Interdiction of Protein Folding for Therapeutic Drug Development in SARS CoV-2
Fernando Bergasa-Caceres, Herschel Rabitz
Abstract
In this article, we predict the folding initiation events of the ribose phosphatase domain of protein Nsp3 and the receptor binding domain of the spike protein from the severe acute respiratory syndrome (SARS) coronavirus-2. The calculations employ the sequential collapse model and the crystal structures to identify the segments involved in the initial contact formation events of both viral proteins. The initial contact locations may provide good targets for therapeutic drug development. The proposed strategy is based on a drug binding to the contact location, thereby aiming to prevent protein folding. Peptides are suggested as a natural choice for such protein folding interdiction drugs.
Topics & Concepts
InterdictionProtein foldingCoronavirusDrugSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Drug developmentFolding (DSP implementation)Computational biologyPlasma protein bindingDrug discoveryCoronavirus disease 2019 (COVID-19)ChemistryBiologyCell biologyMedicineBiochemistryPharmacologyEngineeringDiseaseInfectious disease (medical specialty)PathologyElectrical engineeringAerospace engineeringSARS-CoV-2 and COVID-19 ResearchProtein Structure and DynamicsBacteriophages and microbial interactions