Suppression of Sars Replication by Sars Helicase Inhibitors
AssigneeThe Curators of the University of Missouri
InventorsStefan G. Sarafianos, Adeyemi O. Adedeji, Kamlendra Singh
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Abstract
The present invention relates to compounds, compositions, and methods, for treating subjects suspected of needing treatment for a Nidovirales virus infection. In certain embodiments, the compounds comprise Nidovirales helicase inhibitors that do not significantly affect helicase ATPase enzymatic activity or nucleic acid binding activity of the helicase.
Claims33
A method for treating a subject suspected of needing treatment for a Nidovirales virus infection, comprising:
- administering an effective amount of a compound of formula II:
- a derivative, or a pharmaceutically acceptable salt thereof;
- wherein the effective amount is capable of inhibiting a Nidovirales virus helicase;
- wherein B represents Sulfur or Oxygen;
- wherein X, Y, and Z are independently selected from one another from the group consisting of H, —SH, and —O—R;
- wherein R is selected from the group consisting of H, alkyl, alkenyl, alkynyl, C3-C6 cyclo-alkyl, cyclo-alkyl-alkyl, aryl, hetero-aryl, aryl-alkyl, heteroaryl-alkyl, heterocyclyl, heterocycly-lalkyl, alkylsulfonyl, and arylsulfonyl.
A pharmaceutical composition comprising a compound of formula II:
- a derivative, or a pharmaceutically acceptable salt thereof;
- wherein B represents Sulfur or Oxygen;
- wherein X, Y, and Z are independently selected from one another from the group consisting of H, —SH, and —O—R;
- and wherein R is selected from the group consisting of H, alkyl, alkenyl, alkynyl, C3-C6 cyclo-alkyl, cyclo-alkyl-alkyl, aryl, hetero-aryl, aryl-alkyl, heteroaryl-alkyl, heterocyclyl, heterocycly-lalkyl, alkylsulfonyl, and arylsulfonyl.
A method of inhibiting replication of a Nidovirales virus comprising the step of contacting a sample containing the Nidovirales virus with a compound of formula I:
- a derivative or a salt thereof.
A method of inhibiting replication of a Nidovirales virus or treating a subject suspected of needing treatment for a Nidovirales virus infection comprising contacting a sample containing the Nidovirales virus or providing the subject suspected of needing treatment with a compound capable of inhibiting unwinding activity of a Nidovirales helicase, wherein the compound does not affect ATPase enzymatic activity or nucleic acid binding activity of the helicase.
A method of identifying an antiviral compound capable of inhibiting a Nidovirales virus replication, comprising:
- incubating a helicase of the Nidovirales virus with a substrate of the helicase in the presence of one or more candidate compounds;
- detecting helicase activity;
- relating helicase activity to one or more members of the plurality of candidate compounds;
- identifying one or more candidate compounds capable of inhibiting helicase unwinding activity;
- testing whether the one or more candidate compounds capable of inhibiting helicase activity affect ATPase enzymatic activity or nucleic acid binding activity of the helicase;
- identifying the antiviral compound against a Nidovirales virus, which is capable of inhibiting helicase unwinding activity without reducing ATPase enzymatic activity or nucleic acid binding activity.
A method of optimizing a lead compound, comprising:
- generating one or more chemical derivatives of the compound of formula I:
- testing the one or more derivatives for helicase unwinding-inhibitory activity, identifying one or more optimized lead compounds having an improved helicase-inhibitory-activity.
A method of optimizing a lead compound, comprising:
- generating one or more chemical derivatives of the compound of formula I:
- testing the one or more derivatives for Nidovirales virus replication suppression activity, and identifying one or more optimized lead compounds having an Nidovirales virus replication suppression activity.
Dependencies are inferred from the claim text.