Journal
CRYSTALS
Volume 11, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/cryst11121579
Keywords
SARS-CoV-2; main protease; serial femtosecond crystallography; high-throughput drug screening
Funding
- National Science Foundation (NSF) Science and Technology Centers grant [NSF-1231306]
- 2232 International Fellowship for Outstanding Researchers Program
- 2244 Industrial PhD Fellowship Program
- 1001 Scientific and Technological Research Projects Funding Program of the Scientific and Technological Research Council of Turkey (TUEBITAK) [118C270, 119C132, 120Z520]
- TUEBITAK
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]
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Global investigation into COVID-19 since early 2020 aiming to characterize the virus and develop vaccines. Drug repurposing studies conducted with a focus on in silico drug screening for efficiency. Utilization of advanced technology for high-throughput drug screening with X-ray Free-Electron Laser (XFEL) for remote data collection at ambient temperature.
Since early 2020, COVID-19 has grown to affect the lives of billions globally. A worldwide investigation has been ongoing for characterizing the virus and also for finding an effective drug and developing vaccines. As time has been of the essence, a crucial part of this research has been drug repurposing; therefore, confirmation of in silico drug screening studies have been carried out for this purpose. Here we demonstrated the possibility of screening a variety of drugs efficiently by leveraging a high data collection rate of 120 images/second with the new low-noise, high dynamic range ePix10k2M Pixel Array Detector installed at the Macromolecular Femtosecond Crystallography (MFX) instrument at the Linac Coherent Light Source (LCLS). The X-ray Free-Electron Laser (XFEL) is used for remote high-throughput data collection for drug repurposing of the main protease (Mpro) of SARS-CoV-2 at ambient temperature with mitigated X-ray radiation damage. We obtained multiple structures soaked with nine drug candidate molecules in two crystal forms. Although our drug binding attempts failed, we successfully established a high-throughput Serial Femtosecond X-ray crystallographic (SFX) data collection protocol.
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