Abstract
Human coronavirus NL63 (HCoV-NL63) mainly affects young children and immunocompromised patients, causing morbidity and mortality in a subset of patients. Since no specific treatment is available, this study aims to explore the anti-SARS-CoV-2 agents including favipiravir and remdesivir for treating HCoV-NL63 infection. We first successfully modelled the 3D structure of HCoV-NL63 RNA-dependent RNA polymerase (RdRp) based on the experimentally solved SARS-CoV-2 RdRp structure. Molecular docking indicated that favipiravir has similar binding affinities to SARS-CoV-2 and HCoV-NL63 RdRp with LibDock scores of 75 and 74, respectively. The LibDock scores of remdesivir to SARS-CoV-2 and HCoV-NL63 were 135 and 151, suggesting that remdesivir may have a higher affinity to HCoV-NL63 compared to SARS-CoV-2 RdRp. In cell culture models infected with HCoV-NL63, both favipiravir and remdesivir significantly inhibited viral replication and production of infectious viruses. Overall, remdesivir compared to favipiravir is more potent in inhibiting HCoV-NL63 in cell culture. Importantly, there is no evidence of resistance development upon long-term exposure to remdesivir. Furthermore, combining favipiravir or remdesivir with the clinically used antiviral cytokine interferon-alpha resulted in synergistic effects. These findings provided a proof-of-concept that anti-SARS-CoV-2 drugs, in particular remdesivir, have the potential to be repurposed for treating HCoV-NL63 infection.
Highlights
Human coronavirus NL63 (HCoV-NL63) mainly affects young children and immunocompromised patients, causing morbidity and mortality in a subset of patients
Remdesivir has become the first FDA-approved antiviral drug for treating hospitalized COVID-19 p atients[16]. Both favipiravir and remdesivir act on RNA-dependent RNA polymerase (RdRp) to inhibit viral replication
The homology-based 3D structure of HCoV-NL63 RdRp was modelled in MODELLER 9.2421 based on the SARS-CoV-2 RdRp electron microscopic structure with a resolution of 2.93 Å
Summary
Human coronavirus NL63 (HCoV-NL63) mainly affects young children and immunocompromised patients, causing morbidity and mortality in a subset of patients. Since no specific treatment is available, this study aims to explore the anti-SARS-CoV-2 agents including favipiravir and remdesivir for treating HCoV-NL63 infection. Combining favipiravir or remdesivir with the clinically used antiviral cytokine interferonalpha resulted in synergistic effects These findings provided a proof-of-concept that anti-SARS-CoV-2 drugs, in particular remdesivir, have the potential to be repurposed for treating HCoV-NL63 infection. Remdesivir has become the first FDA-approved antiviral drug for treating hospitalized COVID-19 p atients[16] Both favipiravir and remdesivir act on RNA-dependent RNA polymerase (RdRp) to inhibit viral replication. We first comparatively assessed the binding affinities of favipiravir or remdesivir to SARS-CoV-2 and HCoV-NL63 RdRp by molecular docking We investigated their antiviral activities in cell culture models infected with HCoV-NL63, as well as the combinatory effects with the clinically used antiviral cytokine interferon-alpha (IFN-α)
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