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

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.

Evaluation of Receptor Relationships of Some Drugs Used in the Treatment of COVID-19 by Modeling Studies

“…20 In another study, Wang et al investigated the binding affinities of the favipiravir to SARS-CoV-2 and human coronavirus NL63 RNA-dependent RNA polymerase (RdRp) and indicated that favipiravir has similar binding affinities to these proteins. 22 In the present study, we show for the first time the interactions of these drugs with the ER, PR and HER2 receptors and evaluate their binding affinities. Thus, it will help to understand how ER, PR, and HER2 receptor pathways can be affected in cellular mechanisms in vitro when these drugs are used by normal individuals and breast cancer patients who have COVID-19.…”

“…Molecular docking studies using either of these drugs in previous studies in the literature have generally investigated the binding of drugs to a SARS-CoV-2 protein. 18,[20][21][22] Celik et al analyzed the interactions of both hydroxychloroquine and chloroquine with proteins of SARS-CoV-2 such as SARS-CoV-2 RNA polymerase, main protease and spike proteins which play an important role in the structure, survival, reproduction, attachment and survival of the SARS-CoV-2 virus. 20 They showed that neither hydroxychloroquine nor chloroquine do not act on SARS-CoV-2 proteins however both molecules prevent the binding of SARS CoV-2 spike protein to angiotensin-converting enzyme 2 (ACE2) by inter-acting with the allosteric site.…”

Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants

“…In vitro remdesivir shows a broad spectrum of antiviral activity against RNA viruses by targeting replicase such as RdRp [52,72]. Remdesivir can also inhibit the SARS-CoV-2 RdRp [51,53,[73][74][75]. Remdesivir can also dock the 3CLpro replicase [49,51,76,77].…”

Repurposing of potential antiviral drugs against RNA-dependent RNA polymerase of SARS-CoV-2 by computational approach

“…As the experimental validations were found to be partially successful, they have been approved for restricted use only for treating COVID-19 patients belonging to specific groups [32] , [33] , [34] . Similarly, several in silico molecular modelling and preclinical studies have also suggested the plausibility of the above mentioned antiviral compounds to control and prevent the replication and transcription of SARS-CoV-2 [35] . However, those studies have reported different compounds as the top ranked compounds against RdRp [21] , [36] , [37] , [38] .…”