Background: Antiviralactivity of natural compounds from Tinospora cordifolia (Amritaballi) were evaluated for their efficacy against SARS-CoV-2 targets involved in virus attachment and replication. Materials and Methods: The binding efficacy (binding affinity, Ki and IC50 values) of natural compounds from Tinospora cordifolia were tested using in silco tools against four key SARS-CoV-2 targets i.e., 1) surface glycoprotein (6VSB) and 2) Receptor binding domain (6M0J) both responsible for attachment of the virus to host cell, 3)RNA dependent RNA polymerase (6M71) and 4) main protease (6Y84) responsible for replication of the virus in the host cell. Results: Berberine, Isocolumbin, Magnoflorine and Tinocordiside howed high binding efficacy against all the four key SARS-CoV-2 targets. Tinocordiside and Isocolumbin showed IC50 value of < 1µM against both 6Y84 and 6VSB. Conclusion: At least fournatural compounds from Tinospora cordifolia showed high binding efficacy against SARS-CoV-2 targets involved in attachment and replication of the virus. Hence validating the merit of using Tinospora cordifolia in the clinical management of infection caused by SARS-CoV-2.