New roles explored for nucleoside reverse transcriptase inhibitors

Nucleoside reverse transcriptase inhibitors (NRTIs) which blocks retroviral replication in people infected with HIV, could be used to halt macular degeneration (pictured), research finds

Nucleoside reverse transcriptase inhibitors (NRTIs) block retroviral replication in people infected with HIV. New research reveals that these drugs have another, unrelated effect: suppressing a large protein complex known as NLRP3 (NOD-like receptor family, pyrin domain containing 3) involved in innate immunity, and implicated in a range of diseases.

A team of researchers at University of Kentucky in Lexington evaluated multiple NRTIs in mouse models of NLRP3-inflammasome-driven diseases, including macular degeneration, geographic atrophy, choroidal neovascularisation, graft-versus-host disease and sterile liver inflammation.

They found that NRTIs inhibit P2X7-mediated NLRP3 inflammasone activation independent of reverse transcriptase inhibition. 

The findings suggest that NRTIs are ripe for drug repurposing, suggest the authors in Science
, adding that NRTIs have many advantages, including being inexpensive and safe. The team will now evaluate whether NRTIs can halt the progression of acute macular degeneration in patients.


 [1] Fowler BJ, Gelfand BD, Kim Y et al. Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity. Science 2014;346:1000–1003. DOI:10.1126/science.1261754.

Last updated
The Pharmaceutical Journal, PJ, 6/13 December 2014, Vol 293, No 7839/40;293(7839/40):DOI:10.1211/PJ.2014.20067276

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