SMRI: A New Method for siRNA Design for COVID-19 Therapy.

Unlabelled: First discovered in Wuhan, China, SARS-CoV-2 is a highly pathogenic novel coronavirus, which rapidly spread globally and became a pandemic with no vaccine and limited distinctive clinical drugs available till March 13th, 2020. Ribonucleic Acid interference (RNAi) technology, a gene-silencing technology that targets mRNA, can cause damage to RNA viruses effectively. Here, we report a new efficient small interfering RNA (siRNA) design method named Simple Multiple Rules Intelligent Method (SMRI) to propose a new solution of the treatment of COVID-19. To be specific, this study proposes a new model named Base Preference and Thermodynamic Characteristic model (BPTC model) indicating the siRNA silencing efficiency and a new index named siRNA Extended Rules index (SER index) based on the BPTC model to screen high-efficiency siRNAs and filter out the siRNAs that are difficult to take effect or synthesize as a part of the SMRI method, which is more robust and efficient than the traditional statistical indicators under the same circumstances. Besides, to silence the spike protein of SARS-CoV-2 to invade cells, this study further puts forward the SMRI method to search candidate high-efficiency siRNAs on SARS-CoV-2's S gene. This study is one of the early studies applying RNAi therapy to the COVID-19 treatment. According to the analysis, the average value of predicted interference efficiency of the candidate siRNAs designed by the SMRI method is comparable to that of the mainstream siRNA design algorithms. Moreover, the SMRI method ensures that the designed siRNAs have more than three base mismatches with human genes, thus avoiding silencing normal human genes. This is not considered by other mainstream methods, thereby the five candidate high-efficiency siRNAs which are easy to take effect or synthesize and much safer for human body are obtained by our SMRI method, which provide a new safer, small dosage and long efficacy solution for the treatment of COVID-19.

Supplementary Information: The online version contains supplementary material available at 10.1007/s11390-021-0826-x.