding
  • SARS-CoV-2
  • Viral Matrix Proteins / metabolism

Substances

  • M1 protein, Influenza A virus
  • VP40 protein, virus
  • Viral Matrix Proteins