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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Drug combinations have been utilized efficiently to treat various bacterial and viral infections and cancer.
“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<i>Candida auris</i>and displays potent synergistic interactions with azole drugs (2020) · cites this paper as [20]
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“In that regard, the relatively recent detection of localized clusters of NA inhibitor-resistant H1N1pdm09 viruses harboring the H274Y mutation combined or not with I222R/V NA substitutions (22, 23) strengthens the importance of continuous surveillance.”
BackgroundHung, I. F., To, K. K., Chan, J. F., Cheng, V. C., Liu, K. S. H., Tam, A. R., Chan, T.-C., Zhang, J., Li, P., Wong, T.-L., et al. (2016) · CHEST Journal · doi:10.1016/j.chest.2016.11.012 · Cited by 126 · cited 1× · see citing works
“In a clinical trial enrolling hospitalized patients infected by influenza A(H3N2), combination therapy with naproxen, oseltamivir, and clarithromycin showed improved efficacy in terms of hospital stay duration and patient mortality, when compared to oseltamivir treatment alone (118).”
BackgroundOprea, T. I., Nielsen, S. K., Ursu, O., Yang, J. J., Taboureau, O., Mathias, S. L., Kouskoumvekaki, I. A., Sklar, L. A., & Bologa, C. (2011) · Molecular Informatics · doi:10.1002/minf.201100023 · Cited by 114 · cited 1× · see citing works
“In that regard, proper mining of biological, chemical and clinical datasets, has proved effective in unveiling novel relationships (65, 66).”
BackgroundShi, X., Zhou, W. M., Huang, H., Zhu, H., Zhou, P., Zhu, H., & Ju, D. (2013) · Critical Care · doi:10.1186/cc13171 · Cited by 108 · see citing works
Generation and characterization of influenza A viruses with altered polymerase fidelity
Cheung, P. P., Watson, S. J., Choy, K.-T., Sia, S. F., Wong, D., Poon, L. L. M., Kellam, P., Guan, Y., Peiris, M. J. S., & Yen, H. (2014) · Nature Communications · doi:10.1038/ncomms5794 · Cited by 107 · cited 1× · see citing works
“However, despite the apparent high threshold for drug resistance (24) and broad-spectrum antiviral potential notably validated in the context of recent Ebola virus outbreaks (25), recent results of Phase II/III randomized trials on its therapeutic efficacy against uncomplicated influenza were not completely conclusive…”
Allarakhia, M. (2013) · Drug Design Development and Therapy · doi:10.2147/dddt.s46289 · Cited by 103 · see citing works
Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza
Budd, A. C., Alleva, L. M., Alsharifi, M., Koskinen, A. M. L., Smythe, V., Müllbacher, A., Wood, J. T., & Clark, I. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00219-07 · Cited by 101 · see citing works
Treating Influenza Infection, From Now and Into the Future
Davidson, S. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01946 · Cited by 94 · cited 1× · see citing works
“As most alternative antiviral strategies for the treatment of influenza infections, including those related to drug repurposing and targeting the host instead of viral determinants, an emerging trend consists to propose innovative therapies that combine classic antivirals with host-targeting drugs, which starts to sho…”
BackgroundRestivo, V., Costantino, C., Bono, S. E., Maniglia, M., Marchese, V., Ventura, G., Casuccio, A., Tramuto, F., & Vitale, F. M. (2017) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2017.1321722 · Cited by 92 · cited 1× · see citing works
“Influenza vaccination constitutes the most effective strategy to prevent seasonal flu and its clinical complications, mainly among high-risk populations such as very young children, the elderly, pregnant women, immunocompromised patients as well as people with obesity, diabetes, or cardiorespiratory comorbidities (6,…”
BackgroundBelardo, G., Cenciarelli, O., Frazia, S. L., Rossignol, J. F., & Santoro, M. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.03947-14 · Cited by 91 · cited 1× · see citing works
“have demonstrated, in cell culture-based assays using different human and avian models, that the combination of NA inhibitors and nitazoxanide presents synergistic anti-influenza effects (117).”
BackgroundVenkatesan, S., Myles, P. R., Leonardi‐Bee, J., Muthuri, S. G., Masri, M. A., Andrews, N. J., Bantar, C., Dubnov‐Raz, G., Gérardin, P., Koay, E. S.-C., et al. (2017) · Clinical Infectious Diseases · doi:10.1093/cid/cix127 · Cited by 91 · cited 1× · see citing works
“a moderate efficacy of NA inhibitor treatment in reducing symptom duration, pneumonia, hospitalization and mortality, especially when administered within 48 h from symptom onset (18, 19).”
BackgroundIn Vitroandin VivoActivities of T-705 and Oseltamivir against Influenza Virus
Takahashi, K., Furuta, Y., Fukuda, Y., Kuno, M., Kamiyama, T., Kozaki, K., Nomura, N., Egawa, H., Minami, S., & Shiraki, K. (2003) · Antiviral chemistry & chemotherapy · doi:10.1177/095632020301400502 · Cited by 90 · see citing works
Akpovwa, H. (2016) · Cell Biochemistry and Function · doi:10.1002/cbf.3182 · Cited by 88 · cited 1× · see citing works
“For example, chloroquine, a major antimalarial drug, has been proposed for the treatment of filoviral infections, and more largely for the treatment of other emerging pathogens, as it targets endosomal acidification, a pivotal step in the replication cycle of a large number of viruses (73, 74).”
