The disclosure provides for ribozyme-mediated fusion constructs and systems and methods thereof, for use in a variety of applications, including for inducible gene expression systems, gene therapy, and combinatorial screening.

The present application relates to triterpene glycoside saponin-derived adjuvants, TLR4 agonists and antagonists, TLR9 agonists and antagonists, and combinations thereof, as well as pharmaceutical compositions comprising the foregoing and methods of making and of using the foregoing in the treatment of certain diseases.

In alternative embodiments, provided are pharmaceutical compositions comprising combinations of drugs, including products of manufacture and kits, and methods for using them, for treating, preventing, ameliorating, slowing the progress of, decreasing the severity of or preventing a coronavirus infection, or a COVID-19 or a 2019-nCoV (or so-called Wuhan coronavirus) infection, or an infection caused by a virus in the subfamily Orthocoronavirinae, or a virus in the family Coronaviridae, or a virus in the order Nidovirales. In alternative embodiments, combinations, or cocktails, of a drug or drugs as provided herein are administered either enterally, parenterally and/or by inhalation. In alternative embodiments, combinations, or cocktails, of drugs as provided herein are used to block intracellular metabolic pathways and prevent progression of the infection to clinical illness and death. In alternative embodiments, novel aerosol, spray or mist or powder formulations for inhalation are provided.

Techniques are provided for determining pan-HLA binding of viral proteins. A trained classifier model is operable to determine, independently per HLA, at least one of (a) an average binding prediction of overlapping peptides at each position of a viral protein, (b) a maximum value of a binding prediction of overlapping peptides at each position of the viral protein, (c) standard deviation of a binding prediction of overlapping peptides at each position of the viral protein, and (d) a combination of one or more of (a)-(c). A classification engine uses the classifier model to determine average binding predictions of overlapping peptides at each position of the viral protein independently for test HLA-I and HLA-II functional groupings, where a peptide is classified as a binder when an average binding prediction corresponding to the peptide satisfies a binding value threshold.