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SCICONS anti-dsRNA antibody in the fight against COVID-19
SCICONS’ mouse anti double-stranded RNA antibody (clone J2) was used in crucial research to identify potent therapeutic agents to impede SARS-CoV-2 viral entry into host cells.
SARS-CoV-2, better known as COVID-19, is a positive-strand RNA virus. Positive-strand RNA viruses are a group of positive-sense, single-stranded RNA (ssRNA) viruses which include Hepatitis C, Dengue Virus, MERS and West Nile Virus. It was demonstrated in a paper by Weber et al in 20061 that cells infected by this group of viruses contain detectable levels of double-stranded RNA (dsRNA), produced as an intermediate during viral replication. It is this intermediate form which is detected by the SCICONS J2 antibody, enabling confirmation of viral infection and replication within a host cell.
The aim of a joint study between institutes based in Canada and the USA, was to identify new host-directed therapeutics preventing viral entry, by targeting the type-II transmembrane serine protease (TTSP), TMPRSS2. TMPRSS2 is a protease which mediates cleavage of the COVID-19 spike protein, a necessary step by which the pathogen gains entry via angiotensin-converting enzyme 2 (ACE2), which acts as its receptor. In this study, available as a preprint and currently under peer review, the J2 clone was used to examine the potency of anti-viral compounds by their ability to obstruct viral entry into the host cell, thus preventing infection. The authors, Shapira et al2, developed a library of novel small-molecule TMPRSS2 inhibitors as potential therapeutics. In experiments using the J2 antibody, a lung epithelial cell line (Calu-3) and a human biopsy-derived colonoid monolayer were pre-treated with therapeutic agent, followed by infection with multiple strains of SARS-CoV-2. Successful COVID-19 infection was determined by immunofluorescent cell staining of fixed cells to detect the presence of dsRNA (J2 clone) and nucleocapsid protein. From this fluorescent staining they were able to determine the percentage reduction in infection for their library of compounds. Dose response analysis and further investigations revealed compound N-0385 to be a nanomolar, broad-spectrum coronavirus inhibitor of SARS-CoV-2, including variants of concern B.1.1.7 (UK) and B.1.351 (South Africa). Their striking data in a K18-human ACE2 transgenic mouse model of SARS-CoV-2 disease demonstrated that intranasal administration of compound N-0385 early in infection improved clinical outcomes and led to a 100% survival rate compared to 20% in the control group.
The J2 anti-dsRNA IgG2a monoclonal antibody has become the gold standard in dsRNA detection. It can be used to detect dsRNA intermediates of viruses as diverse as Hepatitis C virus, Dengue virus, rhinovirus, Chikungunya virus, Rabies virus, Polio virus, Classic swine fever virus, Brome mosaic virus and many more in cultured cells, and also in fixed paraffin-embedded histological samples.
- F. Weber, V. Wagner, S. B. Rasmussen, R. Hartmann, S. R. Paludan. Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. J Virol (2006), 80(10):5059-64.
- Tirosh Shapira, I. Abrrey Monreal, Sébastien P. Dion, Mason Jager, Antoine Désilets, Andrea D. Olmstead, Thierry Vandal, David W. Buchholz, Brian Imbiakha, Guang Gao, Aaleigha Chin, William D. Rees, Theodore Steiner, Ivan Robert Nabi, Eric Marsault, Julie Sahler, Avery August, Gerlinde Van de Walle, Gary R. Whittaker, Pierre-Luc Boudreault, Hector C. Aguilar, Richard Leduc, François Jean. A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-CoV-2 variants of concern and is broadly protective against infection and mortality in mice. bioRxiv 2021.05.03.442520; doi: https://doi.org/10.1101/2021.05.03.442520
This article is a preprint and has not been certified by peer review