BackgroundMechanisms of Action and Efficacy of Statins against Influenza
Mehrbod, P., Omar, A. R., Bejo, M. H., Haghani, A., & Ideris, A. (2014) · BioMed Research International · doi:10.1155/2014/872370 · Cited by 87 · see citing works
Obatoclax, Saliphenylhalamide, and Gemcitabine Inhibit Influenza A Virus Infection
Denisova, O. V., Kakkola, L., Feng, L., Stenman, J. J. E., Nagaraj, A. S., Lampe, J. W., Yadav, B., Aittokallio, T. A., Kaukinen, P., Ahola, T., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.392142 · Cited by 85 · see citing works
Influenza treatment and prophylaxis with neuraminidase inhibitors: a review
Holodniy, M., & Kamali, A. (2013) · Infection and Drug Resistance · doi:10.2147/idr.s36601 · Cited by 83 · cited 2× · see citing works
“Even if nowadays the prevalence of drug-resistance in circulating strains is quite low (≤1%), evidence form pre-2009 seasonal strains has proved that, given the appropriate conditions, resistance could rapidly disseminate to attain a prevalence of 90–100% (17, 21).”
BackgroundРабинович, С. А., Baldini, J. T., & Bannister, R. M. (1969) · The American Journal of the Medical Sciences · doi:10.1097/00000441-196905000-00005 · Cited by 79 · see citing works
Moseley, C. E., Webster, R. G., & Aldridge, J. R. (2010) · Influenza and Other Respiratory Viruses · doi:10.1111/j.1750-2659.2010.00155.x · Cited by 78 · see citing works
Pharmacologic Inhibition of COX-1 and COX-2 in Influenza A Viral Infection in Mice
Carey, M. A., Bradbury, J. A., Rebolloso, Y. D., Graves, J. P., Zeldin, D. C., & Germolec, D. R. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011610 · Cited by 77 · see citing works
McKimm‐Breschkin, J. L., Jiang, S., Hui, D. S. C., Beigel, J. H., Govorkova, E. A., & Lee, N. L. S. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.11.013 · Cited by 76 · cited 1× · see citing works
“However, despite the apparent high threshold for drug resistance (24) and broad-spectrum antiviral potential notably validated in the context of recent Ebola virus outbreaks (25), recent results of Phase II/III randomized trials on its therapeutic efficacy against uncomplicated influenza were not completely conclusive…”
Widespread use of neuraminidase inhibitors in Japan
Sugaya, N. (2011) · Journal of Infection and Chemotherapy · doi:10.1007/s10156-011-0288-0 · Cited by 74 · cited 1× · see citing works
“Although their use is mostly focused on the treatment of severely ill patients and the immunocompromised, some countries, including the USA and Japan, regularly resort to antivirals for the management of uncomplicated influenza in otherwise healthy patients (11, 12).”
BackgroundRepurposing Kinase Inhibitors as Antiviral Agents to Control Influenza A Virus Replication
Perwitasari, O., Yan, X., O’Donnell, J., Johnson, S. K., & Tripp, R. A. (2015) · Assay and Drug Development Technologies · doi:10.1089/adt.2015.0003.drrr · Cited by 71 · see citing works
Gene Expression Signature-Based Screening Identifies New Broadly Effective Influenza A Antivirals
Josset, L., Textoris, J., Loriod, B., Ferraris, O., Moulés, V., Lina, B., Nguyen, C., Diaz, J., & Rosa‐Calatrava, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013169 · Cited by 69 · cited 2× · see citing works
“In a proof-of-concept study using an in vitro model of infection, we postulated that host global gene expression profiling can be considered as a “fingerprint” or signature of any specific cell state, including during infection or drug treatment, and hypothesized that the screening of databases for compounds that coun…”
BackgroundSelf-citationGg, J., Muldoon, R. L., & Akers, L. W. (1963) · PubMed · Cited by 67 · see citing works
Cichońska, A., Rousu, J., & Aittokallio, T. A. (2015) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2015.1096926 · Cited by 65 · cited 1× · see citing works
“These in silico methods include the screening of chemical, biological, and text databases, analysis of quantitative structure-activity relationships, pharmacophores, homology models, and other molecular modeling approaches as well as network analysis of biological functions, machine learning and almost any other analy…”
MethodSystematic Drug Repurposing Through Text Mining
Tari, L., & Patel, J. H. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-0709-0_14 · Cited by 63 · see citing works
Schräder, T., Dudek, S. E., Schreiber, A., Ehrhardt, C., Planz, O., & Ludwig, S. (2018) · Antiviral Research · doi:10.1016/j.antiviral.2018.07.006 · Cited by 63 · see citing works
Pizzorno, A., Terrier, O., de Lamballerie, C. N., Julien, T., Padey, B., Traversier, A., Roche, M., Hamelin, M., Rhéaume, C., Croze, S., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00060 · Cited by 63 · cited 2× · see citing works
“In the context of the evaluation of the antiviral activity of diltiazem in the reconstituted human airway epithelium model MucilAir, our group demonstrated that the diltiazem-oseltamivir combination treatment conferred a greater reduction of apical viral titers than that was measured with the same-dose monotherapy, wi…”
BackgroundSelf-citationTilmanis, D., van Baalen, C., Oh, D. Y., Rossignol, J., & Hurt, A. C. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.10.002 · Cited by 62 · cited 1× · see citing works
“This drug presents potent antiviral activity against a large panel of circulating strains (82).”
