A novel coronavirus designated as SARS-CoV-2 originated in Wuhan city in Hubei Province of China at the end of 2019.This been recently declared as Global Pandemic by WHO and termed as disease COVID-19. This believed to be Zoonotic in origin mainly from an Intermediate Horse shoe bat and suspected intermediate host of unknown origin. As of 11 May 2020, World had 4.1 Million confirmed cases in total, 1.4 Million recovered and deaths around 282000.There is a global emergency to identify potential drugs to treat the SARS-CoV-2. Currently, there is no specific treatment against the new virus. There is urgency to identifying potential antiviral agents or Vaccines to combat the disease. Many Repurposed been proposed, but most of them have toxicity and not specific to viral host cell inhibitors. Natural compounds proved many times as antiviral agents and have potential to act as host cell entry inhibitors. Dammarane and Ergostane terpenoid derivatives are such category of natural compounds selected to study as entry inhibitors of SARS-CoV-2. Dammarane compounds like Protopanaxidiols, Panaxatriol, Betulin, Stigmasterols like Betasitosterol and Ergostane compounds like Withanolide in comparison with AI predicted Thiocolchicoside and Prednisone were selected as ligands and docked against SARS-CoV-2 spike glycoprotein PDB ID 6VXX. Protopanaxidiols, Panaxatriol, Betulin, Arcapitin, Betasitosterol, prednisone, Thiocolchicoside, Withanolide compounds had shown strong binding with spike glycoprotein with ΔG -6.98, -6.5, -5.8,-6.02 -5.9, -5.95,-6.0, -6.75 kcal and Estimated Inhibition Constant, Ki values 100 uM, 70 uM, 43 uM, 18 uM, 25 uM, 42 uM, 54 uM and 23 uM. Betasitosterol, Panaxatriol and Betulin had shown cation pi interaction indicating strong binding efficacy. Amino acid side chain interaction of ligand with TYR, SER, ASN, THR, GLN, ARG, LEU of spike protein shown the selected molecules have good inhibitory effect against SARS-CoV-2. Thus we propose to study the cell entry inhibitory effect of Dammarane and Ergostane derivatives along with lactone skeleton in their structure via In-vitro In-vivo
methods and to conduct proper clinical trials among COVID-19 patients.