The reverse transcriptase (RT) of human immunodeficiency virus type-1 (HIV-1) is the essential enzyme converting the single-stranded viral RNA genome into double-stranded proviral DNA prior to its integration into the host genomic DNA. Nevirapine (Viramune®) was the first generation of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that has been approved by the FDA for the treatment of HIV-1 infection. Unfortunately, nevirapine and most NNRTIs showed a lack of affinity upon two important mutations, the K103N and Y181C mutations. Therefore, the aim of this work is to find novel inhibitors insensitive to the K103N and Y181C mutations, based on nevirapine and some NNRTIs. Virtual screening method is used to screen the compounds active against K103N and Y181C HIV-1 RT from a set of 500k commercially available drug-like compounds. GOLD program is the best possible docking/scoring strategy in this study. The compounds in the database were filtered by using pharmacophore searching. The 3D pharmacophore models were constructed based on the known important interactions between the amino acid in the binding pocket and NNRTIs. 45k compounds are found to match the phamacophore models and they are applied to molecular docking using the GOLD program. The hits from docking were selected and classified. Finally, the 32 selected compounds from the classification were tested for HIV-1 RT inhibition. Three compounds, BIO5935, BSP12957, and CHE63164, are found that their %inhibition are higher than 50.