Jamie J. Arnold

Recovery of proofreading-impaired SARS-CoV-2 reveals a mutator phenotype and an ExoN activity threshold for viability

This paper shows SARS-CoV-2 can tolerate reduced proofreading activity but requires a minimal ExoN activity threshold for viability, leading to a mutator phenotype and reduced replication efficiency.

Linking the kinetic mechanism to structural dynamics required for nucleotide hydrolysis by an alphavirus nsP2 RNA helicase

This study characterizes the kinetic mechanism and structural dynamics of Chikungunya virus nsP2 RNA helicase during nucleotide hydrolysis using biochemical and computational methods.

Accurate single-bead force calibration in high-throughput magnetic tweezers reveals the mechanism of directional transcription termination by MTERF1

This paper develops an in-situ force calibration method for magnetic tweezers and uses it to reveal how MTERF1 causes directional transcription termination through DNA unwinding and a kinetic barrier.

RNA virus polymerase-helicase coupling enables rapid elongation throughduplex RNA

This study shows that the coronavirus helicase enhances RNA synthesis through duplex RNA by tenfold by forming a directional complex with the polymerase, revealing an active coupling mechanism that modulates replication dynamics.

Unwinding of an RNA duplex by the Orthoflavivirus NS3 helicase requires translocation beyond the displaced strand and is stimulated by the NS5 RdRp

This study investigates the RNA unwinding mechanism of orthoflavivirus NS3 helicases, finding that they require translocation beyond the displaced strand and are stimulated by NS5 RdRp.

A fold switch regulates conformation of an alphavirus virus RNA-dependent RNA polymerase

This study identifies a fold switch in ONNV nsP4 that regulates its conformation, RNA binding, and polymerase activity through proteolytic cleavage and fold switching.

Novel Computational Pipeline to Identify Target Sites for Broad Spectrum Antiviral Drugs

This paper develops a computational pipeline to identify conserved antiviral target sites in alphaviruses using AI-driven methods, validating potential drug targets through mutagenesis.

Minimal polymerase-containing precursor required for Chikungunya virus RNA synthesis

This study identifies a minimal functional precursor of CHIKV nsP4 required for RNA synthesis and shows cleavage by nsP2 protease is essential for replication.

Template switching by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir

This study shows that coronavirus polymerase template switching is driven by nsp13-helicase and is enhanced by remdesivir and molnupiravir, leading to defective RNA production.

The 2'-endo conformation of arabinose-CTP and arabinose-UTP inhibit viral polymerases by inducing long pauses.

This study shows that arabinose nucleotides inhibit SARS-CoV-2 and poliovirus polymerases by causing long pauses due to the 2'-endo conformation of the incorporated nucleotides.

An Enantioselective Chemical Probe for Chikungunya nsP2 Helicase with Antialphaviral Activity

The paper describes the enantioselective resolution of a chemical probe targeting CHIKV nsP2 helicase, showing potent antiviral activity for one enantiomer and low activity for the other.

Identification of a Broadly Acting Inhibitor of the Alphavirus Non-Structural Protein 2 Helicase

This study identifies a first-in-class inhibitor of alphavirus nsP2 helicase activity, showing broad antiviral activity and in vivo efficacy against chikungunya virus.

A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent

The paper shows that the SARS-CoV-2 polymerase core RTC undergoes a conformational change after RNA binding to become elongation-competent, which is essential for viral RNA synthesis.

Mechanism of forced-copy-choice RNA recombination by enteroviral RNA-dependent RNA polymerases

This paper investigates how enteroviral RNA-dependent RNA polymerases perform forced-copy-choice RNA recombination, showing the role of a plus-one intermediate and preference for CMP over other nucleotides.

Identification of Direct-acting nsP2 Helicase Inhibitors with Anti-alphaviral Activity

This paper identifies and optimizes oxaspiropiperidine inhibitors targeting nsP2hel, showing nanomolar antiviral activity against multiple alphaviruses.

Single-cell virology: On-chip, quantitative characterization of the dynamics of virus spread from one single cell to another

This study uses a microfluidic device to characterize lytic and non-lytic virus spread between single cells, finding non-lytic spread is faster and more efficient.

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.

Multiple Poliovirus-Induced Organelles Suggested By Comparison Of Spatiotemporal Dynamics Of Membranous Structures And Phosphoinositides

The paper investigates PV-induced organelles by analyzing spatiotemporal dynamics of PI4P and membrane structures, suggesting distinct organelles for genome replication and virus assembly.

Genetic recombination of poliovirus facilitates subversion of host barriers to infection

This study shows that poliovirus recombination is important for pathogenesis in animals but detrimental to replication in tissue culture, suggesting recombination aids viral spread within hosts.