Coronavirus hit the world badly and turned into a pandemic leading to the death of millions of people. Many vaccines and drugs launched in the market for the treatment of coronavirus but were not found very effective. This project was designed to search for new drugs against coronavirus from natural sources. Two new steroids were isolated from chloroform soluble extract of Nerium oleander. The structure of these compounds was isolated based on state-of-the-art spectroscopic techniques and were named cholest-5, 9 (11)-diene-2α, 3β-diol (1) and 3β-acetoxy-7, 9 (11)-diene cholestane (2). Both compounds were docked against SARS-CoV-2 using AutoDock vina. Two reactive sites were identified for SAR-COV-2 Mpro (PDB ID: 2GTB and 6LU7). Compound 1 inhibited the SAR-COV-2 Mpro (PDB ID: 2GTB) enzyme near favipiravir (standard drug). On the other hand, compounds 1 and 2 inhibited SAR-COV-2 Mpro (PDB ID: 6LU7) enzyme moderately as compared to favipiravir. Compounds 1 and 2 exhibited high binding affinities compared to remdesivir (standard drug) referring to the effectiveness of these compounds against SAR-COV-2.