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bioRxiv · 10.1101/2021.08.25.457645

Structure-based screening of drug candidates targeting the SARS-CoV-2 envelope protein

Xia, X.·Zhang, Y.·Li, S.·Lin, H.·Yan, Z.
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Abstract

The COVID-19 (coronavirus disease 2019) pandemic is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). SARS-CoV-2 produces a small hydrophobic envelope (E) protein which shares high homology with SARS-CoV E protein. By patch-clamp recording, the E protein is demonstrated to be a cation-selective ion channel. Furthermore, the SARS-CoV-2 E protein can be blocked by a SARS-CoV E protein inhibitor hexamethylene amiloride. Using structural model and virtual screening, another E protein inhibitor AZD5153 is discovered. AZD5153 is a bromodomain protein 4 inhibitor against hematologic malignancies in clinical trial. The E protein amino acids Phe23 and Val29 are key determinants for AZD5153 sensitivity. This study provides two promising lead compounds and a functional assay of SARS-CoV-2 E protein for the future drug candidate discovery.

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Xia, X., Zhang, Y., Li, S., Lin, H., Yan, Z.. 2021-08-25. Structure-based screening of drug candidates targeting the SARS-CoV-2 envelope protein. https://doi.org/10.1101/2021.08.25.457645

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