Using Folding Ensemble and Stem Probability Maximization Methods to Predict RNA H-Type Pseudoknots

We present in this paper an ab initio method, named KnotFold, for RNA H-type pseudoknot prediction. Our method employs an ensemble of RNA folding tools and a filtering heuristic to generate a set of pseudoknot-free stems, and then predicts pseudoknots by utilizing a search technique with a pseudo-probability scoring scheme. Experimental results show that KnotFold achieves higher sensitivity than existing methods. The KnotFold package with documentation is freely available at http：//bioinformatics.njit.edu/KnotFold.

Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed–1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity.Here,we show that carrimycin,a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials,decreases the efficiency of programmed–1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion.Carrimycin binds directly to the coronaviral frameshift-stimulatory element(FSE)RNA pseudoknot,interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes.Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses.Because the FSE mechanism is essential in all coronaviruses,carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA.This finding may open a new direction in antiviral drug discovery for coronavirus variants.

Molecular Dynamics Simulation of RNA Pseudoknot Unfolding Pathway

Many biological functions of RNA molecules are re- lated to their pseudoknot structures. It is significant for predicting the structure and function of RNA that learning about the stability and the process of RNA pseudoknot folding and unfolding. The structural features of mouse mammary tumor virus （MMTV） RNA pseudoknot in different ion concentration, the unfolding process of the RNA pseudoknot, and the two hairpin helices that constitute the RNA pseudoknot were studied with all atom molecule dynam- ics simulation method in this paper. We found that the higher cation concentration can cause structure of the RNA molecules more stable, and ions played an indispensable role in keeping the structure of RNA molecules stable; the unfolding process of hair- pin structure was corresponding to the antiprocess of its folding process. The main pathway of pseudoknot unfolding was that the inner base pair opened first, and then, the two helices, which formed the RNA pseudoknot opened decussately, while the folding pathway of the RNA pseudoknot was a helix folding after forma- tion of the other helix. Therefore, the unfolding process of RNA pseudoknot is different from the antiprocess of its folding process, and the unfolding process of each helix in the RNA pseudoknot is similar to the hairpin structure＇s unfolding process, which means that both are the unzipping process.