Your browser doesn't support javascript.
Characterization of Aurintricarboxylic Acid (ATA) Interactions with Plasma Transporter Protein and SARS-CoV-2 Viral Targets: Correlation of Functional Activity and Binding Energetics.
Minetti, Conceição A; Remeta, David P; Hashimoto, Keiji; Bonala, Radha; Chennamshetti, Rajesh; Yin, Xingyu; Garcia-Diaz, Miguel; Grollman, Arthur P; Johnson, Francis; Sidorenko, Viktoriya S.
  • Minetti CA; Department of Chemistry and Chemical Biology, Rutgers-The State University of New Jersey, Piscataway, NJ 08854, USA.
  • Remeta DP; Department of Chemistry and Chemical Biology, Rutgers-The State University of New Jersey, Piscataway, NJ 08854, USA.
  • Hashimoto K; Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
  • Bonala R; Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
  • Chennamshetti R; Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
  • Yin X; Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
  • Garcia-Diaz M; Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
  • Grollman AP; Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
  • Johnson F; Department of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
  • Sidorenko VS; Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
Life (Basel) ; 12(6)2022 Jun 10.
Article in English | MEDLINE | ID: covidwho-1911448
ABSTRACT
In an effort to identify functional-energetic correlations leading to the development of efficient anti-SARS-CoV-2 therapeutic agents, we have designed synthetic analogs of aurintricarboxylic acid (ATA), a heterogeneous polymeric mixture of structurally related linear homologs known to exhibit a host of biological properties, including antiviral activity. These derivatives are evaluated for their ability to interact with a plasma transporter protein (human serum albumin), eukaryotic (yeast) ribosomes, and a SARS-CoV-2 target, the RNA-dependent RNA polymerase (RdRp). The resultant data are critical for characterizing drug distribution, bioavailability, and effective inhibition of host and viral targets. Promising lead compounds are selected on the basis of their binding energetics which have been characterized and correlated with functional activities as assessed by inhibition of RNA replication and protein synthesis. Our results reveal that the activity of heterogeneous ATA is mimicked by linear compounds of defined molecular weight, with a dichlorohexamer salicylic-acid derivative exhibiting the highest potency. These findings are instrumental for optimizing the design of structurally defined ATA analogs that fulfill the requirements of an antiviral drug with respect to bioavailability, homogeneity, and potency, thereby expanding the arsenal of therapeutic regimens that are currently available to address the urgent need for effective SARS-CoV-2 treatment strategies.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Language: English Year: 2022 Document Type: Article Affiliation country: Life12060872

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Language: English Year: 2022 Document Type: Article Affiliation country: Life12060872