SARS-CoV-2 has caused a global pandemic with significant humanity and economic loss since the beginning of 2020. Flaviviruses such as Zika and Dengue viruses are also significant human pathogens. Although SARS-CoV-2 vaccines are effective in preventing severe disease outcomes, they are less effective in controlling infection or re-infection, particularly due to rapid evolution of viral variants of SARS-CoV-2. Currently only limited options are available to treat SARS-CoV-2 and flavivirus infections for vulnerable populations. Potential of a future pandemic of other viruses is high. The present invention features compositions and methods for a universal high throughput screening (HTS) assay to identify inhibitors targeting the S-adenosyl-L-methionine (SAM)-binding site of viral methyltransferases (MTases) using SAM as a methyl donor.

Methods for diagnosing non-alcoholic steatohepatitis (NASH) and NASH with or without advanced liver fibrosis in a subject are provided, such methods including the detection of levels of a variety of biomarkers diagnostic of NASH versus simple steatosis and NASH with advanced liver fibrosis versus NASH without advanced liver fibrosis. The invention also provides methods treating NASH (e.g., NASH with or without advanced liver fibrosis) by administering a biomarker or an agent that modulates a biomarker of NASH or fibrosis. Compositions in the form of kits and panels of reagents for detecting the biomarkers of the invention are also provided.

Methods and compounds for labeling of biomolecules are disclosed. The method comprises combining a biomolecule-specific macromolecule and a reactive macromolecule ligand to effect labeling at or near known locations on the biomolecule.

Disclosed herein are methods, oligonucleotides, and kits for targeted cleavage and enrichment of nucleic acids for high-throughput analyses of user-defined genomic regions. Targeted sequence enrichment is an increasingly sought technology. Currently available methods exhibit biases and substantial proportions of off-target reads. Here, disclosed is FENGC, a versatile, multiplexed method, wherein oligonucleotide adapters and flap endonuclease direct 5 DNA flap formation and cutting that releases target sequences with nucleotide-level precision. The target-specific oligonucleotides are designed by a novel program called FENGC oligonucleotide designer (FOLD). Further disclosed are the oligonucleotides and kits required to perform FENGC.