Various mitigation strategies are being implemented around the world to control COVID-19. In search of broadly acting pan-specific antiviral, a team from Germany tested and proposed Influenza A virus (IAV) defective interfering particles (DIPs), which were previously used for antiviral treatment against Influenza A infections. Due o a large deletion in their genome, the IAV DIPs cannot replicate.
Also, the DIPs suppress and interfere specifically with homologous viral replication in a co-infection scenario, known as replication interference. Because of this replication interference, the IAV DIPs protect mice against an otherwise lethal IAV infection. The IAV DIPs also stimulate innate immunity rendering protection against viruses such as the influenza B virus and the pneumonia virus of mice (PVM).
The researchers tested its efficacy against SARS-CoV-2 in vitro and found the (JAK/STAT) signaling involved. To test this, they produced two promising candidate DIPs: a prototypic, well-characterized conventional IAV DIP “DI244” and a novel type of IAV DIP “OP7” containing point mutations instead of a large internal deletion in the genome using a cell culture-based production. For the in vitro studies, they used Calu-3 cells (human lung cancer cell-line) to co-infect with SARS-CoV-2 and DI244 or OP7, respectively. Both the DIPs completely inhibited the SARS-CoV-2 replication and spread in a range comparable to IFN-β or remdesivir treatment. The researchers found that the SARS-CoV-2 replication is abrogated by IAV DIP treatment in vitro. They also established that the stimulation of innate immunity causes this inhibition.
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