Comparative assessment of favipiravir and remdesivir against human coronavirus NL63 in molecular docking and cell culture models

  • Sci Rep. 2021 Dec 6;11(1):23465. doi: 10.1038/s41598-021-02972-y.
Yining Wang  1 ,  Pengfei Li  1 ,  Sajjan Rajpoot  2 ,  Uzma Saqib  3 ,  Peifa Yu  1 ,  Yunlong Li  1 ,  Yang Li  1 ,  Zhongren Ma  4 ,  Mirza S Baig   #  5 ,  Qiuwei Pan   #  6
Affiliations
  • 1. Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Room Na-1005, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
  • 2. Department of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Simrol, Indore, 453552, MP, India.
  • 3. Department of Chemistry, Indian Institute of Technology Indore (IITI), Simrol, Indore, 453552, MP, India.
  • 4. Biomedical Research Center, Northwest Minzu University, Lanzhou, China.
  • 5. Department of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Simrol, Indore, 453552, MP, India. [email protected].
  • 6. Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Room Na-1005, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands. [email protected].
  • # Contributed equally.
PMID: 34873274 DOI: 10.1038/s41598-021-02972-y
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.

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