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Drug Repurposing Approaches for the Treatment of Influenza Viral Infection: Reviving Old Drugs to Fight Against a Long-Lived Enemy
Open accessAbstract
Influenza viruses still constitute a real public health problem today. To cope with the emergence of new circulating strains, but also the emergence of resistant strains to classic antivirals, it is necessary to develop new antiviral approaches. This review summarizes the state-of-the-art of current antiviral options against influenza infection, with particular focus on the recent advances of anti-influenza drug repurposing strategies and their potential therapeutic, regulatory and economic benefits. The review will illustrate the multiple ways to reposition molecules for the treatment of influenza, from adventitious discovery to in silico-based screening. These novel antiviral molecules, many of which targeting the host cell, in combination with conventional antiviral agents targeting the virus, will ideally enter the clinics and reinforce the therapeutic arsenal to combat influenza virus infections.
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“Historically, drug combinations have been utilized efficiently to treat various bacterial and viral infections and to fight cancer [18–21].”
From Aprepitant, an antiemetic agent, interferes with metal ion homeostasis of Candida auris and displays potent synergistic interactions with azole drugs (2020) · cites this paper as [20]
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“By screening the database of small molecules against viral drug targets using computational methods, drugs or molecules can be identified may possess antiviral activity (Pizzorno et al. 2019).”
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Andrade, S., Ramalho, M. J., Loureiro, J. A., & Pereira, M. D. C. (2021) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2021.116141 · Cited by 83
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“Currently LAI development has mostly been viewed as a lifecycle product extension opportunity, where the existing oral drug molecules were repurposed for novel use as LAI to improve patient experience, leveraging the abundance of available information on clinical pharmacokinetics as well as preclinical and clinical sa…”
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“Besides the importance of the efficacy of the prepared compounds against the respective viruses, cytotoxic effect of these antiviral agents on the human cells is also critical [112].”
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Cherian, S., Agrawal, M., Basu, A., Abraham, P., Gangakhedkar, R., & Bhargava, B. (2020) · The Indian Journal of Medical Research · doi:10.4103/ijmr.ijmr_585_20 · Cited by 59
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“Hence, the development of innovative antiviral drugs is required to better treat IAV pneumonia (Pizzorno et al , 2019).”
Eldesouky, H. E., Salama, E. A., Lanman, N. A., Hazbun, T. R., & Seleem, M. N. (2020) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00684-20 · Cited by 56
Virus-host interaction networks as new antiviral drug targets for IAV and SARS-CoV-2
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Nannou, C. I., Ofrydopoulou, A., Εvgenidou, Ε., Heath, D., Heath, E., & Lambropoulou, D. A. (2019) · Trends in Environmental Analytical Chemistry · doi:10.1016/j.teac.2019.e00071 · Cited by 55
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“A randomized placebo-controlled phase II clinical trial (NCT02056340) aimed at evaluating the potential effect of atorvastatin to reduce the severity of illness in influenza-infected patients is currently underway (31) .”
BackgroundMono- and combinational drug therapies for global viral pandemic preparedness
Ianevski, A., Yao, R., Simonsen, R. M., Myhre, V., Ravlo, E., Kaynova, G. D., Žusinaite, E., White, J. M., Polyak, S. J., Oksenych, V., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104112 · Cited by 36
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“For COVID-19, several recent studies have reported the computational screening of inhibitors for specific single targets, such as either the main protease (the aforementioned 3CLpro/Mpro) or the spike protein (Shiryaev et al., 2017; Botta et al., 2018; Pizzorno et al., 2019; Ton et al., 2020; Wang, 2020; Zhang D.-h. e…”
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“Approved or candidate drugs with repurposing potential as antiviral agents exist for a number of emerging viruses for which urgent, cost-effective therapeutic solutions are required, including influenza virus [46], Ebola [47], HCV [48], Zika virus [49], Japanese encephalitis virus (JEV) [50], human cytomegalovirus [51…”
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“Several recent investigations demonstrated that some antibiotics from bacterial origin display interesting antiviral properties [13] representing a unique example of drug repurposing [14].”
