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.
Bibliographical noteFunding Information:
This study was funded by Netherlands Organisation for Scientific Research (VIDI grant: No. 91719300), and China Scholarship Council for PhD fellowships (Nos. 201903250082, 201808370170, 201708620177, 201708530243, 201703250073).
This study is supported by a VIDI Grant (No. 91719300) from the Netherlands Organisation for Scientific Research (NWO) to Q. Pan, and the China Scholarship Council for funding PhD fellowships to Yining Wang (No. 201903250082), Pengfei Li (No. 201808370170), Peifa Yu (No. 201708620177), Yunlong Li (No. 201708530243), and Yang Li (No. 201703250073). The authors thank Dr. Lia van der Hoek (Amsterdam UMC location AMC, University of Amsterdam, the Netherlands) for providing the stock of human coronavirus NL63. The authors also thank Dr. Bart Haagmans (Department of Viroscience, Erasmus MC) for providing the stock of SARS-CoV-2.
© 2021, The Author(s).