Bacteriophage-derived doublestranded RNA (Larifan) exerts anti-SARS-CoV-2 activity in vitro and in golden Syrian hamsters in vivo

Since the emergence of the COVID-19 pandemic, many efforts have been introduced to fight the virus and the consequences it may cause. Like many others, our lab rose to the challenge and utilised its knowledge to end the spread of the virus. This will not be another never-ending story about a fight between a living animal and a parasitic virus. This might be a story of success. For some time, our lab has studied this antiviral medication, commonly known as Larifan, which promotes the immune system to protect it from viruses. Larifan consists of naturally obtained double-stranded (ds) ribonucleic acid (RNA) strains. Usually, all living things have RNA in the form of single strands. However, viruses, during their replication cycle, can have a dsRNA stage, which is quickly recognised by our immune system. Evolutionally, special receptors have been developed to sense and identify such “unnatural” forms of RNA. Upon encounter, our immune cells get to work and produce signalling molecules that can fight the virus, also known as cytokines, particularly interferons. Once activated, the immune system can efficiently battle the unwelcome intruders. In a way, Larifan mimics a viral infection and prepares our immune system for a virus attack so it is ready to fight once needed. Larifan has been known to alleviate multiple virus-caused symptoms, such as herpes and influenza (https://larifan.eu/en/). Thus, we wanted to test its activity against the newly emerged SARS-CoV-2. To archive this, we set up two types of models – one in vitro (meaning usage of human cells in a culture dish) and the other in vivo (involving laboratory animals) (Fig. 1) [1]. To begin with, we set up an experiment to test Larifans’ effect on cells SARS-CoV-2 would infect in a human, such as lung tissue (human lung adenocarcinoma cell line (Calu3)) or airway epithelium (primary human small airway epithelial cells (HSAEC)). The cells were cultured in a Petri dish, and Larifan was added either before the SARS-CoV-2 infection, or after, or kept within the culture throughout the length of the experiment. We then measured the amount of virus particles present, and found that the addition of Larifan reduced the amount of SARS-CoV-2 (example visualised in Fig. 2).