This study evaluates the potential of natural alkaloids as therapeutic agents against SARS-CoV-2 by targeting the main protease and spike glycoprotein. The research involved docking 102 known alkaloids against these two key viral proteins, identifying six dual inhibitory compounds: liensinine, neferine, isoliensinine, fangchinoline, emetine, and acrimarine F. These compounds showed strong binding affinities, with neferine demonstrating the highest scores for both proteins. The study also assessed the stability of these compounds through molecular dynamics simulations and evaluated their ADMET properties, bioactivity scores, and drug-likeness. Neferine and emetine exhibited low toxicity and high LD50 values, suggesting their potential as effective antiviral agents. The findings indicate that these alkaloids may support the body's defense mechanisms and reduce symptoms of COVID-19, although some properties suggest direct antiviral activity. The study highlights the promising anti-COVID-19 potential of these alkaloids, emphasizing their role in drug discovery with minimal side effects. The research underscores the importance of natural compounds in developing novel therapies for viral infections.This study evaluates the potential of natural alkaloids as therapeutic agents against SARS-CoV-2 by targeting the main protease and spike glycoprotein. The research involved docking 102 known alkaloids against these two key viral proteins, identifying six dual inhibitory compounds: liensinine, neferine, isoliensinine, fangchinoline, emetine, and acrimarine F. These compounds showed strong binding affinities, with neferine demonstrating the highest scores for both proteins. The study also assessed the stability of these compounds through molecular dynamics simulations and evaluated their ADMET properties, bioactivity scores, and drug-likeness. Neferine and emetine exhibited low toxicity and high LD50 values, suggesting their potential as effective antiviral agents. The findings indicate that these alkaloids may support the body's defense mechanisms and reduce symptoms of COVID-19, although some properties suggest direct antiviral activity. The study highlights the promising anti-COVID-19 potential of these alkaloids, emphasizing their role in drug discovery with minimal side effects. The research underscores the importance of natural compounds in developing novel therapies for viral infections.