BackgroundPre-Admission Statin Use and In-Hospital Severity of 2009 Pandemic Influenza A(H1N1) Disease
Brett, S. J., Myles, P. R., Lim, W. S., Enstone, J. E., Bannister, B. A., Semple, M. G., Read, R. C., Taylor, B. L., McMenamin, J., Nicholson, K. G., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018120 · Cited by 60 · cited 1× · see citing works
“On the other hand, a few but not all observational studies highlighted an association between statin treatment with up to 41% reduction of 30-day all-cause mortality in patients hospitalized with laboratory-confirmed seasonal influenza (103) (104) (105) .”
BackgroundThe Effect of Rosuvastatin in a Murine Model of Influenza A Infection
Radigan, K. A., Urich, D., Misharin, A. V., Chiarella, S. E., Soberanes, S., Gonzalez, A., Perlman, H., Wunderink, R. G., Budinger, G. R. S., & Mutlu, G. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035788 · Cited by 53 · cited 1× · see citing works
“Although many mouse and observational studies account for the protective role of statins in pneumonia, most in vivo studies reported so far failed to clearly demonstrate such a beneficial effect in the specific context of influenza infection (99) (100) (101) (102) .”
BackgroundSidders, B. S., Karlsson, A., Kitching, L., Torella, R., Karila, P., & Phelan, A. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.07.016 · Cited by 52 · see citing works
Tarus, B., Chevalier, C., Richard, C.-A., Delmas, B., Primo, C. D., & Slama‐Schwok, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030038 · Cited by 49 · cited 2× · see citing works
“P h a se II (N C T 0 3 2 1 2 7 1 6 ) ( 9 8 ) Frontiers in Immunology | www.frontiersin.org 7 March 2019 | Volume 10 | Article 531 site of NP structure, has identified naproxen, a known inhibitor of inducible cyclooxygenase type 2 (COX-2) commonly used as non-steroidal anti-inflammatory drug.”
BackgroundNeuraminidase inhibitors: who, when, where?
Nguyen‐Van‐Tam, J. S., Venkatesan, S., Muthuri, S. G., & Myles, P. R. (2014) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2014.11.020 · Cited by 48 · cited 1× · see citing works
“Although their use is mostly focused on the treatment of severely ill patients and the immunocompromised, some countries, including the USA and Japan, regularly resort to antivirals for the management of uncomplicated influenza in otherwise healthy patients (11, 12).”
BackgroundDilly, S., Fotso, A. F., Lejal, N., Zedda, G., Chebbo, M., Rahman, F., Companys, S., Bertrand, H. C., Vidić, J., Noiray, M., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00557 · Cited by 40 · cited 2× · see citing works
“P h a se II (N C T 0 3 2 1 2 7 1 6 ) ( 9 8 ) Frontiers in Immunology | www.frontiersin.org 7 March 2019 | Volume 10 | Article 531 site of NP structure, has identified naproxen, a known inhibitor of inducible cyclooxygenase type 2 (COX-2) commonly used as non-steroidal anti-inflammatory drug.”
BackgroundDrug Repositioning: Playing Dirty to Kill Pain
Bastos, L. F. S., & Coelho, M. M. (2013) · CNS Drugs · doi:10.1007/s40263-013-0128-0 · Cited by 36 · cited 1× · see citing works
“Indeed, despite this approach has been questioned due to the fact that the expected altered phenotype readout as a surrogate of an exploitable biological effect induced by the drug candidate might account for an important number of false positive “hits,” it is nonetheless true that the contribution of highthroughput p…”
BackgroundThe development and manufacture of influenza vaccines
Buckland, B. C. (2015) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2015.1026497 · Cited by 35 · cited 1× · see citing works
“Moreover, the length of the current vaccine manufacturing process (at least 6 months to produce sufficiently large vaccine quantities) demands continual strain selection to be done approximately 8 months before the next flu season (6, 8).”
BackgroundEscuret, V., Cornu, C., Boutitie, F., Enouf, V., Mosnier, A., Bouscambert‐Duchamp, M., Gaillard, S., Duval, X., Blanchon, T., Leport, C., et al. (2012) · Antiviral Research · doi:10.1016/j.antiviral.2012.08.002 · Cited by 35 · cited 1× · see citing works
“A clinical trial was conducted during the A(H1N1)pdm09 pandemic in 2009-2010 (COMBINA trial NCT00830323) and failed to demonstrate whether oseltamivir/zanamivir combination therapy improved or reduced the effectiveness of oseltamivir alone in the treatment of influenza infections in community patients (115).”
MethodIdentification of Novel Genes and Pathways Regulating SREBP Transcriptional Activity
Chatterjee, S., Szustakowski, J. D., Nirmala, N., Mickanin, C., Labow, M., Nohturfft, A., Dev, K. K., & Sivasankaran, R. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005197 · Cited by 35 · cited 1× · see citing works
“In that regard, proper mining of biological, chemical and clinical datasets, has proved effective in unveiling novel relationships (65, 66).”
BackgroundDrug Repurposing for Epigenetic Targets Guided by Computational Methods
Naveja, J. J., Dueñas‐González, A., & Medina‐Franco, J. L. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802808-7.00012-5 · Cited by 34 · see citing works
Clinical Regimens of Favipiravir Inhibit Zika Virus Replication in the Hollow-Fiber Infection Model
de Mello, C. P. P., Tao, X., Kim, T., Vicchiarelli, M., Bulitta, J. B., Kaushik, A. K., & Brown, A. N. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00967-18 · Cited by 32 · see citing works
Carrat, F., Duval, X., Tubach, F., Mosnier, A., van der Werf, S., Tibi, A., Blanchon, T., Leport, C., Flahault, A., Mentré, F., et al. (2012) · Antiviral Therapy · doi:10.3851/imp2128 · Cited by 31 · cited 1× · see citing works
“Other clinical investigations have shown a greater effectiveness of such combination therapy to reduce influenza transmissibility (116).”