BackgroundDrugRepV: a compendium of repurposed drugs and chemicals targeting epidemic and pandemic viruses
Rajput, A., Kumar, A., Megha, K., Thakur, A., & Kumar, M. (2020) · Briefings in Bioinformatics · doi:10.1093/bib/bbaa421 · Cited by 24
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“Vaccine, M2 ion channel inhibitors and neuraminidase inhibitors are most used for treatment of IAV infection [6].”
BackgroundDurdağı, S., Aksoydan, B., Doğan, B., Şahin, K., Shahraki, A., & İyison, N. B. (2020) · ChemRxiv · doi:10.26434/chemrxiv.12032712.v2 · Cited by 22
New Host-Directed Therapeutics for the Treatment of Clostridioides difficile Infection
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“One effective strategy is drug repurposing, which involves finding new uses for existing Food and Drug Administration (FDA)approved drugs (Strittmatter, 2014; Pushpakom et al., 2018; Pizzorno et al., 2019).”
BackgroundRepurposing of approved drug molecules for viral infectious diseases: a molecular modelling approach
Kumar, N., Sarma, H., & Sastry, G. N. (2021) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2021.1905558 · Cited by 22
“…LASV (Peilin et al., 2018; Zhang et al., 2019), IAV (Zhe et al., 2020), SARS-CoV (Jyotisha et al., 2021; Riva et al., 2020; Wang et al., 2020) using various drug repurposing, structure-based virtual screening as well as the experimental approaches (Mercorelli et al., 2018; Pizzorno et al., 2019).”
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“Though drug repurposing is sometimes based on chance observations, target-based repurposing depends on a prior understanding of the specific molecular or cellular element that the proposed drug recognizes (Pizzorno et al., 2019).”
Host-HIV-1 Interactome: A Quest for Novel Therapeutic Intervention
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“Furthermore, combining the evolving VH PPI information with the druggable interactions revealed a very large potential of drug repurposing for the discovery of molecules with antiviral activity [57].”
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“Thus, it can be a viable approach to accelerate the development of novel drug compounds and helps bypass several steps in the drug development process (Pizzorno et al. 2019) and works as a stopgap measure.”
Durdağı, S., Aksoydan, B., Doğan, B., Şahin, K., & Shahraki, A. (2020) · ChemRxiv · doi:10.26434/chemrxiv.12032712.v1 · Cited by 17
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“Drug repurposing has emerged as a powerful tool that reduces time and cost [39].”
Durdağı, S., Orhan, M. D., Aksoydan, B., Calis, S., Başar, B. D., Şahin, K., Shahraki, A., İyison, N. B., & Avşar, T. (2021) · Molecular Informatics · doi:10.1002/minf.202100062 · Cited by 16
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“Gibbs Free Energy (Kcal/mol)”
Drugs, host proteins and viral proteins: how their promiscuities shape antiviral design
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“…treatment), dapivirine (phase III anti-HIV drug), metformin (approved type 2 diabetes drug), lisinopril (anti-hypertensive drug), dorzolamide (approved anti-glaucoma drug), midodrine (approved anti-hypotensive drug), and diltiazem (approved anti-hypertensive drug) are prominent examples [96].”
Overview of Antiviral Drug Discovery and Development: Viral Versus Host Targets
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“A recent example is the repositioning of drugs to treat SARS-CoV-2 infection since the onset of the pandemic [11-13].”
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Retracted
Metadata
- Authors
- Pizzorno, A., Padey, B., Terrier, O., & Rosa-Calatrava, M.
- Affiliations
- Lyon 1 Université (FR)
- Corresponding author
- Terrier, Olivier
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2019-03-19
- Volume
- 10
- Pages
- 531-531
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC6434107
- OpenAlex
- W2923800168
- Cited by
- 122
- References
- 117
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 12 · 2023: 11 · 2022: 17 · 2021: 24 · 2020: 38 · 2019: 5
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Région Auvergne-Rhône-Alpes
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Keywords
- drug repurposing, influenza virus, antiviral agents, host-targeted antivirals, antiviral resistance, virtual screening, antiviral drug discovery
- MeSH terms
- Animals, Antiviral Agents, Humans, Influenza, Human, Orthomyxoviridae, Orthomyxoviridae Infections, Drug Repositioning
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