Cindy Meyer
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Discovery, Optimization, and Evaluation of Non-Nucleoside SARS-CoV-2 NSP14 Inhibitors Open
We recently reported the discovery of TDI-015051, a first-in-class small-molecule inhibitor of the SARS-CoV-2 guanine-N7 methyltransferase nonstructural protein 14 (NSP14). NSP14 plays a critical role in viral RNA cap synthesis and its inh…
Discovery of Novel Isofunctional SARS-CoV-2 NSP14 RNA Cap Methyltransferase Inhibitors by Structure-Based Virtual Screening Open
In early 2020, SARS-CoV-2 spread into a worldwide pandemic, causing more than 7 million deaths. Direct-acting antivirals (DAAs) complementing vaccines and mitigating severe disease in at-risk populations remain important. Here, we used a s…
View article: Combination of antiviral drugs inhibits SARS-CoV-2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture
Combination of antiviral drugs inhibits SARS-CoV-2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture Open
SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations o…
Expanding the binding specificity for RNA recognition by a PUF domain Open
The ability to design a protein to bind specifically to a target RNA enables numerous applications, with the modular architecture of the PUF domain lending itself to new RNA-binding specificities. For each repeat of the Pumilio-1 PUF domai…
The E3 ubiquitin ligase RNF10 modifies 40S ribosomal subunits of ribosomes compromised in translation Open
Reversible monoubiquitination of small subunit ribosomal proteins RPS2/uS5 and RPS3/uS3 has been noted to occur on ribosomes involved in ZNF598-dependent mRNA surveillance. Subsequent deubiquitination of RPS2 and RPS3 by USP10 is critical …
View article: Combination of Antiviral Drugs to Inhibit SARS-CoV-2 Polymerase and Exonuclease as Potential COVID-19 Therapeutics
Combination of Antiviral Drugs to Inhibit SARS-CoV-2 Polymerase and Exonuclease as Potential COVID-19 Therapeutics Open
SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations o…
The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs Open
Cryptic polyadenylation within coding sequences (CDS) triggers ribosome-associated quality control (RQC), followed by degradation of the aberrant mRNA and polypeptide, ribosome disassembly and recycling. Although ribosomal subunit dissocia…