J. J. Arnold

Discovery of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach

This paper identifies and characterizes RA-0002034, a covalent inhibitor of CHIKV nsP2 protease, showing potent inhibition and selectivity against alphaviruses.

Enteroviral 2C protein is an RNA-stimulated ATPase and uses a two-step mechanism for binding to RNA and ATP

This study elucidates the biochemical mechanism of enteroviral 2C protein's ATPase activity, showing RNA stimulates ATP hydrolysis via a two-step binding mechanism.

Interfering with nucleotide excision by the coronavirus 3'-to-5' exoribonuclease

This study investigates how SARS-CoV-2's ExoN enzyme processes RNA and identifies modifications that block its activity, offering potential for new antiviral strategies.

IRES-independent, eIF2A/eIF2D-dependent translation of the enterovirus genome

This study shows that enterovirus genome recombination depends on eIF2A/eIF2D-dependent translation, not IRES-mediated translation, and explains non-replicative recombination and RNA persistence.

The nucleotide addition cycle of the SARS-CoV-2 polymerase

This study describes the mechanochemical behavior of the SARS-CoV-2 polymerase using magnetic tweezers, revealing three catalytic conformations and a thermal ratchet mechanism for nucleotide incorporation.

Inhibition of SARS-CoV-2 polymerase by nucleotide analogs: a single moleculeperspective

This study investigates how nucleotide analogs like Remdesivir affect SARS-CoV-2 polymerase activity using single-molecule techniques, revealing backtracking rather than termination and evasion of ddhCTP.

Induced copy-back RNA synthesis as a novel therapeutic mechanism against RNA viruses

This study shows that a ribonucleotide analogue induces copy-back RNA synthesis, a new mechanism to combat RNA viruses by promoting defective viral genomes.

Temperature controlled high-throughput magnetic tweezers show striking difference in activation energies of replicating viral RNA-dependent RNA polymerases.

This study uses temperature-controlled magnetic tweezers to compare replication kinetics of RdRps from three RNA viruses, finding temperature-dependent activation differences.

A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus

This study shows that RNA viruses evolve high mutation rates as a byproduct of selection for faster replication, not because of adaptive advantages.