Doxycycline inhibition of a pseudotyped virus transduction does not translate to inhibition of SARS-CoV-2 infectivity Article Swipe
Luisa Diomede
,
Sara Baroni
,
Ada De Luigi
,
Arianna Piotti
,
Jacopo Lucchetti
,
Claudia Fracasso
,
Luca Russo
,
Valerio Bonaldo
,
Nicolò Panini
,
Federica Filippini
,
Fabio Fiordaliso
,
Alessandro Corbelli
,
Marten Beeg
,
Massimo Pizzato
,
Francesca Caccuri
,
Marco Gobbi
,
Emiliano Biasini
,
Arnaldo Caruso
,
Mario Salmona
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.07.30.454436
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.07.30.454436
The pandemic caused by the SARS-CoV-2 has created the need of compounds able to interfere with the biological processes exploited by the virus. Doxycycline, with its pleiotropic effects, including anti-viral activity, has been proposed as a therapeutic candidate for COVID-19 and about twenty clinical trials have started since the beginning of the pandemic. To gain information on the activity of doxycycline against SARS-CoV-2 infection and clarify some of the conflicting clinical data published, we designed in vitro binding tests and infection studies with a pseudotyped virus expressing the spike protein, as well as a clinically isolated SARS-CoV-2 strain. Doxycycline inhibited the transduction of the pseudotyped virus in Vero E6 and HEK-293 T cells stably expressing human receptor angiotensin-converting enzyme 2 but did not affect the entry and replication of SARS-CoV-2. Although this conclusion is apparently disappointing, it is paradigmatic of an experimental approach aimed at developing an integrated multidisciplinary platform. To avoid wasting precious time and resources we believe very stringent experimental criteria are needed in the preclinical phase, including infectious studies with SARS-CoV-2 in the platform before moving on to [failed] clinical trials. Author Summary The pandemic caused by the SARS-CoV-2 virus has created a completely unusual situation in rapidly searching for compounds able to interfere with the biological processes exploited by the virus. This new scenario has substantially changed the timing of drug development which has also resulted in the generation of controversial results, proving that the transition from computational screening to the clinical application requires great caution and careful studies. It is therefore necessary to establish new paradigms for evaluating the efficacy of a potential active molecule. We set up a preclinical platform aimed at identifying molecules active against SARS-CoV-2 infection developing a multidisciplinary approach based on very stringent experimental criteria, comprising in-silico studies, in vitro binding tests and infection studies with pseudovirus expressing the spike protein as well as clinically isolated SARS-CoV-2 strains. We focused our attention on doxycycline which has been suggested as potential therapeutic candidate for treating COVID-19 and is currently employed in about twenty clinical trials. Doxycycline resulted effective in inhibiting the transduction of pseudovirus but it did not affect the entry and replication of SARS-CoV-2. The results obtained underline the need to define more stringent and controlled pharmacological approaches before wasting precious time and resources with clinical trials.
Related Topics
Concepts
Doxycycline
Virus
Virology
Pandemic
Viral entry
Biology
Infectivity
Clinical trial
Viral replication
Coronavirus
Vero cell
Coronaviridae
Medicine
Coronavirus disease 2019 (COVID-19)
Bioinformatics
Infectious disease (medical specialty)
Antibiotics
Microbiology
Disease
Internal medicine
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2021.07.30.454436
- https://www.biorxiv.org/content/biorxiv/early/2021/07/30/2021.07.30.454436.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 30
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3187292573
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3187292573Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2021.07.30.454436Digital Object Identifier
- Title
-
Doxycycline inhibition of a pseudotyped virus transduction does not translate to inhibition of SARS-CoV-2 infectivityWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-07-30Full publication date if available
- Authors
-
Luisa Diomede, Sara Baroni, Ada De Luigi, Arianna Piotti, Jacopo Lucchetti, Claudia Fracasso, Luca Russo, Valerio Bonaldo, Nicolò Panini, Federica Filippini, Fabio Fiordaliso, Alessandro Corbelli, Marten Beeg, Massimo Pizzato, Francesca Caccuri, Marco Gobbi, Emiliano Biasini, Arnaldo Caruso, Mario SalmonaList of authors in order
- Landing page
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https://doi.org/10.1101/2021.07.30.454436Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2021/07/30/2021.07.30.454436.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2021/07/30/2021.07.30.454436.full.pdfDirect OA link when available
- Concepts
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Doxycycline, Virus, Virology, Pandemic, Viral entry, Biology, Infectivity, Clinical trial, Viral replication, Coronavirus, Vero cell, Coronaviridae, Medicine, Coronavirus disease 2019 (COVID-19), Bioinformatics, Infectious disease (medical specialty), Antibiotics, Microbiology, Disease, Internal medicineTop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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2023: 1Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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