Physicochemical and sequence determinants of antiviral peptides.

Abstract

Antiviral peptides (AVPs) open new possibilities as an effective antiviral therapeutic in the current scenario of evolving drug-resistant viruses. Knowledge about the sequence and structure activity relationship in AVPs is still largely unknown. AVPs and antimicrobial peptides (AMPs) share several common features but as they target different life forms (living organisms and viruses), exploring the differential sequence features may facilitate in designing specific AVPs. The current work developed accurate prediction models for discriminating (a) AVPs from AMPs, (b) Coronaviridae AVPs from other virus family specific AVPs and (c) highly active AVPs (HAA) from lowly active AVPs (LAA). Further explainable machine learning methods (using model agnostic global interpretable methods) are utilized for exploring and interpreting the physicochemical spaces of AVPs, Coronaviridae AVPs and highly active AVPs. To further understand the association of physicochemical space distribution with pIC50 values, regression models were developed and analyzed using accumulated local effects and interaction strength analysis. An independent sample t-test is used to filter out the significant compositional differences between the smaller length HAA and longer length HAA groups. AVPs prefer lower charge/length ratio and basic residues in comparison with AMPs. Coronaviridae family-specific AVPs have lower propensities for basic amino acids, charge and preference for aspartic acid. Further there is prevalence for basic residues in lowly active AVPs as compared to highly active AVPs. Sequence order effects captured in terms of average amino acid pair distances proved to be more constructive in deciphering the sequences of AVPs.