Antiviral Activity of Vacuolar ATPase Blocker Diphyllin against SARS-CoV-2
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F21%3AN0000059" target="_blank" >RIV/00027162:_____/21:N0000059 - isvavai.cz</a>
Alternative codes found
RIV/60077344:_____/21:00555028 RIV/62156489:43210/21:43919343
Result on the web
<a href="https://www.mdpi.com/2076-2607/9/3/471" target="_blank" >https://www.mdpi.com/2076-2607/9/3/471</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/microorganisms9030471" target="_blank" >10.3390/microorganisms9030471</a>
Alternative languages
Result language
angličtina
Original language name
Antiviral Activity of Vacuolar ATPase Blocker Diphyllin against SARS-CoV-2
Original language description
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a causative agent of the pandemic coronavirus disease 2019 (COVID-19), which has resulted in over two million deaths worldwide to date. Diphyllin and diphyllinosides are known as natural blockers of cellular vacuolar ATPases, and so can act as inhibitors of the pH-dependent fusion of viral envelopes with host cell endosomal membranes. Such pH-dependent fusion is a critical early step during the SARS-CoV-2 replication cycle. Accordingly, the anti-SARS-CoV-2 profiles and cytotoxicities of diphyllin, diphyllinoside cleistanthin B, and two structurally related compounds, helioxanthin 8-1 and helioxanthin 5-4-2, are evaluated here using in vitro cell-based assay systems. Neither helioxanthin exhibits any obvious anti-SARS-CoV-2 effects in vitro. By contrast diphyllin and cleistanthin B do exhibit antiSARS-CoV-2 effects in Vero cells, with respective 50% effective concentrations (EC50) values of 1.92 and 6.51 µM. Diphyllin displays anti-SARS-CoV-2 effect also in colorectal adenocarcinoma (CaCo-2) cells. Moreover, when diphyllin is added at various times post infection, a significant decrease in viral titer is observed in SARS-CoV-2-infected Vero cells, even at high viral multiplicities of infection. Importantly, neither diphyllin nor cleistanthin B are found cytotoxic to Vero cells in concentrations up to 100 µM. However, the cytotoxic effect of diphyllin is more pronounced in Vero E6 and CaCo-2 cells. Overall, our data demonstrate that diphyllin and diphyllin analogues might be perfected as anti-SARS-CoV-2 agents in future preclinical studies, most especially if nanomedicine approaches may be invoked to optimize functional drug delivery to virus infected cells.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10607 - Virology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Microorganisms
ISSN
2076-2607
e-ISSN
2076-2607
Volume of the periodical
9
Issue of the periodical within the volume
3
Country of publishing house
CH - SWITZERLAND
Number of pages
10
Pages from-to
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UT code for WoS article
000633914200001
EID of the result in the Scopus database
2-s2.0-85101328723