Trimerbody based therapies for COVID-19: targeting SARS-CoV-2 viral entry mechanism by next-gen trimeric Spikebodies

22-04-2020

The novel coronavirus SARS-CoV-2 has recently emerged as a human pathogen in China, causing fever, severe respiratory illness, and pneumonia a disease recently named coronavirus disease 19 (COVID-19). With over 2,600,000 confirmed cases to date, this pandemic continues to expand, however, there is no specific antiviral treatment or vaccine currently available and the standard of care is limited to palliative therapy. Therefore, there is an urgent need to develop and provision of therapies for pre-exposure prophylaxis or post-exposure treatment.

Coronavirus entry into host cells binding to angiotensin-converting enzyme 2 (ACE2) via the receptor binding domain (RBD) of the transmembrane spike (S) glycoprotein that forms homotrimers protruding from the viral surface (Figure 1). Disrupting the SARS-CoV-2-RBD binding to ACE2 with designer drugs has the potential to inhibit the virus from entering human cells, presenting a new modality for therapeutic intervention.

Recently, several peptide-based binders have recently been reported to efficiently inhibit the RBD-ACE2 interaction. Leadartis (Figure 2) in collaboration with Dr Alvarez-Vallina's lab at the “imas12 Biomedical Research Institute” (https://imas12.es/en/research/cancer/immuno-oncology-and-immunotherapy-g...) is developing new next-gen trimeric SARS-CoV-2-RBD blockers, using the trimerbody technology platform (Figure 1). Because of its configuration, avidity and pharmacokinetics the spike-blocker homotrimeric antibody-like molecules (termed Spikebodies) might have important advantages over conventional peptide-based binders. Spikebodies provides new avenues for COVID-19 treatment blocking the SARS-CoV-2 spike protein  interaction with ACE2 and thus precluding virus entry into human cells.

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