Identification of Plitidepsin as Potent Inhibitor of SARS-CoV-2-Induced Cytopathic Effect after a Drug Repurposing Screen

Abstract

196)Different treatments are currently used for clinical management of SARS-CoV-2 infection, but little is known about their efficacy yet. Here we present ongoing results to compare currently available drugs for a variety of diseases to find out if they counteract SARS-CoV-2-induced cytopathic effect in vitro. Our goal is to prioritize antiviral activity to provide a solid evidence-driven rationale for forthcoming clinical trials.Since the most effective antiviral approaches are usually based on combined therapies that tackle the viral life cycle at different stages, we are also testing combinations of drugs that may be critical to reduce the emergence of resistant viruses. We will provide results as soon as they become available, so data should be interpreted with caution, clearly understanding the limitations of the in vitro model, that may not always reflect what could happen in vivo. Thus, our goal is to test the most active antivirals identified in adequate animal models infected with SARS-CoV-2, to add more information about possible in vivo efficacy. In turn, successful antivirals could be tested in clinical trials as treatments for infected patients, but also as pre-exposure prophylaxis to avoid novel infections until an effective and safe vaccine is developed.

Detection of SARS-CoV-2 in a cat owned by a COVID-19−affected patient in Spain

“…A virus neutralization assay in plasma of both C1 and C2 was performed following a previously published protocol (13).…”

Cross-Neutralization Activity Against SARS-CoV-2 is Present in Currently Available Intravenous Immunoglobulins

“…Two different SARS-CoV-2 isolates, collected from nasopharyngeal swab from COVID-19 patients, were tested: SARS-CoV-2 MAD6 isolated from a 69-year-old male patient from Madrid (Spain); and SARS-CoV-2 (accession ID EPI_ISL_418268 at GISAID repository: http://gisaid.org ) isolated from a an 89-year-old male patient from Badalona (Spain). Both stock viruses were prepared by collecting the supernatant from Vero E6 cells, as previously described [ 25 ]. Recombinant MERS-CoV was generated using a previously described reverse genetic system [ 26 ] from the reference sequence of MERS-CoV isolated from the index patient EMC/2012 (GeneBank JX869059) [ 27 ].…”

“…IC 50 values were determined from the fitted curves as the plasma dilutions that produced 50% neutralization. Details of the technique are available elsewhere [25].…”

Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins

“…Two different SARS-CoV-2 isolates were tested: a) SARS-CoV-2 MAD6 isolated from a COVID-19 patient in Spain; and b) SARS-CoV-2 (accession ID EPI_ISL_418268 at GISAID repository: http://gisaid.org) isolated from a COVID-19 patient in Spain. Both stock viruses (a and b) were prepared by collecting the supernatant from Vero E6 cells, as previously described 21 . Recombinant MERS-CoV was generated using a previously described reverse genetic system 22 from the reference sequence of MERS-CoV isolated from the index patient EMC/2012 (GeneBank JX869059) 23 .…”

“…IC50 values were determined from the fitted curves as the plasma dilutions that produced 50% neutralization. Details of the technique are available elsewhere 21 .…”