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.

Yasser Hassan,Hui Ge,Sherry Ogg

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.

Highlights

A new global pandemic disease named COVID-19 has emerged and is still spreading at alarming rates at the time of this report
The three-dimensional (3D) structure of RTAM-PAP1 prediction was obtained as previously described [7], and those of RTA, PAP1, B38, and GRFT were retrieved in protein data bank (PDB) format from the Research Collaboratory for Structural Bioinformatics (RCSB) website
An additional run was conducted for ACE2 and human SARS-CoV antibody CR3022 against S1 receptor-binding domain (RBD) as a reference [5]

Summary

Introduction

A new global pandemic disease named COVID-19 has emerged and is still spreading at alarming rates at the time of this report. COVID-19 can cause severe symptoms such as damaging inflammatory response, fever, or severe respiratory illness and lead to death. The causative agent of COVID-19 was found to be a novel coronavirus closely related to the severe acute respiratory syndrome coronavirus (SARS-CoV) based on the latest phylogenetic analysis [1,2,3]. There are some major essential differences in their genetic makeup that led to their different behaviors. We still lack an effective antiviral strategy, drug, or vaccine to fight this virus, with the growing fear that SARS-COV-2 may become another endemic virus in our communities

Methods

Results

Conclusion