## 1 Introduction  
Human parainfluenza viruses (HPIVs), single-stranded enveloped RNA viruses of the family _Paramyoxoriidae_, are responsible for common acute upper and lower respiratory infections across all age groups, with the highest infection rate in young children. HPIV infections can cause severe diseases such as group, bronchiolitis and pneumonia [1, 2]. Of the four HPIV serotypes, HPIV-3 is the most virulent, mainly causing lower respiratory tract illnesses such as bronchiolitis and pneumonia in children under 5 years old and the elderly. Infection with this virus may even be fatal in immunocompromised patients, particularly in hematopoietic stem cell transplant recipients, lung transplant recipients and children with severe combined immunodeficiency disease syndrome [3, 4, 5, 6, 7]. There are no approved antiviral drugs for the treatment of HPIV-3 infection. We therefore explored the repurposing of antiviral drugs, either alone or in combination, against infections with this virus. Several antiviral drugs have been investigated for repurposing as treatments for HPIV-3 infection, including the RNA-dependent RNA polymerase (RdRp) inhibitors remdesivir, ribavirin, and favipiravir, as well as the neuraminidase inhibitor zanamivir [8,9]. The latter drug results in a synergistic in vitro antiviral effect when combined with the entry inhibitor suramin [9].  
Ribavirin (1-9-d-ribofuranosyl-1,2,4-triazole-3-carboxamide), a guanosine analog, has broad-spectrum antiviral activity against a variety of DNA and RNA viruses [10, 11, 12]. Ribavirin has been used to treat severe infections with Lassa fever virus, hepatitis C virus (HCV), respiratory syncytial virus (RSV) and parainfluenza viruses including HPIV-3 [13,14]. A few cases have been reported where ribavirin demonstrated a therapeutic effect in clearing HPIV-3 infections [15, 16, 17]. In two small uncontrolled series involving RSV/HPIV-3 infections in recipients of allogeneic stem cell transplantation, ribavirin therapy enabled most patients to recover from the infection, with deaths occurring only in those with severe respiratory dysfunction who required mechanical ventilation [6,18]. A recent comparative analysis revealed that ribavirin therapy resulted in a significant protective effect against progression from upper to lower respiratory tract HPIV-3-induced disease as compared to untreated cohorts [19].  
Remdesivir (Veklury, Gilead Sciences), a monophosphoramidate nucleotide analog prodrug originally developed to treat HCV infections [20], has been approved for use in several countries to treat patients with COVID-19 [21]. GS-441524 is the parent nucleoside of remdesivir. Intracellularly, GS-441524 is converted to its 5\({}^{\prime}\)-triphosphate metabolite, which, as an adenosine 5\({}^{\prime}\)-triphosphate mimic, inhibits the viral RdRp [22]. Remdesivir and GS-441524 inhibit the in vitro replication of a wide range of RNA viruses such as, but not limited to RSV, parainfluenza viruses, henipaviruses and coronaviruses [23]. Antiviral activity has also been demonstrated for several of these viruses in animal infection models [24, 25, 26, 27].  
The combined use of antiviral drugs has been particularly successful in treating infections with the human immunodeficiency virus (HIV) and HCV [13, 28, 29, 30, 31]. Here, we investigated the antiviral efficacy of combined treatment of ribavirin with either remdesivir or GS-441524 against HPIV-3 infection in LLC-MK2 cells, nasal human airway epithelial cells and AG129 mice.