Identification of SARS-CoV-2 entry inhibitors among already approved drugs

Li, Yang; Pei, Rong juan; Li, Heng; Xin, Na; Zhou, Yu; Zhu, Feng; He, Pei Lan; Tang, Wei; Zhang, Ye cheng; Xiong, Ji; Xiao, Shu; Tong, Xian kun; Zhang, Bo; Zuo, Jian

doi:10.1038/s41401-020-00556-6

Cited by 80 publications

(83 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although we did not address the mechanism of action, our data on the effect of chlorpromazine on HEK cells and Calu-1 cells are in agreement with these earlier studies. Other antipsychotics, flupenthixol and pimozide, identified as inhibitors of pseudotyped viral infection of HEK cells in our study, have also been confirmed by others as antiviral agents (Drayman et al, 2020;Yang et al, 2020). Pimozide, tested by computational docking analysis and in vitro assays, has been suggested to inhibit main protease of SARS-CoV-2 (M Pro ) (Vatansever et al, 2020).…”

Section: Discussionsupporting

confidence: 79%

“…Recently, a number of studies presented evidence supporting the effects of antidepressant drugs and related psychoactive drugs as antiviral compounds against SARS-CoV-2 (Carpinteiro et al, 2020;Drayman et al, 2020;Hoertel et al, 2021;Lenze et al, 2020;Marion Plaze et al, 2020;Schloer et al, 2020;Yang et al, 2020;Zimniak et al, 2021). One of these studies addressing SSRIs for their antiviral activity did not show any effect of escitalopram and paroxetine, while fluoxetine was successful with inducing antiviral activity after 3 days of treatment (Zimniak et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antidepressant and antipsychotic drugs reduce viral infection by SARS-CoV-2 and fluoxetine show antiviral activity against the novel variants in vitro

Fred

Kuivanen

Uğurlu

et al. 2021

Preprint

View full text Add to dashboard Cite

Background and Purpose: Repurposing of currently available drugs is a valuable strategy to tackle the consequences of COVID-19. Recently, several studies have investigated the effect of psychoactive drugs on SARS-CoV-2 in cell culture models as well as in clinical practice. Our aim was to expand these studies and test some of these compounds against newly emerged variants. Experimental Approach: Several antidepressant drugs and antipsychotic drugs with different primary mechanisms of action were tested in ACE2/TMPRSS2-expressing human embryonic kidney cells against the infection by SARS-CoV-2 spike protein-dependent pseudoviruses. Some of these compounds were also tested in human lung epithelial cell line, Calu-1, against the first wave (B.1) lineage of SARS-CoV-2 and the variants of concern, B.1.1.7 and B.1.351. Key Results: Several clinically used antidepressants, including fluoxetine, citalopram, reboxetine, imipramine, as well as antipsychotic compounds chlorpromazine, flupenthixol, and pimozide inhibited the infection by pseudotyped viruses with minimal effects on cell viability. The antiviral action of several of these drugs was verified in Calu-1 cells against the (B.1) lineage of SARS-CoV-2. By contrast, the anticonvulsant carbamazepine, and novel antidepressants ketamine and its derivatives as well as MAO and phosphodiesterase inhibitors phenelzine and rolipram, respectively, showed no activity in the pseudovirus model. Furthermore, fluoxetine remained effective against pseudo viruses with N501Y, K417N, and E484K spike mutations, and the VoC-1 (B.1.1.7) and VoC-2 (B.1.351) variants of SARS-CoV-2. Conclusion and Implications: Our study confirms previous data and extends information on the repurposing of these drugs to counteract SARS-CoV-2 infection including different variants of concern.

show abstract

Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Antidepressant and antipsychotic drugs reduce viral infection by SARS-CoV-2 and fluoxetine show antiviral activity against the novel variants in vitro

Fred

Kuivanen

Uğurlu

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“… 190 Similarly, other entry inhibitors have been identified from generic screens of approved drugs ( vide infra ), including clemastine, amiodarone, trimeprazine, busitinib, toremifene, flupenthixol, and azelastine, likely via histamine receptor antagonism. 191 Last, owing to the now established role of the integrin α5β1 as a ligand for the spike protein and for ACE2, efforts to interrupt those interactions represent another strategy for inhibiting viral entry. To this end, the integrin-binding peptide, ATN-161, has recently been shown to inhibit these critical interactions in early infection.…”

Section: Translating To Therapies For Sars-cov-2mentioning

confidence: 99%

COVID-19 and Cardiovascular Disease

Chung

Zidar

Bristow

et al. 2021

Circulation Research

293

266

View full text Add to dashboard Cite

A pandemic of historic impact, coronavirus disease 2019 (COVID-19) has potential consequences on the cardiovascular health of millions of people who survive infection worldwide. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can infect the heart, vascular tissues, and circulating cells through ACE2 (angiotensin-converting enzyme 2), the host cell receptor for the viral spike protein. Acute cardiac injury is a common extrapulmonary manifestation of COVID-19 with potential chronic consequences. This update provides a review of the clinical manifestations of cardiovascular involvement, potential direct SARS-CoV-2 and indirect immune response mechanisms impacting the cardiovascular system, and implications for the management of patients after recovery from acute COVID-19 infection.

show abstract

“…Recently, molecular docking and simulation studies have also reported that azelastine has optimal features for binding with the main protease on SARS-CoV-2 [ 28 ]. Antihistamines trimeprazine, azelastine, and clemastine have been identified as SARS-CoV-2 entry inhibitors following an antiviral test using native SARS-CoV-2 virus in Vero E6 cells [ 36 ]. This suggests that antihistamines have the potential to inhibit SARS-CoV-2 entry into cells.…”

Section: Discussionmentioning

confidence: 99%

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

Hou

et al. 2021

Chemico-Biological Interactions

View full text Add to dashboard Cite

Currently, there is an urgent need to find a treatment for the highly infectious coronavirus disease (COVID-19). 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.

show abstract

Identification of SARS-CoV-2 entry inhibitors among already approved drugs

Cited by 80 publications

References 43 publications

Antidepressant and antipsychotic drugs reduce viral infection by SARS-CoV-2 and fluoxetine show antiviral activity against the novel variants in vitro

Antidepressant and antipsychotic drugs reduce viral infection by SARS-CoV-2 and fluoxetine show antiviral activity against the novel variants in vitro

COVID-19 and Cardiovascular Disease

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

Contact Info

Product

Resources

About