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.
【저자키워드】 COVID-19, SARS-CoV-2, in vitro, surface plasmon resonance, Spike protein, tetracyclines, doxycycline, 【초록키워드】 clinical trial, pandemic, T cells, SARS-COV-2 infection, Infection, clinical trials, SARS-CoV-2 virus, virus, angiotensin-converting enzyme 2, Spike protein, Replication, Spread, T cell, Pseudotyped virus, transduction, therapeutic, doxycycline, receptor, anti-viral activity, information, platform, mechanism, binding, compounds, Pleiotropic effects, angiotensin, criteria, Vero E6, biological processes, Clinical data, Compound, SARS-CoV-2 strain, HEK-293, replication of SARS-CoV-2, resources, approach, caused, clinically, inhibited, the spike protein, interfere, not affect, expressing, biological processe, the SARS-CoV-2 virus, 【제목키워드】 inhibition, Infectivity, doxycycline,