Science & Technology

Researchers at Yale University are developing RNA-based therapies that can protect against a variety of COVID-19 mutants

Treatment with SLR14 (right) compared to the control (left) reduces lung inflammation and signs of pneumonia in SARS-CoV-2 infected mice. Credits: © 2021 Mao et al.Originally released Experimental Medicine Journal..

Researchers at Yale School of Medicine RNA Molecules that stimulate the body’s early antiviral defense system can protect mice from various emergences SARS-CoV-2 variant.Recently published research Experimental Medicine Journal ((((JEM), May lead to new treatments for COVID-19 (new coronavirus infection) It provides cheap treatment options for immunocompromised patients and for developing countries who currently lack access to vaccines.

Approved vaccines for SARS-CoV-2 are very effective in preventing serious illness and death during an ongoing COVID-19 pandemic, but vaccine availability is available in many low-income countries. Very limited and new vaccine resistant strains of the virus may emerge in the future. In addition, the effectiveness of the vaccine is already diminished in immunocompromised individuals who are unable to form sufficient numbers of antibodies or T cells that specifically target the viral peplomer. These individuals are vulnerable to chronic long-term SARS-CoV-2 infections.

“This is why, in addition to using vaccines to prevent COVID-19, efforts are needed to develop effective treatments for SARS-CoV-2,” said Akiko Iwasaki, a professor at Yale School of Medicine. increase.

The body’s first line of defense against SARS-CoV-2 prior to the involvement of antibodies and T cells is a receptor such as RIG-I that recognizes the viral genetic material and induces the production of signaling proteins known as types. It is believed to be molecule dependent. I will interfere. These interferons, in turn, stimulate the production of proteins that can inhibit viral replication and stimulate the recruitment of immune cells to fight infection.

Studies suggest that early and potent production of interferon is protected from COVID-19, whereas delayed production is associated with serious disease. Clinical trials have shown that treating COVID-19 patients with purified interferon protein early in the disease can reduce mortality, but interferon production is very expensive.

New JEM Studies show that Iwasaki et al. Propose cheaper alternatives. Patients are treated with a short RNA molecule that mimics the genetic material of SARS-CoV-2 and activates the RIG-I receptor to stimulate the production of type I interferon by the body’s own cells.

Researchers tested the approach in mice susceptible to SARS-CoV-2 infection. A single dose of an RNA molecule named SLR14 was sufficient to protect mice from severe illness and death, especially if treatment was provided immediately before or after exposure to the virus. When administered immediately after viral infection, the researchers determined that SLR14 was more effective than treating mice with purified interferon protein.

Importantly, SLR14 protected mice from all new SARS-CoV-2 variants, including the delta variant that caused the recent surge in US COVID-19 cases.

Finally, Iwasaki et al. Tested SLR14 in an immunocompromised state. Rug– –/ /– – Mice chronically infected with SARS-CoV-2. The RNA molecule was able to completely eliminate the virus from these animals, despite the lack of both T cells and antibody-producing B cells.

Iwasaki et al. Point out that RNA molecules such as SLR14 are relatively inexpensive and easy to manufacture. “Therefore, SLR14 has great promise as a new class of RNA therapeutics that can be applied as an antiviral drug against SARS-CoV-2,” says Iwasaki. “Furthermore, because this RNA-based therapeutic approach is simple and versatile, our research will facilitate pandemic preparation and response to future respiratory pathogens susceptible to type I interferon.”

Reference: “Stemloop RNA RIG-I agonists protect against acute and chronic SARS-CoV-2 infections in mice” Tianyang Mao, Benjamin Israelow, Carolina Lucas, Chantal BF Vogels, Maria Luisa Gomez-Calvo, Olga Fedorova, Mallery I. Breban, Bridget L. Menasche, Huiping Dong, Melissa Linehan, Yale SARS-CoV-2 Genome Surveillance Initiative, Craig B. Wilen, Marie L. Landry, Nathan D. Grubaugh, Anna M. Pyle, Akiko Iwasaki, November 10th 2021, Experimental Medicine Journal ((((JEM).
DOI: 10.1084 / jem.20211818

Researchers at Yale University are developing RNA-based therapies that can protect against a variety of COVID-19 mutants Researchers at Yale University are developing RNA-based therapies that can protect against a variety of COVID-19 mutants

Back to top button