Naproxen Exhibits Broad Anti-influenza Virus Activity in Mice by Impeding Viral Nucleoprotein Nuclear Export

Zheng, Wei; Fan, Wenhui; Zhang, Shuang; Jiao, Peng; Shang, Yue; Cui, Liang; Mahesutihan, Madina; Li, Jing; Wang, Dayang; Gao, George F.; Sun, Lei; Liu, Wenjun

doi:10.1016/j.celrep.2019.04.053

Cited by 59 publications

(49 citation statements)

References 42 publications

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“…These values are consistent with the determination of the free energies of naproxen binding to N. We cannot exclude additional putative naproxen binding sites of naproxen in the C-terminal domain of SARS-CoV2 or in the unstructured serine-rich domain that could enable naproxen to further interfere with N functions. In addition to the antiviral activity against SARS-CoV-2 virus demonstrated here, naproxen also exhibited antiviral properties in cellular and rodent models of Influenza A and B 6,10,26 . Naproxen also inhibited the replication of the unrelated Zika virus 27 .…”

Section: Naproxen Inhibits Sars-cov-2 Infection In Veroe6 Cells and Imentioning

confidence: 63%

Broad-spectrum antiviral activity of naproxen: from Influenza A to SARS-CoV-2 Coronavirus

Terrier

Dilly

Pizzorno

et al. 2020

Preprint

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There is an urgent need for specific antiviral drugs directed against SARS-CoV-2 both to prevent the most severe forms of COVID-19 and to reduce viral excretion and subsequent virus dissemination; in the present pandemic context, drug repurposing is a priority. Targeting the nucleoprotein N of the SARS-CoV-2 coronavirus in order to inhibit its association with viral RNA could be a strategy to impeding viral replication and possibly other essential functions associated with viral N. The antiviral properties of naproxen, belonging to the NSAID family, previously demonstrated against Influenza A virus, were evaluated against SARS-CoV-2. Naproxen binding to the nucleoprotein of SARS-CoV2 was shown by molecular modeling. In VeroE6 cells and reconstituted human primary respiratory epithelium models of SARS-CoV-2 infection, naproxen inhibited viral replication and protected the bronchial epithelia against SARS-CoV-2 induceddamage. The benefit of naproxen addition to the standard of care is tested in an on-going clinical study.

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Section: Naproxen Inhibits Sars-cov-2 Infection In Veroe6 Cells and Imentioning

confidence: 63%

Broad-spectrum antiviral activity of naproxen: from Influenza A to SARS-CoV-2 Coronavirus

Terrier

Dilly

Pizzorno

et al. 2020

Preprint

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“…Some of the compounds in this family have anti-viral properties in addition to anti-inflammatory properties, which makes them appropriate for treating viral respiratory infections. 8,9 Although these medications have been used in respiratory infections for years, there is still no definitive conclusion regarding which compound is most effective and safe.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, there are pre-clinical evidence that indicate the antiviral properties of naproxen. For instance, Zheng et al showed that naproxen shows wide-spectrum antiviral effects in mice with influenza 8. Naproxen inhibits nucleoprotein binding to RNA and consequently inhibits replication in viruses 35.…”

mentioning

confidence: 99%

Non‐steroidal anti‐inflammatory drugs in management of COVID‐19; A systematic review on current evidence

et al. 2020

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Background Since there is still no definitive conclusion regarding which non‐steroidal anti‐inflammatory drugs (NSAIDs) are most effective and safe in viral respiratory infections, we decided to evaluate the efficacy and safety of various NSAIDs in viral respiratory infections so that we can reach a conclusion on which NSAID is best choice for coronavirus disease 2019 (COVID‐19). Methods A search was performed in Medline (via PubMed), Embase and CENTRAL databases until 23 March 2020. Clinical trials on application of NSAIDs in viral respiratory infections were included. Results Six clinical trials were included. No clinical trial has been performed on COVID‐19, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome infections. Studies show that ibuprofen and naproxen not only have positive effects in controlling cold symptoms, but also do not cause serious side effects in rhinovirus infections. In addition, it was found that clarithromycin, naproxen and oseltamivir combination leads to decrease in mortality rate and duration of hospitalisation in patients with pneumonia caused by influenza. Conclusion Although based on existing evidence, NSAIDs have been effective in treating respiratory infections caused by influenza and rhinovirus, since there is no clinical trial on COVID‐19 and case‐reports and clinical experiences are indicative of elongation of treatment duration and exacerbation of the clinical course of patients with COVID‐19, it is recommended to use substitutes such as acetaminophen for controlling fever and inflammation and be cautious about using NSAIDs in management of COVID‐19 patients until there are enough evidence. Naproxen may be a good choice for future clinical trials.

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“…SARS-CoV-2 was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China, at the end of 2019 3 Since the first reports of cases from China, the number of infected diseases has been rising daily in this country and other countries 4 . The origin of SARS-CoV-2 was in enzootic bat viruses and then transmitted from presymptomatic or asymptomatic infected cases 5 . SARS-CoV-2 is closely related to SARS-CoV containing a 30kb genome organized into several ORFs necessary for viral infection and replication in the host cells.…”

Section: Introductionmentioning

confidence: 99%

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

Lagzian

Valadan

Saeedi

et al. 2020

Preprint

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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.

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Naproxen Exhibits Broad Anti-influenza Virus Activity in Mice by Impeding Viral Nucleoprotein Nuclear Export

Cited by 59 publications

References 42 publications

Broad-spectrum antiviral activity of naproxen: from Influenza A to SARS-CoV-2 Coronavirus

Broad-spectrum antiviral activity of naproxen: from Influenza A to SARS-CoV-2 Coronavirus

Non‐steroidal anti‐inflammatory drugs in management of COVID‐19; A systematic review on current evidence

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

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