Viral infections in mammals can be treated and prophylactically prevented by systemic administration of ranpirnase and three other ribonucleases that are highly homologous with it and that have activities that are highly similar to it. Experimental results against rabies, Middle East Respiratory Syndrome Coronavirus (“MERS-CoV”), influenza, Ebola virus, Chikungunya virus, Venezuelan equine encephalitis, canine parvovirus, adenovirus-2, respiratory syncytial virus, rhinovirus-14, and vaccinia are disclosed.