The HIV-1 Protease is a homodimeric enzyme which is required in the HIV life cycle for cleavage of virus proteins prior to maturation. Although quite a number of HIV-1 Protease inhibitor drugs have been established, the major setback faced by most Anti Retroviral Therapies (ARTs) is the fact that the HIV is very susceptible to getting mutated, and some of these mutations are able to confer drug resistance to the HIV. Therefore it is imperative to identify new molecules which would be active against the mutant strains of HIV. In this study, we have employed a hybrid structure-based and ligand-based computational approach to identify novel lead compounds against the wild type and mutant strains of HIV-1 Protease, using Oleanolic acid as the reference ligand. Comparison of the docking results of our screened library with established drugs indicated that some plant steroidal alkaloids, including Condurangamine B and Rostratamine, showed better docking results than the established drugs, and therefore could be further explored as lead compounds.