May 3, 2022The Journal of Physical Chemistry Letters
2′- and 3′-Ribose Modifications of Nucleotide Analogues Establish the Structural Basis to Inhibit the Viral Replication of SARS-CoV-2
Key result
3'-hydrogen substitution in simulations exerts immediate SARS-CoV-2 RdRp chain termination without compromising active site stability.
Why the study?
The structural basis of inhibition of SARS-CoV-2 RNA-dependent RNA polymerase by nucleotide analogues with 3'-ribose modification and other 2'-ribose modifications is not fully understood.
Population
SARS-CoV-2 RNA-dependent RNA polymerase model
Comparison
Adenosine analogues with 2'- and/or 3'-ribose modifications
Design
Comprehensive structural analysis using molecular dynamics simulations
Authors
Discussion
Loading...
Member takes
Implication
Supports 3'-hydrogen substitution for stable chain termination; leaves open clinical translation from animal RdRp models.
Structured PICO
P
Population
SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) model (molecular dynamics simulations)
I
Intervention
Adenosine analogues with 2'- and/or 3'-modifications
O
Outcome
Structural stability and chain termination potentialsurrogate
3'-hydrogen substitution of nucleotide analogues provides a promising modification scheme for developing obligate chain terminators against SARS-CoV-2 RdRp.
Cite This Study
Li et al. (2022) studied SARS-CoV-2. Adenosine analogues with 2'- and/or 3'-modifications was evaluated on Structural stability and chain termination potential. Molecular dynamics simulations suggest that 3'-hydrogen substitution inherently exerts immediate chain termination of SARS-CoV-2 RdRp without compromising structural stability in the active site.