tetano
Editor, Senior Moderator
Sci Rep
. 2021 Dec 6;11(1):23465.
doi: 10.1038/s41598-021-02972-y.
Comparative assessment of favipiravir and remdesivir against human coronavirus NL63 in molecular docking and cell culture models
Yining Wang[SUP] 1 [/SUP], Pengfei Li[SUP] 1 [/SUP], Sajjan Rajpoot[SUP] 2 [/SUP], Uzma Saqib[SUP] 3 [/SUP], Peifa Yu[SUP] 1 [/SUP], Yunlong Li[SUP] 1 [/SUP], Yang Li[SUP] 1 [/SUP], Zhongren Ma[SUP] 4 [/SUP], Mirza S Baig[SUP] #[/SUP][SUP] 5 [/SUP], Qiuwei Pan[SUP] #[/SUP][SUP] 6 [/SUP]
Affiliations
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.
. 2021 Dec 6;11(1):23465.
doi: 10.1038/s41598-021-02972-y.
Comparative assessment of favipiravir and remdesivir against human coronavirus NL63 in molecular docking and cell culture models
Yining Wang[SUP] 1 [/SUP], Pengfei Li[SUP] 1 [/SUP], Sajjan Rajpoot[SUP] 2 [/SUP], Uzma Saqib[SUP] 3 [/SUP], Peifa Yu[SUP] 1 [/SUP], Yunlong Li[SUP] 1 [/SUP], Yang Li[SUP] 1 [/SUP], Zhongren Ma[SUP] 4 [/SUP], Mirza S Baig[SUP] #[/SUP][SUP] 5 [/SUP], Qiuwei Pan[SUP] #[/SUP][SUP] 6 [/SUP]
Affiliations
- 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.