The rapid spread of COVID-19 is motivating development of antivirals targeting conserved SARS-CoV-2 molecular machinery. The SARS-CoV-2 genome includes conserved RNA elements that offer potential small-molecule drug targets, but most of their 3D structures have not been experimentally characterized. Here, we provide a compilation of chemical mapping data from our and other labs, secondary structure models, and 3D model ensembles based on Rosetta\'s FARFAR2 algorithm for SARS-CoV-2 RNA regions including the individual stems SL1-8 in the extended 5\' UTR; the reverse complement of the 5\' UTR SL1-4; the frameshift stimulating element (FSE); and the extended pseudoknot, hypervariable region, and s2m of the 3\' UTR. For eleven of these elements (the stems in SL1-8, reverse complement of SL1-4, FSE, s2m and 3\' UTR pseudoknot), modeling convergence supports the accuracy of predicted low energy states; subsequent cryo-EM characterization of the FSE confirms modeling accuracy. To aid efforts to discover small molecule RNA binders guided by computational models, we provide a second set of similarly prepared models for RNA riboswitches that bind small molecules. Both datasets (\'FARFAR2-SARS-CoV-2\', https://github.com/DasLab/FARFAR2-SARS-CoV-2; and \'FARFAR2-Apo-Riboswitch\', at https://github.com/DasLab/FARFAR2-Apo-Riboswitch\') include up to 400 models for each RNA element, which may facilitate drug discovery approaches targeting dynamic ensembles of RNA molecules.

This document summarizes the current consensus opinion of the Exaggerated Pharmacology (EP) Subcommittee of the Oligonucleotide Safety Working Group on the appropriate strategies to assess potential adverse effects caused by an \"exaggerated\" degree of the intended pharmacologic activity of an oligonucleotide (ON). The Subcommittee focused its discussions primarily on the ON subclasses that impact expression of \"host\" (i.e., human gene products--antisense, small interfering RNAs, and related ONs that target messenger RNA), with later and more limited discussions on aptamer, immunostimulatory, and microRNA subclasses. It is expected that many of these principles will be relevant to other subclasses but will need to be carefully considered as those development programs advance towards clinical trials. The recommendations may also serve as a frame of reference when designing Good Laboratory Practice safety studies with ONs, with regard to the study design elements that address assessment of EP. It is also hoped that these recommendations will establish a foundation for discussion with regulatory agencies on this subject.