Published in J Clin Immunol: Persistence of abnormalities in the blood of convalescent COVID-19 patients until 6 months after hospital discharge

The CARE partner Inserm-VRI (France), in collaboration with the Centre Hospitalier Universitaire Vaudois (CHUV, Switzerland) has found persistent abnormalities in the blood of convalescent severe COVID-19 subjects up to six months after leaving the hospital, compared to healthy subkects. These include elevated markers of inflammation, endothelial activation and intestinal damages, as well as high levels of activated immune cells, and decreased antibodies against the virus. The findings suggest long-term impacts on the immune system even after recovery from a severe COVID-19.

In addition, there is a persistent upregulation of genes related to blood clotting. A “core gene signature” associated with a history of thrombotic events was identified in a subgroup of convalescent COVID-19 patients, with upregulation of a set of genes involved in neutrophil activation and blood coagulation. These results suggest the persistence of activation of neutrophils and disturbance of the coagulation pathway in many convalescent severe COVID-19 patients.

The lack of restoration of gene expression and immune system to a normal profile after up to 6 months of follow-up, even in asymptomatic patients who experienced severe COVID-19, indicates the need to carefully extend their clinical follow-up and propose preventive measures.

To learn more, click here: Neutrophil Activation and Immune Thrombosis Profiles Persist in Convalescent COVID-19.

Published in Microorganisms: Z-Tyr-Ala-CHN2, a Cathepsin L Inhibitor with Broad-Spectrum Cell-Specific Activity against Coronaviruses

The CARE partner Janssen Pharmaceutica in collaboration with University Utrecht, KU Leuven and Goethe University Frankfurt has published a paper about the discovery of a small molecule, Z-Tyr-Ala-CHN2, which was identified in a cell-based antiviral screen. The molecule exerts sub-micromolar antiviral activity against SARS-CoV-2, SARS-CoV-1, and human coronavirus 229E at the early phase of the infection cycle, which is in line with the observation that the molecule inhibits cathepsin L. The activity profile of Z-Tyr-Ala-CHN2 makes it an interesting tool compound for studying the biology of coronavirus entry and replication.

To learn more, click here: Identification of Z-Tyr-Ala-CHN2, a Cathepsin L Inhibitor with Broad-Spectrum Cell-Specific Activity against Coronaviruses, including SARS-CoV-2

CARE presentation at 19^th Annual PEGS Boston conference and expo

Are you going to the 19th Annual PEGS Boston conference & Expo: The Essential Protein Engineering and Cell Therapy Summit next week? If so, you will have the opportunity to discover how to identify pre-lead antibodies that have multiple epitopes on the SARS-CoV-2 spike protein using Carterra’s high-throughput epitope binning. Do not hesitate to visit the poster by CARE partner Takeda during one of the Poster Viewing session.

Title of the presentation: Identification of Binning Diversity and Binding Properties of SARS-CoV-2 Antibodies Using Carterra

Presenter: Hazal B. Kose, Ruiyang Xuee

Published in Antiviral Res: A VeroE6 cell line not requiring Pgp inhibitors to evaluate SARS-CoV-2 antivirals

Cell culture virus replication systems are essential for the study of virus replication and pathogenesis, antiviral drug testing, and virus research. Vero cells are one of the cell lines used for drug discovery as they are susceptible to SARS-CoV-2 infection – as well as to SARS-CoV-1 and MERS viruses -, easy to maintain, offer high levels of infectivity, and support efficient SARS-CoV-2 replication and virus production.

However, Vero cells express high levels of multidrug resistance protein 1 (MDR1), also named Pgp (P-glycoprotein), an ATP-dependent efflux pump, which necessitates the inclusion of a Pgp inhibitor in the cell culture to prevent tested compounds from being exported out of cells, affecting the antiviral activity as well as interpretation of data. To address this, CARE partner Pfizer used gene editing technology to generate a Pgp gene knockout VeroE6 cell line.

The VeroE6-Pgp-KO cells no longer expressed the Pgp protein and show significantly reduced efflux transporter activity. When remdesivir and nirmatrevil, two known Pgp substrates, were tested in this cell line, both drugs showed antiviral activities similar to that observed in the presence of the Pgp inhibitor.

This newly established VeroE6-Pgp-KO cell line adds a new in vitro virus infection system for SARS-CoV-2 – and possibly other viruses – to test antiviral therapies without a need to control the Pgp activity, and thus with less data variation and failed assays.

To learn more, click here: Generation of a VeroE6 Pgp gene knock out cell line and its use in SARS-CoV-2 antiviral study

Published in iScience: A new  optimized SARS-CoV-2 phenotypic screening platform

The CARE partner Goethe University Frankfurt Institute of Medical Virology, published a paper reporting on a novel phenotypic screening platform for the identification of drug candidates with activity against SARS-CoV-2 and other coronaviruses. This successful proof of concept was based on the determination of caspase 3/7 activity using the one-step Caspase-Glo 3/7 Assay System as readout. This platform uses the Caco-2-F03 cell line which demonstrated susceptibility to a broad range of SARS-CoV-2 without being affected by phospholipidosis, a known cause of false-positive hits, and is also considered suitable for neutralisation assays and phenotypic resistance testing.

To learn more, click here: Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform