Investigation of the pharmacophore space of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) NTPase/helicase by dihydroxychromone derivatives

Abstract

Aryl diketoacids have been identified as the first SARS-CoV NTPase/helicase inhibitors with a distinct pharmacophore featuring an arylmethyl group attached to a diketoacid. In order to search for the pharmacophore space around the diketoacid core, three classes of dihydroxychromone derivatives were prepared. Based on SAR study, an extended feature of the pharmacophore model of SARS-CoV NTPase/helicase was proposed which is constituted of a diketoacid core, a hydrophobic arylmethyl substituent, and a free catechol unit.

Development of chemical inhibitors of the SARS coronavirus: Viral helicase as a potential target

“…Analysis of amino acid sequence suggests that the SCV helicase has 2 separate domains: (1) a metal-binding domain (MBD) at the N-terminus and (2) a helicase domain (Hel) [22]. A detailed understanding of the biochemical mechanism mediated by SCV helicase became possible [25][26][27][28][29] after its purification [6,30].…”

“…However, in contrast to myricetin and scutellarein, they appeared to inhibit the duplex DNA-unwinding activity but not the ATPase activity of SCV helicase [26]. They have expanded the study by showing that dihydroxychromone derivatives, which are structural analogs of ADKs, can function as chemical inhibitors of the DNA-unwinding activity, but not of the ATPase activity, of SCV helicase [27]. Together, these SCV helicase inhibitors can serve as good candidates for development of SARS medication(s) in the future.…”

Discovering New Medicines Targeting Helicases: Challenges and Recent Progress

“…Similar compounds with only one arylmethyl or catechol group do not inhibit the SARS-CoV helicase. 162,163 …”

Carbon nanotubes supported tyrosinase in the synthesis of lipophilic hydroxytyrosol and dihydrocaffeoyl catechols with antiviral activity against DNA and RNA viruses

“…8 Moreover, they are active against viruses, as in the case of rhinovirus, 9 HIV-1 integrase, 10,11 HIV-1 reverse transcriptase, 12 and coronavirus. 13 The biological activity of catechols is associated to their antioxidant property, that is the capacity of transferring singleelectron and/or hydrogen-atom to reactive free radicals, 14,15,16 as well as, to binding pro-oxidant metal ions. 17 The antioxidant activity can be oriented toward specific cellular compartments by controlling the chemical and physical properties of the substituents on the aromatic ring.…”