Development of small interfering RNAs (siRNAs) for the treatment of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) [Added supplement: COVID-19 Variant Supplement]

SARS-CoV-2 is responsible for the current coronavirus disease 2019 (COVID-19) pandemic for which there are no treatments yet available. We propose to rapidly design and test several drugs that could be delivered intranasally to treat SARS-CoV-2. We will also analyze the immune response to the virus in patient cells to determine a possible correlation between the early response and the outcome of the disease. The technology we will use is called RNA interference and it works by using what are called small interfering RNAs (siRNAs). siRNAs can direct a person's existing RNA interference machinery to attack any harmful RNA sequence such as the RNA genome of SARS-CoV-2. Furthermore, by reducing the viral burden, siRNAs could contribute to mounting a patient's natural immune response to the virus. We will also design siRNAs to target any factor that would prevent the immune response in the early phase of the disease. siRNAs are easy to design, manufacture and are stable for long-term storage and transport. An advantage for their use as therapy for respiratory infections is that they remain in the lungs when administered intranasally and therefore have low potential to cause side-effects in other parts of the body. We expect that from our project we will identify a safe and effective treatment that could be used in the fight against the current pandemic and future outbreaks of related coronaviruses.