Binding Assays of Drug and Biological Molecule for Screening Drug Repositioning Candidates as Therapeutic Option against Emerging Infectious Diseases

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative viral pathogen in the coronavirus disease 2019 (COVID-19) pandemic, which prompted an immediate global response to the development of vaccines and antiviral therapeutics. Drug repurposing in antiviral therapeutics allows for the rapid advancement of existing clinical candidates and therapies into human clinical trials to be tested as COVID-19 therapies. Screening method for drug repurposing are required to prepare the next emerging infectious diseases. In the present study, surface plasmon resonance imaging (SPRi) technique was used to find drug repositioning candidates by taking SARS-CoV2 as an example. Preventing viral entry is an effective antiviral treatment strategy used early during symptom onset. SARS-CoV-2 enters angiotensin-converting enzyme 2 (ACE2)-expressing cells when the receptor-binding domain of the spike protein on the surface of SARS-CoV-2 binds to ACE2, followed by cleavage at two cut sites by transmembrane protease, serine 2 (TMPRSS2). Therefore, a molecule capable of inhibiting the protease activity of TMPRSS2 could be a valuable antiviral therapy. We evaluated whether it was possible to detect specific binding by measuring interactions of drugs and TMPRSS2. In a result, ulinastatin bound with recombinant TMPRSS2 immobilized on biochips pH-dependently. These results suggested that SPRi can be useful technique to discover drug repositioning candidates without in vitro assay, which contributes to the rapid screening.