A small interfering RNA (siRNA) database for SARS-CoV-2

Abstract

Coronavirus disease 2019 (COVID-19) rapidly transformed into a global pandemic, for which a demand for developing antivirals capable of targeting the SARS-CoV-2 RNA genome and blocking the activity of its genes has emerged. In this work, we propose a database of SARS-CoV-2 targets for siRNA approaches, aiming to speed the design process by providing a broad set of possible targets and siRNA sequences. Beyond target sequences, it also displays more than 170 features, including thermodynamic information, base context, target genes and alignment information of sequences against the human genome, and diverse SARS-CoV-2 strains, to assess whether siRNAs targets bind or not off-target sequences. This dataset is available as a set of four tables in a single spreadsheet file, each table corresponding to sequences of 18, 19, 20, and 21 nucleotides length, respectively, aiming to meet the diversity of technology and expertise among labs around the world concerning siRNAs design of varied sizes, more specifically between 18 and 21nt length. We hope that this database helps to speed the development of new target antivirals for SARS-CoV-2, contributing to more rapid and effective responses to the COVID-19 pandemic.

Potential Achilles heels of SARS-CoV-2 are best displayed by the base order-dependent component of RNA folding energy

“…Thus, we have here repeated and expanded on past clarifications [26, 30, 31] of the conceptual basis of a technology that has contributed to the understanding of a many biological problems other than viral infections [7]. Meanwhile, it is pleasing to note that, with minimal evidence on targeting, progress is being made with the second step [9, 10]. It is hoped that by targeting one or more of the conserved regions in the SARS-CoV-2 genome here identified, rapid cures will be achieved.…”

“…We here report similar highly conserved structural regions of the SARS-CoV-2 genome, one or more of which should be susceptible to targeting [9,10].…”

“…We here report similar highly conserved structural regions of the SARS-CoV-2 genome, one or more of which should be susceptible to targeting [9, 10]. We identify certain open reading frames (ORFs) that, because of their conservation, have so far attracted therapeutic interest mainly related to their functions at the protein level [11, 12], rather than at the level of the corresponding, yet highly structured, regions of the genome.…”

Ex vivo and in vivo suppression of SARS-CoV-2 with combinatorial AAV/RNAi expression vectors

“…Here we performed this analysis retrospectively, based on shRNAs that we had already selected at the beginning of the pandemic, when fewer SARS-CoV-2 strains were known. In the future, as demonstrated by others, [23][24][25][26] such an analysis can ideally be used to proactively identify optimal shRNA target regions with maximum conservation across SARS-CoV-2 variants, facilitating development of broadly active, next-generation AAV-SAVIOR permutations.…”

“…Concurrently, many groups have published databases of computationally predicted RNAi targets in SARS-CoV-2 and matching siRNA sequences. [23][24][25][26] These RNAi approaches are complemented by exciting studies from multiple labs illustrating the power and potential of CRISPR-Cas13 systems to inhibit SARS-CoV-2 expression and replication on the RNA level in vitro and in vivo. These include Cas13a, 27 Cas13b, 28 and Cas13d 29 and comprise use of nebulizers for delivery of Cas13a mRNA and associated guides to lungs of mice and hamsters.…”