Table 6. . Comparative overview of the properties of alpha-carboxynucleoside phosphonates and other HIV reverse transcriptase inhibitor classes.

Properties	α-CNP†	NRTI‡	NtRTI§	NNRTI¶
Nucleoside structure?	No	Yes	No	No
Nucleotide structure?	Yes	No	Yes	No
Metabolic activation required?	No	Yes (three steps)	Yes (two steps)	No
Enzyme inhibition versus dNTP substrate	Competitive	Competitive	Competitive	Noncompetitive
Binding to RT substrate-binding site?	Yes	Yes	Yes	No
Nature of the RT binding	Mutually exclusive with dNTP, but coordinating with Mg2+	Mutually exclusive with dNTP, but coordinating with Mg2+	Mutually exclusive with dNTP, but coordinating with Mg2+	Mutually nonexclusive with dNTP and Mg2+
Nucleobase-specific binding to template?	Yes	Yes	Yes	No
DNA chain termination?	No	Yes	Yes	No
Selective for HIV-1 RT?	No	No	No	Yes

^†α-Carboxynucleoside phosphonate.

^‡NRTI: Nucleoside RT inhibitor (e.g., zidovudine triphosphate).

^§NtRTI: Nucleotide RT inhibitor (e.g., tenofovir diphosphate).

^¶NNRTI: Non-nucleoside RT inhibitor (e.g., nevirapine or rilpivirine).

dNTP: 2’-Deoxyucleotide-5’-triphosphate; RT: Reverse transcriptase.