Substituted nucleosides, nucleotides and analogs thereof

A method for ameliorating or treating a Picornaviridae viral infection comprising contacting a cell infected with the Picornaviridae virus with an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) has the structure:

• wherein:
• B1A is
• wherein RG2 is an unsubstituted C1-6 alkyl;
• R3A is selected from the group consisting of OH, OC(═O)R″A and an unsubstituted O-linked α-amino acid;
• R4A is selected from the group consisting of OH and halo;
• Ra1 and Ra2 are independently hydrogen or deuterium;
• RA is hydrogen or deuterium;
• R1A is selected from the group consisting of hydrogen,
• R2A is halo;
• R5A is selected from the group consisting of an unsubstituted C1-6 alkyl and an unsubstituted C2-6 alkenyl;
• R6A and R7A are independently selected from the group consisting of absent, hydrogen and
• or
• R6A is
• and R7A is absent or hydrogen;
• or
• R8A is absent, hydrogen, an optionally substituted phenyl or an optionally substituted naphthyl;
• R9A is an optionally substituted N-linked amino acid selected from the group consisting of N-linked alanine, N-linked asparagine, N-linked aspartate, N-linked cysteine, N-linked glutamate, N-linked glutamine, N-linked glycine, N-linked proline, N-linked serine, N-linked tyrosine, N-linked arginine, N-linked histidine, N-linked isoleucine, N-linked leucine, N-linked lysine, N-linked methionine, N-linked phenylalanine, N-linked threonine, N-linked tryptophan and N-linked valine, or an optionally substituted N-linked α-amino acid ester derivative, wherein the optionally substituted N-linked α-amino acid ester derivative is an unsubstituted C1-6 alkyl ester, an optionally substituted C3-6 cycloalkyl ester, an optionally substituted C6 aryl ester, an optionally substituted C10 aryl ester or an optionally substituted benzyl ester of an N-linked α-amino acid selected from the group consisting of N-linked alanine, N-linked asparagine, N-linked aspartate, N-linked cysteine, N-linked glutamate, N-linked glutamine, N-linked glycine, N-linked proline, N-linked serine, N-linked tyrosine, N-linked arginine, N-linked histidine, N-linked isoleucine, N-linked leucine, N-linked lysine, N-linked methionine, N-linked phenylalanine, N-linked threonine, N-linked tryptophan and N-linked valine;
• R10A and R11A are independently an optionally substituted N-linked amino acid selected from the group consisting of N-linked alanine, N-linked asparagine, N-linked aspartate, N-linked cysteine, N-linked glutamate, N-linked glutamine, N-linked glycine, N-linked proline, N-linked serine, N-linked tyrosine, N-linked arginine, N-linked histidine, N-linked isoleucine, N-linked leucine, N-linked lysine, N-linked methionine, N-linked phenylalanine, N-linked threonine, N-linked tryptophan and N-linked valine, or an optionally substituted N-linked α-amino acid ester derivative, wherein the optionally substituted N-linked α-amino acid ester derivative is an unsubstituted C1-6 alkyl ester, an optionally substituted C3-6 cycloalkyl ester, an optionally substituted C6 aryl ester, an optionally substituted Cm aryl ester or an optionally substituted benzyl ester of an N-linked α-amino acid selected from the group consisting of N-linked alanine, N-linked asparagine, N-linked aspartate, N-linked cysteine, N-linked glutamate, N-linked glutamine, N-linked glycine, N-linked proline, N-linked serine, N-linked tyrosine, N-linked arginine, N-linked histidine, N-linked isoleucine, N-linked leucine, N-linked lysine, N-linked methionine, N-linked phenylalanine, N-linked threonine, N-linked tryptophan and N-linked valine;
• R12A and R13A are independently absent or hydrogen;
• R14A is O−, OH or methyl;
• R22A and R23A are each hydrogen;
• R24A is selected from the group consisting of hydrogen, an unsubstituted C1-24 alkyl, and an unsubstituted —O—C1-24 alkyl;
• R″A is an unsubstituted C1-24 alkyl;
• m is 0 or 1;
• s is 0, 1, 2 or 3;
• and
• Z1A, Z2A, Z3A and Z4A are each O.