Abstract
The peptides derived from envelope proteins have been shown to inhibit the protein-protein interactions in the virus membrane fusion process and thus have a great potential to be developed into effective antiviral therapies. There are three types of envelope proteins each exhibiting distinct structure folds. Although the exact fusion mechanism remains elusive, it was suggested that the three classes of viral fusion proteins share a similar mechanism of membrane fusion. The common mechanism of action makes it possible to correlate the properties of self-derived peptide inhibitors with their activities. Here we developed a support vector machine model using sequence-based statistical scores of self-derived peptide inhibitors as input features to correlate with their activities. The model displayed 92% prediction accuracy with the Matthew’s correlation coefficient of 0.84, obviously superior to those using physicochemical properties and amino acid decomposition as input. The predictive support vector machine model for self- derived peptides of envelope proteins would be useful in development of antiviral peptide inhibitors targeting the virus fusion process.
Highlights
Fusion process is the initial step of viral infection, targeting the fusion process represents a promising strategy in design of antiviral therapy [1]
There are three classes of envelope proteins [2]: Class I E proteins include influenza virus (IFV) hemagglutinin and retrovirus Human Immunodeficiency Virus 1 (HIV-1) gp41; Class II E proteins include a number of important human flavivirus pathogens such as Dengue virus (DENV), Japanese encephalitis virus (JEV), Yellow fever virus (YFV), West Nile virus (WNV), hepatitis C virus (HCV) and Togaviridae virus such as alphavirus Semliki Forest virus
We developed three support vector machine (SVM) models using physicochemical properties, amino acid composition and statistical discriminative function as input features
Summary
Fusion process is the initial step of viral infection, targeting the fusion process represents a promising strategy in design of antiviral therapy [1]. The entry step involves fusion of the viral and the cellular receptor membranes, which is mediated by the viral envelope (E) proteins. Enfuvirtide (T20), a peptide that mimicks the HR2 region of Class I HIV-1 gp, is the first FDA-approved HIV-1 fusion drug that inhibits the entry process of virus infection [5,6,7]. Peptides derived from a distinct region of GB virus C E2 protein were found to interfere with the very early events of the HIV-1 replication cycle [10]. Other successful examples of Class I peptide inhibitors include peptide inhibitors derived from SARS-CoV spike glycoprotein [11,12,13] and from Pichinde virus (PICV) envelope protein [14]. A peptide derived from the fusion initiation region of the glycoprotein hemagglutinin (HA) in IFV, Flufirvitide-3 (FF-3) has progressed into clinical trial [15]
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