SiRNA Molecules as Potential RNAi Therapeutics to Silence RdRP Region and N-Gene of SARS-CoV-2: An In Silico Approach

Abstract

COVID-19 pandemic keeps pressing onward and effective treatment option against it is still far-off. Since the onslaught in 2020, 13 different variants of SARS-CoV-2 have been surfaced including 05 different variants of concern. Success in faster pandemic handling in the future largely depends on reinforcing therapeutics along with vaccines. As a part of RNAi therapeutics, here we developed a computational approach for predicting siRNAs, which are presumed to be intrinsically active against two crucial mRNAs of SARS-CoV-2, the RNA-dependent RNA polymerase (RdRp), and the nucleocapsid phosphoprotein gene (N gene). Sequence conservancy among the alpha, beta, gamma, and delta variants of SARS-CoV-2 was integrated in the analyses that warrants the potential of these siRNAs against multiple variants. We preliminary found 13 RdRP-targeting and 7 N gene-targeting siRNAs using the siDirect V.2.0. These siRNAs were subsequently filtered through different parameters at optimum condition including macromolecular docking studies. As a result, we selected 4 siRNAs against the RdRP and 3 siRNAs against the N-gene as RNAi candidates. Development of these potential siRNA therapeutics can significantly synergize COVID-19 mitigation by lessening the efforts, furthermore, can lay a rudimentary base for the in silico design of RNAi therapeutics for future emergencies.