The rapid spread of the pandemic caused by the SARS-CoV-2 virus has created an unusual situation, with rapid searches for compounds 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 which can shed light on the mechanisms of action of potential anti-COVID-19 compounds. To avoid wasting precious time and resources, we believe very stringent experimental criteria are needed in the preclinical phase, including infectivity studies with clinically isolated SARS-CoV-2, before moving on to (futile) clinical trials.

Doxycycline inhibition of a pseudotyped virus transduction does not translate to inhibition of sars-cov-2 infectivity / Diomede, L.; Baroni, S.; De Luigi, A.; Piotti, A.; Lucchetti, J.; Fracasso, C.; Russo, L.; Bonaldo, V.; Panini, N.; Filippini, F.; Fiordaliso, F.; Corbelli, A.; Beeg, M.; Pizzato, M.; Caccuri, F.; Gobbi, M.; Biasini, E.; Caruso, A.; Salmona, M.. - In: VIRUSES. - ISSN 1999-4915. - 13:9(2021), p. 1745. [10.3390/v13091745]

Doxycycline inhibition of a pseudotyped virus transduction does not translate to inhibition of sars-cov-2 infectivity

Bonaldo V.;Biasini E.;Caruso A.;
2021-01-01

Abstract

The rapid spread of the pandemic caused by the SARS-CoV-2 virus has created an unusual situation, with rapid searches for compounds 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 which can shed light on the mechanisms of action of potential anti-COVID-19 compounds. To avoid wasting precious time and resources, we believe very stringent experimental criteria are needed in the preclinical phase, including infectivity studies with clinically isolated SARS-CoV-2, before moving on to (futile) clinical trials.
2021
9
Diomede, L.; Baroni, S.; De Luigi, A.; Piotti, A.; Lucchetti, J.; Fracasso, C.; Russo, L.; Bonaldo, V.; Panini, N.; Filippini, F.; Fiordaliso, F.; Cor...espandi
Doxycycline inhibition of a pseudotyped virus transduction does not translate to inhibition of sars-cov-2 infectivity / Diomede, L.; Baroni, S.; De Luigi, A.; Piotti, A.; Lucchetti, J.; Fracasso, C.; Russo, L.; Bonaldo, V.; Panini, N.; Filippini, F.; Fiordaliso, F.; Corbelli, A.; Beeg, M.; Pizzato, M.; Caccuri, F.; Gobbi, M.; Biasini, E.; Caruso, A.; Salmona, M.. - In: VIRUSES. - ISSN 1999-4915. - 13:9(2021), p. 1745. [10.3390/v13091745]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/320553
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 5
social impact