BackgroundHu, Y., Zhang, J., Musharrafieh, R. G., Ma, C., Hau, R. K., & Wang, J. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.07.016 · Cited by 31 · see citing works
Kumaki, Y., Morrey, J. D., & Barnard, D. L. (2012) · Future Virology · doi:10.2217/fvl.12.71 · Cited by 30 · cited 1× · see citing works
“Although many mouse and observational studies account for the protective role of statins in pneumonia, most in vivo studies reported so far failed to clearly demonstrate such a beneficial effect in the specific context of influenza infection (99) (100) (101) (102) .”
BackgroundRepurposing drugs for use against Zika virus infection
Devillers, J. (2018) · SAR and QSAR in environmental research · doi:10.1080/1062936x.2017.1411642 · Cited by 30 · cited 2× · see citing works
“Another interesting illustration is the previously cited example of favipiravir, which proved its repurposing potential for the treatment of Zika or Ebola viral infections (25, 43, 75).”
BackgroundBelser, J. A., Szretter, K. J., Katz, J. M., & Tumpey, T. M. (2013) · Virology · doi:10.1016/j.virol.2013.01.017 · Cited by 29 · cited 1× · see citing works
“Although many mouse and observational studies account for the protective role of statins in pneumonia, most in vivo studies reported so far failed to clearly demonstrate such a beneficial effect in the specific context of influenza infection (99) (100) (101) (102) .”
BackgroundDrug Repurposing Identifies Inhibitors of Oseltamivir‐Resistant Influenza Viruses
Bao, J., Marathe, B. M., Govorkova, E. A., & Zheng, J. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201511361 · Cited by 28 · see citing works
How academic labs can approach the drug discovery process as a way to synergize with big pharma
Loregian, A., & Palù, G. (2013) · Trends in Microbiology · doi:10.1016/j.tim.2013.03.006 · Cited by 27 · cited 1× · see citing works
“In that regard, many well-annotated collections of smallmolecule libraries could be readily made available through different collaborative and/or commercial partnerships in order to accelerate drug repurposing through hypothesis biased or unbiased phenotypic screening [reviewed in (54) (55) (56) (57) ].”
BackgroundOld Drugs Losing Effectiveness Against Flu; Could Statins Fill Gap?
Enserink, M. (2005) · Science · doi:10.1126/science.309.5743.1976a · Cited by 26 · cited 1× · see citing works
“On the other hand, a few but not all observational studies highlighted an association between statin treatment with up to 41% reduction of 30-day all-cause mortality in patients hospitalized with laboratory-confirmed seasonal influenza (103) (104) (105) .”
BackgroundScheuch, G., Canisius, S., Nocker, K., Hofmann, T., Naumann, R., Pleschka, S., Ludwig, S., Welte, T., & Planz, O. (2018) · Emerging Microbes & Infections · doi:10.1038/s41426-018-0023-3 · Cited by 26 · cited 1× · see citing works
“More recently, a Phase II proof-of-concept study comparing LASAG versus placebo in patients with severe influenza (all patients receiving Tamiflu as standard of care treatment) demonstrated that aerosolized LASAG improved the time to symptom alleviation compared to placebo, despite the absence of a statistically signi…”
BackgroundClinician-initiated research on treating the host response to pandemic influenza
Fedson, D. S. (2017) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2017.1378292 · Cited by 24 · see citing works
Droebner, K., Haasbach, E., Dudek, S. E., Scheuch, G., Nocker, K., Canisius, S., Ehrhardt, C., von Degenfeld, G., Ludwig, S., & Planz, O. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.02130 · Cited by 23 · cited 1× · see citing works
“In a mouse infection model, inhalation of LASAG resulted in reduced lung viral titers and protection of mice from lethal infection (85).”
BackgroundPizzorno, A., Abed, Y., Rhéaume, C., & Boivin, G. (2014) · Antiviral Research · doi:10.1016/j.antiviral.2014.02.017 · Cited by 14 · cited 1× · see citing works
“For example, in a mouse model, the combination of oseltamivir with zanamivir was shown to be not superior to zanamivir monotherapy in the context of influenza A(H3N2) or A(H1N1)pdm09 infection (114).”
BackgroundSelf-citationRohini, K., & Veerappapillai, S. (2018) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-018-0844-7 · Cited by 14 · see citing works
Khurana, S. (2018) · Vaccines · doi:10.3390/vaccines6020024 · Cited by 13 · see citing works
Sunagawa, S., Higa, F., Cash, H. L., Tateyama, M., Uno, T., & Fujita, J. (2012) · Influenza and Other Respiratory Viruses · doi:10.1111/j.1750-2659.2012.00351.x · Cited by 11 · cited 1× · see citing works
“Additionally, inhaled laninamivir, a single-dose long lasting NA inhibitor, is approved in Japan for the prevention and treatment of influenza A and B in both adult and pediatric patients (16).”
BackgroundWill omics help to cure the flu?
Ludwig, S. (2014) · Trends in Microbiology · doi:10.1016/j.tim.2014.03.003 · Cited by 4 · cited 1× · see citing works
“Despite many interesting omics-based approaches (76) or high-throughput screening of specific drug libraries, such as kinase inhibitors (77), no anti-influenza agent issued from drug repurposing has yet reached regulatory market approval.”
