RIG-I-induced innate antiviral immunity protects mice from lethal SARS-CoV-2 infection

Abstract

The SARS-CoV-2 pandemic has underscored the need for rapidly employable prophylactic and antiviral treatments against emerging viruses. Nucleic acid agonists of the innate immune system can be administered to activate an effective antiviral program for prophylaxis in exposed populations, a measure of particular relevance for SARS-CoV-2 infection due to its efficient evasion of the host antiviral response. In this study, we utilized the K18-hACE2 mouse model of COVID-19 to examine whether prophylactic activation of the antiviral receptor RIG-I protects mice from SARS-CoV-2 infection. Systemic treatment of mice with a specific RIG-I ligand one to seven days prior to infection with a lethal dose of SARS-CoV-2 improved their survival of by up to 50 %. Improved survival was associated with lower viral load in oropharyngeal swabs and in the lungs and brain of RIG-I-treated mice. Moreover, despite antiviral protection, the surviving mice that were treated with RIG-I ligand developed adaptive SARS-CoV-2-specific immunity. These results reveal that prophylactic RIG-I activation by synthetic RNA oligonucleotides is a promising strategy to convey short-term, unspecific antiviral protection against SARS-CoV-2 infection and may be a suitable broad-spectrum approach to constraining the spread of newly emerging viruses until virus-specific therapies and vaccines become available.

RIG-I and MDA5 Protect Mice From Pichinde Virus Infection by Controlling Viral Replication and Regulating Immune Responses to the Infection

“…It was noted that RIG-I SKO mice infected with the influenza virus PR8 had significantly longer viral clearance times and lower numbers of activated T cells than the infected WT mice (58). Finally, it was found that mice treated with RIG-I-activating ligand prior to infection by SARS-CoV-2 had increased survivability, decreased viral titers and increased antibody responses as compared to the virus-infected WT mice, as described in a recent preprint (59). Taken together, these findings indicate that RIG-I and MDA5 consistently provide antiviral protection in mice by inducing early IFN-I expression to inhibit virus replication, as shown in our current study (Figures 2, 3).…”

Non-coding RNAs derived from the foot-and-mouth disease virus genome trigger broad antiviral activity against coronaviruses

“…Direct comparison of the in vivo anticoronavirus activity of poly(I:C) and the FMDV ncRNAs will be of interest for future work. Several agonists of viral immune sensors RIG-I and STING have yielded better results than recombinant IFN in K18-hACE2 mice likely due to reduced production of anti-type I IFN autoantibodies and broader stimulation of antiviral effectors (45)(46)(47)(48). Prophylactic treatment with a 14-bp RNA duplex at 16 or 2 h before infection protected mice from clinical disease after SARS-CoV-2 infection (45).…”

“…Prophylactic treatment with a 14-bp RNA duplex at 16 or 2 h before infection protected mice from clinical disease after SARS-CoV-2 infection (45). Similarly, administration of a synthetic 5´-triphosphate dsRNA RIG-I ligand 1 day before SARS-CoV-2 infection increased the survival rate and reduced viral burden after challenge (46). In both cases, the RNAs were injected intravenously and complexed with a polyethylenimine-based transfection reagent.…”

A clinical-statistical study on COVID-19 infection and death status at the Alshifaa Healthcare Center/ Baghdad

“…3 Unfortunately, not all countries succeeded in these attempts; in fact, the overall situation shows that these regulations were not enough and the virus continues spreading. 4 After one year of its detection, SARS-CoV-19 had a modification when genetic mutations occurred and resulted in a new type of it named novel coronavirus. This was not the only change in the virus structure, where a continuous modification is occurring and new versions of the virus are mutating.…”

“…2 Different protocols of therapy were used to treat COVID-19 patients; these included different types of medications, practices, types of food and herbs, etc. 3,4 As a result, the mortality rate decreased gradually comparing with the first period of the disease spreading. These treatment methods were accompanied with developing many vaccines from different countries and companies, where a tough competition was undertaken to come up with a solution for this pandemic.…”