Repurposing naproxen as a potential antiviral agent against SARS-CoV-2

Abstract

The Outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in late 2019 in China and many other countries around the world necessitate immediate action to develop new drugs against the virus. Repurposing of existing drugs for new targets is a fast, safe and unexpansive approach for this goal. Studies have shown that naproxen could specifically interact with the RNA binding domain of nueclporteins of RNA viruses such as the influenza virus. Therefore, this study aimed to evaluate the binding properties of naproxen to the nucleocapsid protein of SARS-CoV-2. 3D structure of N and C terminal domains of SARS-CoV- 2 nucleocapsid were constructed and each were docked with naproxen and analyzed during 100 ns of molecular dynamics. The results showed that naproxen interacts with the N terminal domain of the nucleocapsid via two salt bridges with Arg 88 and 92 and a network of h-bonds. Molecular dynamics analysis was also revealed that all the coordinations of naproxen with N terminal domain were kept during 100 ns of simulation time. The results of this study provide insights how naproxen can specifically interact with the conserved RNA binding module of the nucleocapsid of SARS-CoV-2 that would inhibit the packaging of viral genome into capsid and virus assembly. Therefore we recommend evaluating the antiviral effects of naproxen against SARS-CoV-2 in in vitro studies and clinical trials.

Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study

“…This is reflected by the fact that these three compounds were favorably sampled at the interface after the reclassified run in each case as the most thermodynamically feasible, but under the sampling conditions of this study (see Table 1 and Figure 1). Although this is the first study that considers the docking of this type of compound at the level of the RBD-ACE2 interface, our results coincide with those obtained by other authors who have found that Ibuprofen can have a docking score considerably better than other NSAIDs compared to proteins associated with SARS-CoV-2 [44], and that some derivatives could effectively interact with protein regions involved in this complex [76]. These NSAIDs drugs exhibited very close Ki.…”

“…The WHO has indicated that there is no evidence to confirm an aggravation of COVID-19 infection with the administration of NSAIDs [30,31]. In fact, it has been reported that some NSAIDs could have some type of activity against viruses such as VZV [32], HCMV [32], HSV-1 [33], influenza virus A⁄ H1N1 subtype [34,35], VSV [36,37], EBOLA [38,39], HIV [40], JEV [41], CHIKV [42], SARS-CoV-1 [43], and recently against SARS-CoV-2 [35,44,45]. Additionally, many studies have been carried out that propose various targets for blocking virus recognition, importation and replication processes through the use of reused drugs, immunotherapies, interference strategies and various inhibitory compounds [46].…”

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19

“…Hot spot residues are the fraction of PPI residues that account significantly for the overall protein–protein binding affinity, and they are typically determined experimentally using alanine scanning mutagenesis In the N-terminal domain of nucleocapsid protein tetramer (PDB: 6VYO), three critical RNA-binding residues on the beta-sheet core were included in docking: Arg88, Arg92, and Arg107 , …”

“…In the N-terminal domain of nucleocapsid protein tetramer (PDB: 6VYO), three critical RNA-binding residues on the beta-sheet core were included in docking: Arg88, Arg92, and Arg107 , …”