Background
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Discovery and development of safe-in-man broad-spectrum antiviral agents
Andersen, P. I., Ianevski, A., Lysvand, H., Vitkauskienė, A., Oksenych, V., Bjørås, M., Telling, K., Lutsar, I., Dumpis, U., Irie, Y., et al. (2020) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2020.02.018 · Cited by 272 · see citing works
“…opportunities, including a substantially higher probability of success to market as compared with developing new virus-specific drugs and vaccines, and a significantly reduced cost and timeline to clinical availability (Ianevski et al., 2019; Pizzorno et al., 2019; Zheng et al., 2018).”
Host-Directed Antiviral Therapy
Kumar, N., Sharma, S., Kumar, R., Tripathi, B. N., Barua, S., Ly, H., & Rouse, B. T. (2020) · Clinical Microbiology Reviews · doi:10.1128/cmr.00168-19 · Cited by 281 · see citing works
“multiple host factors and pathways that are supportive of virus replication (299, 300).”
BackgroundAntiviral Approaches against Influenza Virus
Kumari, R., Sharma, S. D., Kumar, A., Ende, Z. S., Mishina, M., Wang, Y., Falls, Z., Samudrala, R., Pohl, J., Knight, P. R., et al. (2023) · Clinical Microbiology Reviews · doi:10.1128/cmr.00040-22 · Cited by 172 · see citing works
“It was demonstrated in vitro and in vivo in a mouse model that Diltiazem modulates host antiviral genes in vitro and in vivo in a mouse model, and cotreatment with Oseltamivir enhanced the antiviral efficacy (362).”
BackgroundInhibitors of VPS34 and fatty-acid metabolism suppress SARS-CoV-2 replication
Williams, C. G., Jureka, A. S., Silvas, J. A., Nicolini, A. M., Chvatal, S. A., Carlson-Stevermer, J., Oki, J., Holden, K., & Basler, C. F. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109479 · Cited by 143 · see citing works
“Repurposing drugs developed for other diseases and conditions may provide a shortcut to antiviral development (Garcı́a-Serradilla et al., 2019; Li and De Clercq, 2020; Pizzorno et al., 2019; Saini et al., 2020).”
Potential Antiviral Options against SARS-CoV-2 Infection
Ianevski, A., Yao, R., Fenstad, M. H., Biza, S., Žusinaite, E., Reisberg, T., Lysvand, H., Løseth, K., Landsem, V. M., Malmring, J. F., et al. (2020) · Viruses · doi:10.3390/v12060642 · Cited by 107 · see citing works
Medicinal plants: Treasure for antiviral drug discovery
Ali, S. I., Sheikh, W. M., Rather, M. A., Venkatesalu, V., Bashir, S. M., & Nabi, S. U. (2021) · Phytotherapy Research · doi:10.1002/ptr.7039 · Cited by 100 · see citing works
Current Status of COVID-19 Therapies and Drug Repositioning Applications
Altay, O., Mohammadi, E., Lam, S., Turkez, H., Boren, J., Nielsen, J., Uhlen, M., & Mardinoglu, A. (2020) · iScience · doi:10.1016/j.isci.2020.101303 · Cited by 98 · see citing works
“Recently, dornase alfa as a recombinant human deoxyribonuclease I is considered for clinical trials of patients with severe COVID-19 who mostly progress to an ARDS condition: hypoxemic respiratory failure associated with neutrophilia and neutrophil infiltration in the lungs, thick mucus in bronchi, and bronchiectasis…”
Jiang, C., Yao, X., Zhao, Y., Wu, J., Huang, P., Pan, C., Liu, S., & Pan, C. (2020) · Microbes and Infection · doi:10.1016/j.micinf.2020.05.005 · Cited by 98 · see citing works
NF-κB Signaling and Inflammation—Drug Repurposing to Treat Inflammatory Disorders?
Roberti, A., Chaffey, L., & Greaves, D. R. (2022) · Biology · doi:10.3390/biology11030372 · Cited by 103 · see citing works
“Target-based drug repurposing requires knowledge of the molecular target of candidate drugs, whereas phenotypic screens do not rely on extensive scientific knowledge of the mode of action of a drug or the molecular pathology of a disease [64-67].”
BackgroundVerma, A. K., Kumar, V., Singh, S., Goswami, B. C., Camps, I., Sekar, A., Yoon, S., & Lee, K. W. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111356 · Cited by 95 · see citing works
“This paper reports the state of-the-art antiviral choices against COVID-19, with a specific focus on the recent advances of Ayurvedic antiviral medication repurposing procedures and their potential therapeutic suggestion [5].”
BackgroundParvez, M. S. A., Karim, M. A., Hasan, M., Jaman, J., Karim, Z., Tahsin, T., Hasan, M. N., & Hosen, M. J. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.09.098 · Cited by 87 · see citing works
Drug targets for COVID-19 therapeutics: Ongoing global efforts
Saxena, A. (2020) · Journal of Biosciences · doi:10.1007/s12038-020-00067-w · Cited by 83 · see citing works
“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).”
BackgroundLiposomes as biomembrane models: Biophysical techniques for drug-membrane interaction studies
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 81 · see citing works
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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…”
BackgroundBlum, V. F., Cimerman, S., Hunter, J., Tierno, P. F. G. M. M., Lacerda, A. L. T., Soeiro, A. D. M., Cardoso, F., Bellei, N., Maricato, J. T., Mantovani, N., et al. (2021) · EClinicalMedicine · doi:10.1016/j.eclinm.2021.100981 · Cited by 66 · see citing works
“NTZ has been clinically evaluated in treating influenza viruses with selective blockage of viral hemagglutinin’s maturation, which impairs its intracellular trafficking and the insertion of viral protein in the host membrane [26,27].”
