Evitar

Evitar pre-designs siRNAs and CRISPR Cas13a guide RNAs from existing viral sequence data to enable pre-emptive antiviral therapeutic development against emerging RNA viruses.

Key Features:

• Pre-Design of siRNAs/Cas13a gRNAs: Utilizes sequences from existing viral strains to generate candidate siRNAs and Cas13a guide RNAs targeting viral genomes.
• Algorithmic Innovations: Implements the Greedy Algorithm with Redundancy and the Similarity-weighted Greedy Algorithm with Redundancy to optimize candidate selection and variant coverage.
• Time-Simulation Validation: Performs time-simulation analyses using historical coronavirus genomes, including identification of SARS-CoV-2-targeting sequences from data available as early as 2011.
• Broad Viral Applicability: Applied to multiple RNA viruses, including SARS-CoV-2, MERS-CoV, and the 2009-H1N1 influenza A virus.
• Experimental Validation: Includes designed siRNAs that were validated in vitro using reporter assays to demonstrate suppression of SARS-CoV-2 sequences.

Scientific Applications:

• Pre-designed therapeutic repository: Provides a collection of approximately 30 pre-designed, safety-tested siRNA and CRISPR therapeutic candidates to expedite outbreak response.
• Anticipatory target identification: Identifies candidate targeting sequences from historical viral sequence data to anticipate emergent viral threats.
• Cross-virus therapeutic design: Supports design and selection of RNA-targeting therapeutics for diverse RNA viruses, including coronaviruses and H1N1 influenza A.
• Experimental prioritization: Prioritizes candidates for in vitro reporter assay validation to confirm target suppression.

Methodology:

Evitar uses existing viral sequence data to design siRNAs and CRISPR Cas13a gRNAs, applies the Greedy Algorithm with Redundancy and the Similarity-weighted Greedy Algorithm with Redundancy, and conducts time-simulation analyses using historical coronavirus genome deposits.