Researchers have identified an RNA molecule that stimulates the body’s early antiviral defence system, and can protect mice from a range of variants of SARS-CoV-2, the virus that causes Covid-19. The study, published on Wednesday in the Journal of Experimental Medicine, could lead to new treatments for Covid-19 in immunocompromised patients, and provide an inexpensive therapy for developing countries that currently lack access to vaccines.
The body’s first line of defence against SARS-CoV-2 — before the involvement of antibodies and T cells — is thought to depend on receptor molecules such as RIG-I that recognise the virus’s genetic material and induce the production of signalling proteins known as type I interferons. The researchers at Yale School of Medicine in the US noted that these interferons promote the production of proteins that can inhibit viral reproduction and stimulate the recruitment of immune cells to fight the infection.
Multiple studies have suggested that early and robust production of interferons protects against Covid-19, whereas delayed production is associated with severe disease, they said. The researchers noted that treating patients with short RNA molecules that mimic SARS-CoV-2’s genetic material and activate the RIG-I receptor to stimulate production of type I interferons by the body’s own cells can reduce mortality.
Ribonucleic acid (RNA) is a molecule essential in various biological roles in coding, decoding, regulation and expression of genes. The team tested its approach in mice susceptible to SARS-CoV-2 infection.
A single dose of an RNA molecule named SLR14 was sufficient to protect the mice from severe disease and death, particularly if the treatment was provided shortly before or soon after exposure to the virus, the researchers said. SLR14 protected mice from all SARS-CoV-2 variants, including Delta, they said.
The researchers also tested SLR14 in immunocompromised mice chronically infected with SARS-CoV-2. The RNA molecule was able to completely clear the virus from these animals, even though they lack both T cells and antibody-producing B cells, they said.
The team noted that RNA molecules like SLR14 are relatively cheap and easy to manufacture. “SLR14 therefore holds great promise as a new class of RNA therapeutics that can be applied as antivirals against SARS-CoV-2," said Akiko Iwasaki, a professor at Yale School of Medicine.
“Moreover, because this RNA-based therapeutic approach is simple and versatile, our study will facilitate pandemic preparedness and response against future respiratory pathogens sensitive to type I interferons," Iwasaki said. Although approved Covid-19 vaccines are highly effective at preventing severe disease and death, vaccine availability is extremely limited in many low-income countries.
The researchers said the effectiveness of vaccines is already reduced in immunocompromised individuals unable to form sufficient numbers of antibodies or T cells that specifically target the viral spike protein. These individuals are susceptible to chronic, long-term SARS-CoV-2 infections, they explained.
“This is why, in addition to the use of vaccines in preventing Covid-19, efforts are required to develop efficacious therapeutics against SARS-CoV-2, Iwasaki added.