Three kinds of treatment with Homoharringtonine, Hydroxychloroquine or shRNA and their combination against coronavirus PEDV in vitro

Li, Cuicui; Wang, Xiao-Jia

doi:10.1186/s12985-020-01342-w

Cited by 9 publications

(5 citation statements)

References 38 publications

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“…As three compound descriptors (pI, dLogD, and tpsaEfficiency) were intimately linked to the biological activity of SARS-CoV-2-inhibitory lysosomotropic agents, we decided to investigate their status among 39 other drugs, chosen for their documented capacity to modulate the SARS-CoV-2 effect. Thus, we used the insights obtained above to classify agents that have been published to inhibit SARS-CoV-2 replication such as three α-ketoamide inhibitors 13 , abiratone 14 , azithromycin 15 , bexarotene 14 , β-d-N4-hydroxycytidine (NHC; EIDD-1931) 16 , camostat mesylate 17 , cepharanthine 18 , cetilistat 14 , chloroquine 19 , chlorpromazine: 20 , diiodohydroxyquinoline 14 , emetine 21 , homoharringtonine (also called omacetaxine mepesuccinate) 21 , 22 , ivermectin 23 ; lopinavir 21 , mefloquine 18 , remdesivir 21 , and selamectin 18 .…”

Section: Resultsmentioning

confidence: 99%

On-target versus off-target effects of drugs inhibiting the replication of SARS-CoV-2

et al. 2020

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The current epidemic of coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) calls for the development of inhibitors of viral replication. Here, we performed a bioinformatic analysis of published and purported SARS-CoV-2 antivirals including imatinib mesylate that we found to suppress SARS-CoV-2 replication on Vero E6 cells and that, according to the published literature on other coronaviruses is likely to act ontarget, as a tyrosine kinase inhibitor. We identified a cluster of SARS-CoV-2 antivirals with characteristics of lysosomotropic agents, meaning that they are lipophilic weak bases capable of penetrating into cells. These agents include cepharentine, chloroquine, chlorpromazine, clemastine, cloperastine, emetine, hydroxychloroquine, haloperidol, ML240, PB28, ponatinib, siramesine, and zotatifin (eFT226) all of which are likely to inhibit SARS-CoV-2 replication by non-specific (off-target) effects, meaning that they probably do not act on their 'official' pharmacological targets, but rather interfere with viral replication through non-specific effects on acidophilic organelles including autophagosomes, endosomes, and lysosomes. Imatinib mesylate did not fall into this cluster. In conclusion, we propose a tentative classification of SARS-CoV-2 antivirals into specific (on-target) versus non-specific (off-target) agents based on their physicochemical characteristics.

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Section: Resultsmentioning

confidence: 99%

On-target versus off-target effects of drugs inhibiting the replication of SARS-CoV-2

et al. 2020

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“…Porcine epidemic diarrhea virus (PEDV) strain CV777 was reproduced in Vero cells [ 12 ]. PEDV titers were determined by a 50% tissue culture infective dose (TCID 50 ) assay in Vero cells [ 13 ]. Anti PEDV-N (1:1000) mouse monoclonal antibody was obtained from Alpha Diagnostic International (San Antonio, TX, USA).…”

Section: Methodsmentioning

confidence: 99%

Small-Molecule RAF265 as an Antiviral Therapy Acts against PEDV Infection

Wang

Tian

et al. 2022

Viruses

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Porcine epidemic diarrhea virus (PEDV), a member of the family Coronaviridae, causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, and has caused significant economic losses in the pig industry. There are currently no specific drugs available to treat PEDV. Viruses depend exclusively on the cellular machinery to ensure an efficient replication cycle. In the present study, we found that small-molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of RAF, reduced viral loads of PEDV by 4 orders of magnitude in Vero cells, and protected piglets from virus challenge. RAF265 reduced PEDV production by mediating cytoskeleton arrangement and targeting the host cell’s translation machinery. Treatment with RAF265 inhibited viral entry of PEDV S-glycoprotein pseudotyped viral vector particle (PEDV-pp), at half maximal effective concentrations (EC50) of 79.1 nM. RAF265 also presented potent inhibitory activity against viral infection by SARS-CoV-2-pp and SARS-CoV-pp. The present work may provide a starting point for further progress toward the development of antiviral strategies effective against coronavirus PEDV.

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“…Homoharringtonine was known to inhibit mouse hepatitis coronavirus (MHV) translation in vitro in 125 nmol/L dose. eIF4E phosphorylation promotes replication and translation of MHV which is downregulated by homoharringtonine [157]. In another study with PEDV in Vero E6 cell line, homoharringtonine at doses of 150 nmol/L and 300 nmol/L reduced viral titer by 3.5-fold and 40-fold, respectively, in the 50% tissue culture infectious dose (TCID50) [158].…”

Section: Homoharringtoninementioning

confidence: 99%

Phytochemicals for mitigating the COVID-19 crisis: evidence from pre-clinical and clinical studies

Das,

Khan,

Roy

et al. 2023

Explor Drug Sci

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The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019 quickly escalated to pandemic levels and had a severe impact on public health. There are 761 million confirmed coronavirus disease 2019 (COVID-19) cases, with over 6.88 million deaths worldwide till March 2023. Severe cases of the disease caused critical respiratory failure followed by multiorgan involvement. Clinical escalation of COVID-19 has been correlated with markedly increased plasma inflammatory markers [e.g., C-reactive protein (CRP)] and pro-inflammatory cytokine levels [e.g., interleukin (IL)-6, tumor necrosis factor-α (TNF-α)]. Therapeutic options have mostly utilized corticosteroids, antivirals (e.g., remdesivir), and monoclonal antibody-based immunomodulation (e.g., tocilizumab). These existing treatments have adverse side effects, inadequate efficacy, and limitations in administering to patients with comorbidities and other underlying diseases. Monoclonal antibody-based therapies and some of the antivirals are very costly. Many phytochemicals have previously reported anti-inflammatory, antiviral, and antioxidant properties. Studying the effectiveness of such phytochemicals against COVID-19 and identifying new plant-derived molecules with antiviral properties have been a focus since the SARS-CoV-2 outbreak. This review article has documented in vitro, in vivo, and clinical studies encompassing 28 different phytochemicals belonging to various chemical groups (e.g., polyphenols, alkaloids, terpenes) that show anti-COVID-19 activity. These findings suggest that multiple phytochemicals can interfere with virus entry and replication inside the host cell. Many of them can protect from cytokine storm by acting on intracellular signalling pathways in addition to inhibiting virus multiplication. Phytochemicals may prove useful in alleviating post-COVID complications associated with kidney injury, and central nervous system complications, as well. Plant-derived compounds are usually cheaper and have fewer side effects. But, developing new formulations with better absorption and bioavailability remains a priority. This review informs the readers of the current status and indicates the ongoing research in this highly relevant field.

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Three kinds of treatment with Homoharringtonine, Hydroxychloroquine or shRNA and their combination against coronavirus PEDV in vitro

Cited by 9 publications

References 38 publications

On-target versus off-target effects of drugs inhibiting the replication of SARS-CoV-2

On-target versus off-target effects of drugs inhibiting the replication of SARS-CoV-2

Small-Molecule RAF265 as an Antiviral Therapy Acts against PEDV Infection

Phytochemicals for mitigating the COVID-19 crisis: evidence from pre-clinical and clinical studies

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