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Testing of the inhibitory effects of loratadine and desloratadine on SARS-CoV-2 spike pseudotyped virus viropexis

Hou et al., Chemico-Biological Interactions, doi:10.1016/j.cbi.2021.109420
Apr 2021  
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10th treatment shown to reduce risk in December 2020
 
*, now with p = 0.00006 from 15 studies.
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No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 81 treatments. c19early.org
In Vitro study showing that histamine H1 antagonists loratadine (LOR) and desloratadine (DES) inhibit SARS-CoV-2 spike pseudovirus entry into ACE2-overexpressing HEK293T cells, with DES showing greater efficacy. Using cell membrane chromatography and surface plasmon resonance, authors demonstrate that both LOR and DES bind to ACE2, with DES having a much higher binding affinity. Molecular docking suggests LOR and DES bind ACE2 at the SARS-CoV-2 spike protein binding interface, with DES forming a hydrogen bond with LYS31 while LOR relies on non-hydrogen bonding. This hydrogen bond may enable DES to block the interaction between the SARS-CoV-2 receptor binding domain and ACE2. The results suggest DES may be a more effective treatment for COVID-19 than LOR by preventing viral entry.
11 preclinical studies support the efficacy of antihistamine H1RAs for COVID-19:
Hou et al., 30 Apr 2021, China, peer-reviewed, 6 authors. Contact: helc@mail.xjtu.edu.cn.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperH1RAsAll
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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