Dose prediction for repurposing nitazoxanide in SARS‐CoV‐2 treatment or chemoprophylaxis
Rajoli, R. K. R., Pertinez, H. E., Arshad, U., Box, H., Tatham, L. M., Curley, P., Neary, M., Sharp, J., Liptrott, N. J., Valentijn, A., et al. (2020) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14619 · Cited by 58 · see citing works
Anti-viral activity of thiazole derivatives: an updated patent review
Farghaly, T. A., Alsaedi, A. M. R., Alenazi, N. A., & Harras, M. F. (2022) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2022.2067477 · Cited by 60 · see citing works
“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].”
BackgroundPerspectives for repurposing drugs for the coronavirus disease 2019
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 · see citing works
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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 · see citing works
Virus-host interaction networks as new antiviral drug targets for IAV and SARS-CoV-2
Chen, N., Zhang, B., Deng, L., Liang, B., & Ping, J. (2022) · Emerging Microbes & Infections · doi:10.1080/22221751.2022.2071175 · Cited by 57 · see citing works
“for developing new antiviral strategies with novel mechanisms of action and with reduced drug resistance potential [14,15].”
BackgroundAnalytical strategies for the determination of antiviral drugs in the aquatic environment
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 · see citing works
Luo, Z., Ang, M. J. Y., Chan, S. Y., Yi, Z., Goh, Y. Y., Yan, S., Tao, J., Liu, K., Li, X., Zhang, H., et al. (2020) · Research · doi:10.34133/2020/6925296 · Cited by 49 · see citing works
“As COVID-19 is a viral infection, the most obvious choices for repurposed drugs come from known antiviral drugs [102].”
BackgroundKwofie, S. K., Broni, E., Asiedu, S. O., Kwarko, G. B., Dankwa, B., Enninful, K. S., Tiburu, E. K., & Wilson, M. D. (2021) · Molecules · doi:10.3390/molecules26020406 · Cited by 49 · see citing works
“This is to identify potential polypharmacological antiviral compounds targeting both proteins [46,47] with novel scaffolds to augment the design of next-generation inhibitors against the cell entry and replication of SARS-CoV-2.”
BackgroundTerrier, O., Dilly, S., Pizzorno, A., Chalupská, D., Humpolíčková, J., Bouřa, E., Berenbaum, F., Quideau, S., Lina, B., Fève, B., et al. (2021) · Molecules · doi:10.3390/molecules26092593 · Cited by 45 · see citing works
“In the present pandemic context, we aim at impeding N association with viral RNA and induced N oligomerization with repurposed drugs [22].”
BackgroundSelf-citationExpanding the activity spectrum of antiviral agents
Ianevski, A., Andersen, P. I., Merits, A., Bjørås, M., & Kainov, D. E. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.04.006 · Cited by 42 · see citing works
Inhaled biguanides and mTOR inhibition for influenza and coronavirus (Review)
Lehrer, S. P. (2020) · World Academy of Sciences Journal · doi:10.3892/wasj.2020.42 · Cited by 40 · see citing works
“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 · see citing works
“It takes approximately 13–15 years and 2 billion USD to develop a new antiviral drug from an antiviral agent (Pizzorno et al., 2019).”
Eldesouky, H. E., Lanman, N. A., Hazbun, T. R., & Seleem, M. N. (2020) · Virulence · doi:10.1080/21505594.2020.1838741 · Cited by 37 · see citing works
In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses
Checkmahomed, L., Padey, B., Pizzorno, A., Terrier, O., Rosa‐Calatrava, M., Abed, Y., Baz, M., & Boivin, G. (2020) · Viruses · doi:10.3390/v12101139 · Cited by 37 · see citing works
“Such synergistic effects were confirmed in the HAE model, for which the physiological relevance and predictive value have been previously described by our group and others [33].”
BackgroundSelf-citationComputational Prediction of Potential Inhibitors of the Main Protease of SARS-CoV-2
Abel, R., Paredes-Ramos, M., Chen, Q., Pérez‐Sánchez, H., Coluzzi, F., Rocco, M., Marchetti, P., Mura, C., Simmaco, M., Bourne, P. E., et al. (2020) · Frontiers in Chemistry · doi:10.3389/fchem.2020.590263 · Cited by 33 · see citing works
“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…”
BackgroundHasan, M., Parvez, M. S. A., Azim, K. F., Imran, M. A. S., Raihan, T., Gulshan, A., Muhit, S., Akhand, M. R. N., Ahmed, S. S. U., & Uddin, M. B. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111742 · Cited by 25 · see citing works
“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…”
Szűcs, Z., Naesens, L. M. J., Stevaert, A., Ostorházi, E., Batta, G., Herczegh, P., & Borbás, A. (2020) · Pharmaceuticals · doi:10.3390/ph13070139 · Cited by 24 · see citing works
“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 · see citing works
Potential antiviral options against SARS-CoV-2 infectionPreprint
Ianevski, A., Yao, R., Fenstad, M. H., Biza, S., Zusinaite, E., Reisberg, T., Lysvand, H., Løseth, K., Landsem, V. M., Malmring, J. F., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.12.091165 · Cited by 24 · see citing works
Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus
Tu, P., Tian, R., Lu, Y., Zhang, Y., Zhu, H., Ling, L., Li, H., & Chen, D. (2020) · Chinese Medicine · doi:10.1186/s13020-020-00415-w · Cited by 22 · see citing works
“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 · see citing works
New Host-Directed Therapeutics for the Treatment of Clostridioides difficile Infection
Andersson, J. A., Peniche, A. G., Galindo, C. L., Boonma, P., Sha, J., Luna, R. A., Savidge, T., Chopra, A. K., & Dann, S. M. (2020) · mBio · doi:10.1128/mbio.00053-20 · Cited by 21 · see citing works
Braun, M., Sharon, E., Unterman, I., Miller, M., Mellul, A., Benenson, S., Vainstein, A., & Tabach, Y. (2020) · iScience · doi:10.1016/j.isci.2020.101384 · Cited by 21 · see citing works
“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 · see citing works
“…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).”
