Near-Physiological-Temperature Serial Crystallography Reveals Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing. Durdagi et al

Research to identify effective therapies for COVID-19 includes: i) designing a vaccine as future protection; ii) de novo drug discovery; and iii) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determine two apo structures of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) main protease at ambient-temperature by Serial Femtosecond X-ray crystallography.

We employ detailed molecular simulations of selected known main protease inhibitors with the structures and compare binding modes and energies. The combined structural and molecular modeling studies not only reveal the dynamics of small molecules targeting the main protease but also provide invaluable opportunities for drug repurposing and structure-based drug design strategies against SARS-CoV-2.