• Project Title: Reactivity-guided design and chemical synthesis of Berberine analogs towards photodynamic treatment of cancer and high throughput virtual screening of targeted compounds towards strategic therapeutic approaches in treating SARS-CoV2

  • BASIS Advisor: Dr. Ivana Bozidarevic

  • Internship Location: Aspiring Scholars Directed Research Program

  • Onsite Mentor: Edward Njoo

In drug development and medicine, there are many different methods and strategies that can be pursued in designing novel small molecule therapeutics. One way to design pharmaceuticals is through thinking about reactivity, whether that is the reaction of a molecule with the target or possible reactions that can be done to modify the molecule. Berberine, a natural product extracted from plants in the genus Berberis, has been demonstrated to have various biological activities including and the ability to bind to DNA, antibacterial effects, cytotoxic effects, and antitumor properties. The known biological activity of berberine, along with its long history in traditional medicine and its current use as a dietary supplement marketed to individuals with type II diabetes, high blood pressure, and high cholesterol, has made it a compound of interest to medicinal and organic chemists. Synthetic modifications can be done to different carbon positions of berberine, and the products of those reactions can be screened to see if they result in more potent biological activity. Science and research responds to the current issues in society, and as the novel coronavirus pandemic, which first emerged in Wuhan, China in December of 2019, quickly spread across the globe and changed the structure of our society and daily lives, research towards the development of possible inhibitors and vaccines became of huge interest. Potential inhibitors of SARS-CoV-2 main protease, which play a role in viral replication, and the spike glycoprotein, which is essential for cellular entry, were designed based on known reactivity between the target and the compounds. Computational screening of the inhibitors developed through de novo molecular design allow us to identify compounds that may be effective against the coronavirus in humans. Methodology in the research of these two projects demonstrate how reactivity can serve as the basis of drug design.