Background
In December 2019, cases of an acute respiratory disease were reported from Wuhan, the capital of Hubei province in China. The number of infections increased rapidly and spread to other areas of China and on January 13th, 2020, the first case was reported outside of China. The causative agent was identified as a novel coronavirus (CoV) of the lineage b of the genus Betacoronavirus that also includes the 2002 SARS-CoV that caused a global outbreak of severe acute respiratory syndrome (SARS) in 2002 and 2003. The newly-emerged CoV was named SARS-CoV-2 by the World Health Organization (WHO) in February 2020, and the outbreak was declared a pandemic on March 11th, 2020. The respiratory disease caused by SARS-CoV-2 was named coronavirus 2019 disease (COVID-19).
Technology Description
This invention and licensing opportunity relate to steric blocking antisense oligomers useful for treating or preventing a SARS-CoV-2 infection and COVID‑19. The antisense oligomers target the SARS-CoV-2 genomic RNA, specifically the 5’ untranslated region (5’UTR) and first 20 nucleotides of coding sequence for the 1a/b polyprotein.
Five PPMOs targeted against various sites in the genomic RNA of SARS-CoV-2, along with a negative control PPMO, were evaluated for their ability to suppress virus growth in cell cultures. Each PPMO was tested for its effect on the viability of uninfected cells and its inhibitory effect on the replication of SARS-CoV-2 in Vero cell cultures. Cell viability was evaluated with an ATP-based method and viral growth was measured with quantitative RT-PCR and TCID50 infectivity assays. In cell viability assays, cells treated with PPMO at the concentrations used in the antiviral assays described below for 48 hours showed no loss of viability. In the antiviral assays, cells were treated with 4, 8 or 16 µM PPMO for 5 hours, then infected and further incubated without PPMO. The cells were assayed for viral titer at various time points post-infection. Four of the five PPMOs were highly efficacious, reducing viral titers by up to 4-6 log10 at 48-72 hours post-infection, in a non-toxic and dose-responsive manner. The data indicate that PPMOs can potently and specifically suppress SARS-CoV-2 growth and are promising candidates for further pre-clinical development.
Features & Benefits
Antisense oligomers provide an alternative therapeutic approach to the prevention and treatment of SARS‑CoV‑2 and COVID‑19.
Applications
Status
PCT/US2021/031335
U.S. non-provisional patent application No. 18/053,308