Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.7.48 (
transcriptase
)
9,479
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The COVID-19 pandemic threatens to overwhelm healthcare systems around the world. The only current FDA-approved treatment, which directly targets the virus, is the ProTide prodrug remdesivir. In its activated form, remdesivir prevents viral replication by inhibiting the essential
RNA-dependent RNA polymerase
. Like other ProTide prodrugs, remdesivir contains a chiral phosphorus center. The initial selection of the (
S
P
)-diastereomer for remdesivir was reportedly due to the difficulty in producing the pure (
R
P
)-diastereomer of the required precursor. However, the two currently known enzymes responsible for the initial activation step of remdesivir are each stereoselective and show differential tissue distribution. Given the ability of the COVID-19 virus to infect a wide array of tissue types, inclusion of the (
R
P
)-diastereomer may be of clinical significance. To help overcome the challenge of obtaining the pure (
R
P
)-diastereomer of remdesivir, we have developed a novel chemoenzymatic strategy that utilizes a stereoselective variant of the
phosphotriesterase
from
Pseudomonas diminuta
to enable the facile isolation of the pure (
R
P
)-diastereomer of the chiral precursor for the chemical synthesis of the (
R
P
)-diastereomer of remdesivir.
...
PMID:A Chemoenzymatic Synthesis of the (
R
P
)-Isomer of the Antiviral Prodrug Remdesivir. 3278 1
