Nonnucleoside

Nonnucleoside refers to any chemical species that is not a nucleoside, i.e., not a purine or pyrimidine base linked to a sugar (ribose or deoxyribose) without phosphate. In scientific literature the modifier nonnucleoside is often used for a class of antiretroviral drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). These agents are active against HIV-1 and do not require intracellular phosphorylation to an active form, unlike nucleoside/nucleotide reverse transcriptase inhibitors.

NNRTIs bind to a hydrophobic allosteric pocket in reverse transcriptase, causing conformational changes that reduce polymerase activity and replication. They are generally used in combination with NRTIs as part of highly active antiretroviral therapy. Examples include nevirapine, efavirenz, etravirine, rilpivirine, and doravirine; older agents include delavirdine. Resistance can emerge through mutations in the RT enzyme that reduce binding affinity. Cross-resistance patterns vary among compounds.

Pharmacokinetics and safety: NNRTIs are primarily metabolized by liver enzymes such as CYP3A4; they can interact with other drugs and food, and certain agents have notable central nervous system or hepatotoxic adverse effects. They do not resemble nucleoside structures, which differentiates them from NRTIs that act as nucleoside analogs and require phosphorylation to become active.

In non-medical contexts, nonnucleoside simply means not a nucleoside, used to describe molecules lacking a sugar-base structure. The term is highly contextual, with HIV therapy being a common reference.