RT Journal Article
SR Electronic
T1 Case Study of High-Throughput Drug Screening and Remote Data Collection for SARS-CoV-2 Main Protease by Using Serial Femtosecond X-ray Crystallography
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.28.468932
DO 10.1101/2021.11.28.468932
A1 Omur Guven
A1 Mehmet Gul
A1 Esra Ayan
A1 J. Austin Johnson
A1 Baris Cakilkaya
A1 Gozde Usta
A1 Fatma Betul Ertem
A1 Nurettin Tokay
A1 Busra Yuksel
A1 Oktay Gocenler
A1 Cengizhan Buyukdag
A1 Sabine Botha
A1 Gihan Ketawala
A1 Zhen Su
A1 Brandon Hayes
A1 Frederic Poitevin
A1 Alexander Batyuk
A1 Chun Hong Yoon
A1 Christopher Kupitz
A1 Serdar Durdagi
A1 Raymond G. Sierra
A1 Hasan DeMirci
YR 2021
UL http://biorxiv.org/content/early/2021/11/30/2021.11.28.468932.abstract
AB 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 has 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 9 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.Competing Interest StatementThe authors have declared no competing interest.