Bacteriophage-Derived Double-Stranded RNA Exerts Anti-SARS-CoV-2 Activity In Vitro and in Golden Syrian Hamsters In Vivo

Abstract

Bacteriophage-derived dsRNA, known as Larifan, is a nationally well-known broad-spectrum antiviral medication. This study aimed to ascertain the antiviral activity of Larifan against the novel SARS-CoV-2 virus. Larifan’s effect against SARS-CoV-2 in vitro was measured in human lung adenocarcinoma (Calu3) and primary human small airway epithelial cells (HSAEC), and in vivo in the SARS-CoV-2 infection model in golden Syrian hamsters. Larifan inhibited SARS-CoV-2 replication both in vitro and in vivo. Viral RNA copy numbers and titer of infectious virus in the supernatant of Calu3 cells dropped significantly: p = 0.0296 and p = 0.0286, respectively. A reduction in viral RNA copy number was also observed in HSAEC, especially when Larifan was added before infection (p = 0.0218). Larifan markedly reduced virus numbers in infected hamsters’ lungs post-infection, with a more pronounced effect after intranasal administration (p = 0.0032). The administration of Larifan also reduced the amount of infections virus titer in the lungs (p = 0.0039). Improvements in the infection-induced pathological lesion severity in the lungs of animals treated with Larifan were also demonstrated. The inhibition of SARS-CoV-2 replication in vitro and the reduction in the viral load in the lungs of infected hamsters treated with Larifan alongside the improved lung histopathology suggests a potential use of Larifan in also controlling the COVID-19 disease in humans.

Loss of Recurrent Laryngeal Papillomatosis following Postsurgical Treatment with dsRNA Interferon Inducer

“…dsRNA is a well-known and potent interferon inducer, and studies have demonstrated the wide-reaching effects Larifan exerts on immune cells beyond interferon [ 18 ]. Studies have explored this drug as an antiviral and antitumor treatment option with promising results in cervical cancer, recurrent herpes simplex infection, chlamydia trachomatis infection models, and most recently, even SARS-CoV-2 [ 14 , 19 – 21 ].…”

“…No. 04-0230); however, it was shown that it could also be effective in the treatment of other infections, such as SARS-CoV-2 and papillomaviruses [ 14 , 15 ]. After the course of the prescribed therapy, the symptoms no longer appeared.…”

“…It contains bacteriophage-derived dsRNA and is a potent inducer of endogenous type I interferons (IFNs) and acts as a polyfunctional and wide-spectrum antiviral drug [ 11 ]. It has been shown to induce and activate several enzymes of the IFN system involved in the blockade of translation of infected cells [ 12 – 14 ]. Furthermore, it is an affordable and over-the-counter medication.…”