Study of Riamilovir Activity Against SARS-CoV-2 Infection In Syrian Hamsters

Abstract

The activity of the antimetabolic drug Riamilovir (Triazavirin®) was studied on a model of SARS-CoV-2 infection on Syrian hamsters. Infectious process was caused by the intranasal administration of the virus accumulated in the Vero-B culture with a concentration of 4.25×104 TCID50, in a volume of 26 µl/hamster. The effects of the drug at a dose of 20 mg/kg intraperitoneally daily in the midst of the infectious process were traced to accelerate the clearance of the virus in the lungs, prevent body weight loss and the severity of pulmonary edema, as well as preserve the mass of the spleen. The protective effects of Riamilovir on the structure of the lungs and brain are shown, it is suggested that the drug has the ability to penetrate the blood-brain barrier. It was concluded that Riamilovir has antiviral activity against SARS-CoV-2.

Triazavirin—A Novel Effective Antiviral Drug

“…Moreover, its alkylated derivatives and salts with other alkali metals and ammonium cations also demonstrate significant or good antiviral activity against influenza, West Nile fever, Rift Valley fever, the Dengue, and Venezuelan encephalitis. The efficacy of Triazavirin against SARS-CoV-2 has been demonstrated in preclinical [ 76 ] and several clinical trials [ 20 , 21 , 22 , 23 , 24 , 25 ], including a multicenter, randomized, placebo controlled, double-blind trial [ 27 ]. Nowadays, according to some other studies [ 19 , 68 , 69 ] performed, Riamilovir is included in the guideline for ARVI treatment by the Ministry of Health of Russian Federation for use in etiotropic therapy against ARVI [ 86 ].…”

“…Data on Riamilovir (Triazavirin) effects on SARS-CoV-2 replication in lungs and dynamics of pathomorphological changes in internal tissues of Syrian hamsters have recently been published [ 76 ]. Animals in the studied group received the drug intraperitoneally every day at a dose of 20 mg/kg from day 3 to 7 after infection, while the positive control group received injections of saline in an equivalent volume, and intact animals were used as negative controls ( Figure 2 ).…”

“…The data obtained revealed that the rate of virus elimination from lung tissue was enhanced nearly 2-fold, while elimination half-life was shortened by approximately 1 day on treatment with Riamilovir (Triazavirin). Therefore, it was concluded that Triazavirin exhibits antiviral activity against SARS-CoV-2 virus in in vivo experiments [ 76 ].…”

Development of Drugs with Direct Antiviral Action Based on Azaheterocyclic Systems

“…The good safety profile of riamilovir (triazavirin) with no side effects made it possible to recommend this drug as the first stage of outpatient therapy for patients with COVID-19, based on the principle of multiple exposures [ 21 ]. Also note that experimental data on the effectiveness of triazavirin in experiments on Syrian hamsters infected with the SARS-CoV-2 virus were obtained at the State Research and Testing Institute of Military Medicine (St. Petersburg) [ 24 ]. The efficacy and safety of triazavirin was also evaluated in clinical institutions in Harbin [ 25 ].…”