MethodAbbas, G., Yu, J., & Li, G. (2022) · Frontiers in Veterinary Science · doi:10.3389/fvets.2022.933274 · Cited by 20 · see citing works
Applications of machine learning approaches to combat COVID-19: A survey
Tiwari, S. M., Doğan, O., Jabbar, M. A., Shandilya, S. K., Ortiz, F., Bajpai, S., & Banerjee, S. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-99878-9.00014-5 · Cited by 19 · see citing works
“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
Shukla, E., & Chauhan, R. (2019) · Cells · doi:10.3390/cells8101155 · Cited by 17 · see citing works
“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].”
BackgroundLi, R., Zhou, X., Zhou, H., Yang, Z., Jiang, H., Wu, X. Y., Li, W.-J., Qiu, J.-J., Mi, J., Chen, M., et al. (2021) · ACS Omega · doi:10.1021/acsomega.0c05264 · Cited by 18 · see citing works
Sathish, S., Devaraju, P., Julius, A., Sohn, H., & Madhavan, T. (2023) · Chemical Papers · doi:10.1007/s11696-023-03070-1 · Cited by 17 · see citing works
“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 · see citing works
Rajput, A., Thakur, A., Rastogi, A., Choudhury, S., & Kumar, M. (2021) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2021.104677 · Cited by 16 · see citing works
“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 · see citing works
Pavithran, H., Kumavath, R., & Ghosh, P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115922 · Cited by 15 · see citing works
“Gibbs Free Energy (Kcal/mol)”
Drugs, host proteins and viral proteins: how their promiscuities shape antiviral design
Gupta, M. N., & Roy, I. (2020) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12652 · Cited by 15 · see citing works
Almulhim, M. F., Ghasemian, A., Memariani, M., Karami, F., Yassen, A. S. A., Alexiou, A. T., Papadakis, M., & Batiha, G. E. (2025) · Molecular Diversity · doi:10.1007/s11030-025-11131-8 · Cited by 14 · see citing works
“…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
Li, G., & Clercq, E. D. (2021) · Royal Society of Chemistry eBooks · doi:10.1039/9781788016858-00001 · Cited by 14 · see citing works
Kálai, T., Pongracz, J. E., & Mátyus, P. (2022) · Chemistry · doi:10.3390/chemistry4020019 · Cited by 14 · see citing works
Bhattacharjee, A., Ahammad, I., Chowdhury, Z. M., Das, K. C., Keya, C. A., & Salimullah, M. (2022) · Molecular Biotechnology · doi:10.1007/s12033-022-00595-w · Cited by 13 · see citing works
Negru, P. A., Miculas, D. C., Behl, T., Bungău, A. F., Marin, R.-C., & BUNGAU, S. G. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113432 · Cited by 13 · see citing works
“A recent example is the repositioning of drugs to treat SARS-CoV-2 infection since the onset of the pandemic [11-13].”
Broad-spectrum antiviral activity of naproxen: from Influenza A to SARS-CoV-2 CoronavirusPreprint
Terrier, O., Dilly, S., Pizzorno, A., Henri, J., Berenbaum, F., Lina, B., Fève, B., Adnet, F., Sabbah, M., Rosa‐Calatrava, M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.30.069922 · Cited by 13 · see citing works
Self-citationElgammal, Y., Salama, E. A., & Seleem, M. N. (2023) · Medical Mycology · doi:10.1093/mmy/myad081 · Cited by 13 · see citing works
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Low, Z. Y., Wong, K. H., Yip, A. J. W., & Choo, W. S. (2023) · Current Research in Microbial Sciences · doi:10.1016/j.crmicr.2023.100202 · Cited by 11 · see citing works
Kumar, K. S., Ravichandiran, V., & Roy, K. K. (2019) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2019.1651221 · Cited by 11 · see citing works
“…Miner et al., 2019; Miro-Canturri et al., 2019; Nascimento et al., 2019; Neuberger et al., 2019; NowakSliwinska et al., 2019; Pazhayam et al., 2019; Pizzorno et al., 2019; Polamreddy & Gattu, 2019; Regulska et al., 2019; SoriaCastro et al., 2019; Sreekanth et al., 2019; Sukhatme et al., 2019;…”
BackgroundPeterson, J. M., O’Leary, C. A., & Moss, W. N. (2022) · Scientific Reports · doi:10.1038/s41598-021-03767-x · Cited by 11 · see citing works
“Here, a TP occurs when the nucleotide position is paired in the corresponding connectivity table (CT) file and considered paired at the corresponding constraint threshold; a FP occurs when the position is unpaired in (1) TPR = TP”
BackgroundTerrier, O., & Slama‐Schwok, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-981-16-0267-2_8 · Cited by 10 · see citing works
Self-citationAmiroch, S., Irawan, M. I., Mukhlash, I., Faroby, M. H. Z. A., & Nidom, C. A. (2022) · Symmetry · doi:10.3390/sym14061114 · Cited by 9 · see citing works
Farabi, S., Saha, N. R., Hasanuzzaman, M., Khan, N. A., & Haque, M. S. (2020) · Journal of Advanced Biotechnology and Experimental Therapeutics · doi:10.5455/jabet.2020.d159 · Cited by 9 · see citing works
Ji, X., Jin, C., Dong, X., Dixon, M. S., Williams, K. P., & Zheng, W. (2020) · Molecules · doi:10.3390/molecules25173933 · Cited by 9 · see citing works
Targeting Host Dependency Factors: A Paradigm Shift in Antiviral Strategy Against RNA Viruses
Yang, J., Qu, Y., Yuan, Z., Lun, Y., Kuang, J., Shao, T., Qi, Y., Li, Y., & Zhu, L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms27010147 · Cited by 8 · see citing works
“The host protease network presents a similar dilemma; its members play pleiotropic roles in cellular signaling, protein homeostasis, and apoptosis, making the development of inhibitors that are both highly specific and safe a formidable task [70,71].”
