De novo design and synthesis of boomerang-shaped molecules and their in silico and SERS-based interactions with SARS-CoV-2 spike protein and ACE2

Amrutham, Linet Joseph Manu M.; Mambatta, Haritha Shamna K.; Varughese, Sunil Devi P. Sujatha Suresh C. H.; Maiti, Kaustabh Kumar Neogi Ishita

The recent outbreak of the COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which infects human epithelial tissue by interaction of the receptor-binding domain of its spike protein (S-protein) with angiotensin-converting enzyme 2 (ACE2). Herein, we synthesized suitably configured Tröger's bases (TB-1/2/3) and investigated molecular docking of TBs at the interface of SARS-CoV-2 S-protein and ACE2, which revealed a high docking score indicating strong binding. Detailed analysis of docking highlights strong binding of TB-2 into the interfacial domain of SARS-CoV-2 S-protein and ACE2. Furthermore, for the first time, we explored surface-enhanced Raman scattering (SERS) modality to assess intermolecular interactions between TBs and SARS-CoV-2 S-protein and ACE2.