Repurposed nystatin to inhibit SARS-CoV-2 and mutants in the GI tract

Abstract

AbstractThe SARS-CoV-2 infections are considered as respiratory system diseases, mostly. In COVID-19, it might also be the infection of gastrointestinal (GI) tract too, especially at patients in severe clinical condition. SARS-CoV-2 can destroy the intestinal barrier, capable to spread into internal organs via blood and/or lymphatic circulation, and to cause serious damage there. Infected GI tract of COVID-19 patients is ideal environment for the coronavirus infection, replication and as virus reservoir might be the major source of pandemic reinfections, too. The process of virus budding is dependent on the host cell lipid rafts containing membrane-sterols, mainly cholesterol. The viral envelope may be challenged by polyene antibiotics, such as nystatin, which has strong affinity to sterols. Nystatin may block the establishment of the virus-host cell connection, too. In this study, the nystatin was investigated, as antiviral agent to SARS-CoV-2. We demonstrated by tests in Vero E6 cell based cytopathic assay, nystatin blocked the replication of SARS-CoV-2 in concentration 62.5 μg/ml (IC50) at Wuhan and British mutant strains. No efficient SARS-CoV-2 antiviral agent is known so far to alleviate pandemic, to disinfect GI tract, where vaccines might have limited effect, only. Nystatin might be the first one with emergency use authorization, either, as a safe and efficient non-systemic antiviral drug, with well-established use, since decades.