SARS-CoV-2 (or COVID-19) has become a global risk and scientists are attempting to investigate antiviral vaccine.Berberisare important plants due to the presence of bioactive phytochemicals, especially berberine from the protoberberine group of benzylisoquinoline and recent studies have shown its potential in treating COVID-19.B. lyciumRoyle growing in subtropical regions of Asia had wide applications in Indian system of medicine. Rapid determination and novel optimisation method for berberine extraction has been developed by Soxhlet extraction utilising central composite design-response surface methodology (CCD-RSM). Berberine was detected by high-performance liquid chromatography (HPLC), and the highest yield (13.39%) was obtained by maintaining optimal extraction conditions i.e., extraction time (7.28 hrs), ethyl alcohol (52.21%) and solvent to sample ratio (21.78 v/w). Investigation of two geographic regions (Ramnagar and Srinagar) showed high berberine content in lower altitude. This novel optimisation technique has placed berberine as a potential candidate for developing pharmaceutical products for human health care.