Selecting a stable solid form of remdesivir using microcrystal electron diffraction and crystal structure prediction
Sivakumar Sekharan, Xuetao Liu, Zhuocen Yang, Xiang Liu, Li Deng, Shigang Ruan, Yuriy A. Abramov, Guangxu Sun, Sizhu Li, Tian Zhou, Baime Shi, Qun Zeng, Qiao Zeng, Chao Chang, Yingdi Jin, Xuekun Shi
Abstract
Therapeutic options in response to the coronavirus disease 2019 (COVID-19) outbreak are urgently needed. In this communication, we demonstrate how to support selection of a stable solid form of an antiviral drug remdesivir in quick time using the microcrystal electron diffraction (MicroED) technique and a cloud-based and artificial intelligence implemented crystal structure prediction platform. We present the MicroED structures of remdesivir forms II and IV and conclude that form II is more stable than form IV at ambient temperature in agreement with experimental observations. The combined experimental and theoretical study can serve as a template for formulation scientists in the pharmaceutical industry.