**3. Non nucleoside reverse transcriptase inhibitors (NNRTIs)**

The era of NNRTIs began before two decades, with the discovery of TIBO [4, 6] and HEPT [7] as specific inhibitors of reverse transcriptase. NNRTIs are highly specific and potent inhibitors of HIV-1 RT, and do not interfere with cellular or mitochondrial DNA synthesis [8]. However, the rapid emergence of resistant virus variants and the problem of resistance have limited their clinical use [9].

Nevirapine, Delavirdine and Efavirenz are the three Non nucleoside reverse transcriptase inhibitors which were approved as anti-HIV drugs in the year 1996, 1997 and 1998. Out of which Nevirapine is one the agent used to inhibit mother to child transmission of HIV [10–12].

Non Nucleoside Reverse Transcriptase Inhibitors (e.g. Nevirapine, Delavirdine, Efavirenz and Etravirine) are used as antiviral compounds which prevent the possibility transmission from mother to child. The interaction between NNRTI and NNRTI binding pocket mechanism from DNA polymerase active site has shown in **Figure 2.**

Basically in cytoplasm with the process of reverse transcription begins with entry of viral particle to the target cell of viral genome as a part of nucleoprotein conjugation whose structure is not well defined. This DNA is formed on the template of RNA but its terminal contains duplications which is known as long terminal repeats (LTRs)

#### **Figure 2.**

*Mechanism of NNRTI inhibition.*

#### **Figure 3.**

*Strand transfer reaction or jumps required to generate long terminal repeats (LTR's).*

*Substituted Azoles as Non-Nucleoside Reverse Transcriptase Inhibitors Activity DOI: http://dx.doi.org/10.5772/intechopen.110758*

**Figure 4.** *The structure of HIV-1 RT in the region near the polymerase active site.*

which is not present in viral RNA. (**Figure 3**) Strand transfer reactions or jumps are required to generate long terminal repeats (LTRs) which is perfect model for reverse transcription propose two specialized template switches [13, 14].

Reverse transcriptase enzyme is a type of replicative enzyme of HIV-1 and other type of retroviruses where retro viruses generates double stranded DNA by copying from single stranded genomic viral RNA and subsequently integrated with host cell DNA. Reverse transcriptase (RT) has two enzymatic activities: First one is polymerase which copy either DNA or RNA and second one is RNAase that degrade RNA strand of RNA-DNA intermediates formed during viral DNA synthesis. Human immunodeficiency syndrome virus (HIV-1) has two subunits p66 and p51. Polymerase chain of domain site p66 and p51 contain four subdomain namely fingers, palm, thumb and connection. Folding and connections of both subdomain p66 and p51 are similar in nature but their spatial arrangements are different. Domain p66 contains active site for both polymerase as well as RNAse while domain p51 plays primarily structural role for DNA and RNA.

Fingers and palm size of domain p66 are highly conserved region and together with two helices of thumb subdomain acts as a clamp that holds the position template primer (**Figure 4**). One of these region which is part of palm subdomain act as a primer group of DNA. The primer group is the candidate solely responsible for the exact placement of primer terminus at the active site of polymerase enzyme and involved in translocation of DNA template primer followed by 4–7 nucleotide incorporation. Exact positioning or binding of template primer is also very much important for cleavage of DNA/RNA template by the RNase activity of reverse transcription

enzyme. Now a days HIV-1 reverse transcriptase inhibitors currently available as anti HIV drugs in the management of AIDS by targeting enzymatic activity of DNA polymerase activity [15–17].
