Idenix Pharmaceuticals, Inc.

Universitá Degli Studi Di Cagliari

Centre National De La Recherche Scientifique

L'université Montpellier Ii

University of Cagliari

Paolo LaColla

Jean-Pierre Sommadossi

Gilles J Gosselin

Vadim Bichko

David N Standring

Lin Qu

Adel M Moussa

Richard Storer

Marino Artico

Romano Silvestri

A method and composition for treating a host infected with flavivirus or pestivirus comprising administering an effective flavivirus or pestivirus treatment amount of a described 1', 2&#x2032; or 3&#x2032;-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Methods and compositions for treating flaviviruses and pestiviruses

The present invention discloses a method for the treatment of Flaviviridae infection that includes the administration of a 2'-branched nucleoside, or a pharmaceutically acceptable prodrug and/or salt thereof, to a human in need of therapy in combination or alternation with a drug that directly or indirectly induces a mutation in the viral genome at a location other than a mutation of a nucleotide that results in a change from serine to a different amino acid in the highly conserved consensus sequence, XRXGXXXT (SEQ ID NO: 63), of domain B of the RNA polymerase region, or is associated with such a mutation. The invention also includes a method to detect a mutant strain of Flaviviridae and a method for its treatment.

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The present invention discloses a method for the treatment of Flaviviridae infection that includes the administration of a 2'-branched nucleoside, or a pharmaceutically acceptable prodrug and/or salt thereof, to a human in need of therapy in combination or alternation with a drug that directly or indirectly induces a mutation in the viral genome at a location other than a mutation of a nucleotide that results in a change from seine to a different amino acid in the highly conserved consensus sequence, XRXSGXXXT (Sequence ID No. 63), of domain B of the RNA polymerase region, or is associated with such a mutation. The invention also includes a method to detect a mutant strain of Flaviviridae and a method for its treatment.

2'-branched nucleosides and Flaviviridae mutation

The 3'-L-valine ester of &#x3b2;-D-2&#x2032;-C-methyl-ribofuranosyl cytidine provides superior results against flaviviruses and pestiviruses, including hepatitis C virus. Based on this discovery, compounds, compositions, methods and uses are provided for the treatment of flaviviridae, including HCV, that include the administration of an effective amount of val-mCyd or its salt, ester, prodrug or derivative, optionally in a pharmaceutically acceptable carrier. In an alternative embodiment, val-mCyd is used to treat any virus that replicates through an RNA-dependent RNA polymerase.

2'-C-methyl-3&#x2032;-O-L-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections

This invention is in the area of phenylindoles that are useful for the treatment of HIV infection, and, in particular, phenylindoles that exhibit significant activity against resistant strains of HIV. The phenylindoles have at least two substituents other than hydrogen on the benzo ring of the indole function, preferably at the 4' and 5&#x2032;, 5&#x2032; and 6&#x2032; or the 5&#x2032; and 7&#x2032; positions, optionally in combination with disubstitution at positions 3&#x2033; and 5&#x2033; on the phenyl ring of the compound, and carboxamide containing moieties at position-2 on the indole group of the compound. Methyl is a preferred group for substitution on the phenyl ring. Preferred substituents for the benzo ring of the indole function include but are not limited to chlorine, fluorine, bromine, iodine, CF, methoxy, CN, and NO.

Substituted phenylindoles for the treatment of HIV

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Capoterra, Italy

Paolo LaColla