Substituted nucleosides, nucleotides and analogs thereof

A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure:

• wherein:
• B1 is selected from the group consisting of an optionally substituted
• and an optionally substituted
• -------- is absent or a single bond;
• when ------ is a single bond, then RP is
• and R4 is O;
• when ------ is absent, then RP is hydrogen or
• and R4 is —OH or F;
• R1 is selected from the group consisting of an —0-optionally substituted aryl,
• O−, and —OH;
• R2 is selected from the group consisting of O−, —OH, an optionally substituted N-linked amino acid, an optionally substituted N-linked amino acid ester derivative and
• provided that when R2 is O− or —OH, R1 is selected from the group consisting of
• O− and —OH;
• R3, each R6 and R7 are independently hydrogen or deuterium;
• R5 is F;
• R8, R9 and R10 are independently absent or hydrogen;
• B3A and B4A are independently hydrogen or deuterium;
• B5A is —O-optionally substituted C1-6 alkyl or —NH2;
• Rp1 is selected from the group consisting of O−, OH, an —O-optionally substituted C1-6 alkyl, an —O-optionally substituted aryl,
• an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative;
• Rp2, Rp3, Rp5 and Rp6 are independently selected from the group consisting of hydrogen, an optionally substituted C1-24 alkyl and an optionally substituted aryl;
• Rp4 and Rp7 are independently selected from the group consisting of hydrogen, an optionally substituted C1-24 alkyl, an optionally substituted aryl, an optionally substituted —O—C1-24 alkyl, an optionally substituted —O-aryl, an optionally substituted —O-heteroaryl and an optionally substituted —O-monocyclic heterocyclyl;
• Rp8 and Rp9 are independently selected from the group consisting of hydrogen, an optionally substituted C1-24 alkyl and an optionally substituted aryl;
• n is 0 or 1;
• r is 1 or 2;
• u is 3, 4, or 5;
• and
• Zp1 is O or S.