Testing of the inhibitory effects of loratadine and desloratadine on SARS-CoV-2 spike pseudotyped virus viropexis
Yajing Hou, Shuai Ge, Xiaowei Li, Cheng Wang, Huaizhen He, Langchong He
Chemico-Biological Interactions, doi:10.1016/j.cbi.2021.109420
Currently, there is an urgent need to find a treatment for the highly infectious coronavirus disease . However, the development of a new, effective, and safe vaccine or drug often requires years and poses great risks. At this critical stage, there is an advantage in using existing clinically approved drugs to treat COVID-19. In this study, in vitro severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike pseudotyped viral infection experiments indicated that histamine H 1 antagonists loratadine (LOR) and desloratadine (DES) could prevent entry of the pseudotyped virus into ACE2-overexpressing HEK293T cells and showed that DES was more effective. Further binding experiments using cell membrane chromatography and surface plasmon resonance demonstrated that both antagonists could bind to ACE2 and that the binding affinity of DES was much stronger than that of LOR. Molecular docking results elucidated that LOR and DES could bind to ACE2 on the interface of the SARS-CoV-2-binding area. Additionally, DES could form one hydrogen bond with LYS31 but LOR binding relied on non-hydrogen bonds. To our knowledge, this study is the first to demonstrate the inhibitory effect of LOR and DES on SARS-CoV-2 spike pseudotyped virus viropexis by blocking spike protein-ACE2 interaction. This study may provide a new strategy for finding an effective therapeutic option for COVID-19.
Author statement Yajing Hou: Conceptualization, Formal analysis, Writing -original draft Data curation. Shuai Ge: Conceptualization, Formal analysis, Writing -original draft. Xiaowei Li: Formal analysis, Data curation. Cheng Wang: Data curation. Huaizhen He: Data curation. Langchong He: Supervision, Funding acquisition, Writing -review and editing.
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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