Controversies’ clarification regarding ribavirin efficacy in measles and coronaviruses: Comprehensive therapeutic approach strictly tailored to COVID-19 disease stages

Table 1 Ribavirin’s antiviral activity and clinical uses

Type of virus	Antiviral activities and clinical uses
DNA viruses	HSV1, 2[8]; CMV at higher concentrations[9]; Several adenovirus serotypes[10]
RNA viruses	HCV non-genotype 1: RBV + PEG-IFN; although, none of the drugs seems to have direct effect on virus. RBV enhances the pSTAT4 and IFN-γ response of NK cells to IFN-α stimulation[11]; however, in later studies, RBV was found to induce significantly more G-to-A and C-to-U transitions, a genetic signature that is indicative of RBV-induced mutagenesis[12,13]. HEV: In transplant recipients treated for HEV, RBV ensures a sustained virological response[14]. Pre-treatment HEV polymerase mutations and de novo mutations under ribavirin did not have a negative impact on HEV clearance[15]. RSV: RBV is a well-tolerated option to treat RSV infections in immunocompromised patients[16,17]. β-Coronaviruses, comprising MHV-3, SARS-CoV, MERS-CoV, and SARS-CoV-2 (see text for extensive data). Influenza virus (A and B)[18]; Paramyxoviruses[19]; Measles (see text); Mumps[20]; Parainfluenza types 1, 2, 3[21]; Rhinoviruses exhibit variable sensitivity[22], while combination treatment was effective in patients with hypogammaglobinemia[23]. HIV (in vitro)[24], WNV (flavivirus): RBV lowers RNA levels and reduces cytopathogenicity in vitro[25]. Poliovirus and coxsackie B virus are insensitive[9], Hemorrhagic fever viruses, including arenaviruses, bunyaviruses, hantaviruses, filoviridae (Marburg and Ebola viruses) and the Flaviviridae (yellow fever and dengue virus). RBV is effective against most of these major pathogens, except for Ebola, Marburg, yellow fever, dengue, and Machupo virus[26]. Arenaviruses: LCMV inhibition is also mediated through a decrease in GTP levels[27]. Crimean-Congo hemorrhagic fever: RBV is the only antiviral treatment with decreased fatality rates[28,29]. Lassa fever and Hantaan virus have been tested and showed potential susceptibility in vitro and/or in animal models[30,31]

DNA: Deoxyribonucleic acid; RNA: Ribonucleic Acid; CMV: Cytomegalovirus; GTP: Guanosine triphosphate; HCV: Hepatitis C virus; HEV: Hepatitis E virus; HIV: Human immunodeficiency virus; HSV1,2: Herpes simplex virus 1 and 2; IFN: Interferon; LCMV: Lymphocytic choriomeningitis virus; MERS-CoV: Middle East respiratory syndrome; MHV-3: Mouse hepatitis virus strain-3; NK: Natural killer; PEG-IFN: Pegylated-interferon; RBV: Ribavirin; RSV: respiratory syncytial virus; SARS-CoV: Severe acute respiratory syndrome; SARS-CoV-2: Severe acute respiratory syndrome-2; WNV: West Nile virus.