Macrocyclic and peptidomimetic compounds as broad-spectrum antivirals against 3C or 3C-like proteases of picornaviruses, caliciviruses and coronaviruses

An antiviral compound comprising:

• or the pharmaceutically-acceptable salts thereof, where:
• each X is selected from the group consisting of aldehydes;
• adducts of aldehydes or keytones;
• ketoamides;
• α-hydroxyphosphonates;
• and ketones;
• each R0 is —CH—or —N—;
• each R1 is a natural or non-naturally occurring amino acid side chain selected from the group consisting of branched or unbranched alkyl, cycloalkyl, aryl, arylalkyl, or a combination thereof;
• each R2 is selected from the group consisting of —C(O)OR8, where R8 is alkyl, cycloalkyl, or substituted or unsubstituted:
• aryl, arylalkyl, aryloxy, heteroaryloxy, arylalkoxy, heteroarylalkoxy, or aromatic heterocyclic ring;
• —C(O)NHR9, where R9 is alkyl, cycloalkyl, or substituted or unsubstituted:
• aryl, arylalkyl, aryloxy, heteroaryloxy, arylalkoxy, heteroarylalkoxy, or aromatic heterocyclic ring;
• and —SO2R10, where R10 is alkyl, cycloalkyl, or substituted or unsubstituted:
• aryl, arylalkyl, aryloxy, heteroaryloxy, arylalkoxy, heteroarylalkoxy, or aromatic heterocyclic ring;
• each R3 is selected from the group consisting of
• and —(CH2)2C(O)NR14R15, where R14 is alkyl, cycloalkyl, or arylalkyl, and R15 is H or alkyl, or R14 and R15 are tethered together to form a cyclic amine;
• each W is selected from the group consisting of —(CH2)x—, where x is 4 to 10;
• —CH2Q (CH2)z—, where Q is S or O, and z is 4 to 8;
• —(CH2)mC(O)NR11(CH2)p—, where R11 is H or methyl, m is 1 to 2, and p is 3 to 6;
• —CH2Im(CH2)r—, where Im is imidazole and r is 3 to 6;
• —(CH2)sTr(CH2)s—, where Tr is a 1,4—or 1,5-substituted triazole and each s is 1 to 4;
• and —(CH2)tR12(CH2)t-, where R12 is a phenyl or heterocyclic ring, and each t is 1 to 4;
• and
• each Y is —CH2— or NR13, where R13 is H, alkyl, cycloalkyl, or arylalkyl.