Novel Binding Mechanisms of Fusion Broad Range Anti-Infective Protein Ricin A Chain Mutant-Pokeweed Antiviral Protein 1 (RTAM-PAP1) against SARS-CoV-2 Key Proteins in Silico

Toxins (Basel). 2020 Sep 17;12(9):602. doi: 10.3390/toxins12090602.

Abstract

The deadly pandemic named COVID-19, caused by a new coronavirus (SARS-CoV-2), emerged in 2019 and is still spreading globally at a dangerous pace. As of today, there are no proven vaccines, therapies, or even strategies to fight off this virus. Here, we describe the in silico docking results of a novel broad range anti-infective fusion protein RTAM-PAP1 against the various key proteins of SARS-CoV-2 using the latest protein-ligand docking software. RTAM-PAP1 was compared against the SARS-CoV-2 B38 antibody, ricin A chain, a pokeweed antiviral protein from leaves, and the lectin griffithsin using the special CoDockPP COVID-19 version. These experiments revealed novel binding mechanisms of RTAM-PAP1 with a high affinity to numerous SARS-CoV-2 key proteins. RTAM-PAP1 was further characterized in a preliminary toxicity study in mice and was found to be a potential therapeutic candidate. These findings might lead to the discovery of novel SARS-CoV-2 targets and therapeutic protein structures with outstanding functions.

Keywords: COVID-19; SARS-CoV-2; antiviral agent; fusion proteins; pokeweed antiviral protein; ribosome-inactivating proteins; ricin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / therapeutic use*
  • Betacoronavirus / drug effects*
  • COVID-19
  • Computer Simulation
  • Coronavirus Infections / drug therapy*
  • Humans
  • Mice
  • Models, Animal
  • Pandemics
  • Phytolacca americana / chemistry
  • Plant Leaves / chemistry
  • Pneumonia, Viral / drug therapy*
  • Protein Binding / drug effects*
  • Ribosome Inactivating Proteins, Type 1 / chemistry*
  • Ribosome Inactivating Proteins, Type 1 / genetics
  • Ribosome Inactivating Proteins, Type 1 / therapeutic use*
  • Ricin / therapeutic use*
  • SARS-CoV-2

Substances

  • Antiviral Agents
  • Ribosome Inactivating Proteins, Type 1
  • Ricin
  • pokeweed antiviral protein