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7158740 
Journal Article 
The Journey of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from Lab to Clinic 
Namasivayam, V; Vanangamudi, M; Kramer, VG; Kurup, S; Zhan, P; Liu, X; Kongsted, J; Byrareddy, SN; , 
2019 
Yes 
Journal of Medicinal Chemistry
ISSN: 0022-2623
EISSN: 1520-4804 
AMER CHEMICAL SOC 
WASHINGTON 
4851-4883 
30516990 
WOS:000469304500003 
Human immunodeficiency virus (HIV) infection is now pandemic. Targeting HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a definitive place due to their unique antiviral potency, high specificity, and low toxicity in antiretroviral combination therapies used to treat HIV. Until now, >50 structurally diverse classes of compounds have been reported as NNRTIs. Among them, six NNRTIs were approved for HIV-1 treatment, namely, nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), etravirine (ETR), rilpivirine (RPV), and doravirine (DOR). In this perspective, we focus on the six NNRTIs and lessons learned from their journey through development to clinical studies. It demonstrates the obligatory need of understanding the physicochemical and biological principles (lead optimization), resistance mutations, synthesis, and clinical requirements for drugs.