Trigueiro-Louro, J. M., dos Santos, L. J., Almeida, F., Correia, V., Brito, R. M. M., & Rebelo‐de‐Andrade, H. (2021) · Virology · doi:10.1016/j.virol.2021.11.001 · Cited by 8 · see citing works
Kadioglu, O., Bahramimehr, F., Dawood, M., Mahmoud, N., Elbadawi, M., Lu, X., Bülbül, Y., Schulz, J. A., Krämer, L., Urschel, M.-K., et al. (2023) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2023.106781 · Cited by 8 · see citing works
Strategies and Challenges to Develop Therapeutic Candidates against COVID-19 Pandemic
Bhatia, R., Ganti, S. S., Narang, R. K., & Rawal, R. K. (2020) · The Open Virology Journal · doi:10.2174/1874357902014010016 · Cited by 8 · see citing works
Phytochemicals as Potential Curative Agents against Viral Infection: A Review
Kumar, A., Singh, A. K., & Tripathi, G. (2020) · Current Organic Chemistry · doi:10.2174/138527282499920091009352 · Cited by 7 · see citing works
IAV inhibits the host antiviral defense mediated by LncRNA-LRIR to enhance viral replication
Chen, N., Jin, J., Zhao, L., Liu, Q., Guo, Y., Deng, L., Liang, B., Zeng, Y., & Ping, J. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.146665 · Cited by 6 · see citing works
Álvarez, C., de Araújo, E. S. A., Baumeister, E. G., Crespo, K. A. N., Kalergis, A. M., Muñoz‐Medina, J. E., Tsukayama, P., & Ugarte‐Gil, C. (2024) · COVID · doi:10.3390/covid4020017 · Cited by 8 · see citing works
Xu, S. B., Esmaeili, S., Ojeda, E. F. C., Goyal, A., White, J. M., Polyak, S. J., & Schiffer, J. T. (2024) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01015-23 · Cited by 5 · see citing works
Current Strategies and Approaches in Combating SARS-CoV-2 Virus that Causes COVID-19
Sivaraman, D., Pradeep, P. S., Manoharan, S. S., Bhat, C. R., Leela, K., & Venugopal, V. (2020) · Letters in Drug Design & Discovery · doi:10.2174/157018081705200403092546 · Cited by 6 · see citing works
Padey, B., Droillard, C., Dulière, V., Fouret, J., de Lamballerie, C. N., Milesi, C., Laurent, E., Brun, P., Traversier, A., Julien, T., et al. (2025) · Antiviral Research · doi:10.1016/j.antiviral.2025.106138 · Cited by 5 · see citing works
Self-citationNatural experiment concept to accelerate the Re-purposing of existing therapeutics for Covid-19
Daughton, C. G. (2020) · Global Epidemiology · doi:10.1016/j.gloepi.2020.100026 · Cited by 5 · see citing works
“Drug repurposing has proved to be a successful enterprise over the years [6,22,24].”
BackgroundEvolution of COVID-19 Pregnancies Treated With Nitazoxanide in a Third-Level Hospital
López, K. Y. E., Calderón, J. M., Ávila, L. D. L. C., Esquivel, M. Á. L., Figueroa, J. M., Contreras, M. J. V., Herrera, J. A., Martínez, O. R. S., López, J. A. M., & Zerón, H. M. (2021) · Cureus · doi:10.7759/cureus.15002 · Cited by 5 · see citing works
“The facts that support its use in the actual pandemic are the following scientific evidence: 1) it inhibits the viral replication of the coronavirus [15], (2) it amplifies the antiviral response of the host by enhancing the pathways of type 1 interferons (IFN-1) when exposed to exogenous cytoplasmic ribonucleic acid […”
BackgroundInfluentialMounadi, N., Nour, H., Abass, K. S., Kouali, M. E., & Chtita, S. (2025) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c00992 · Cited by 4 · see citing works
Perović, V., Stevanović, K. Z., Bukreyeva, N., Paessler, S., Maruyama, J., López-Serrano, S., Darji, A., Senćanski, M., Radošević, D., Berardozzi, S., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094911 · Cited by 4 · see citing works
“Recent reviews have highlighted the potential of this strategy, and investigations into repurposing diverse drug classes [8], among other several antibiotic classes such as macrolides [9] and aminoglycosides [10], have been documented.”
BackgroundEgorov, A. D., Горохов, Я. В., Kuznetsov, M. M., & Borisevich, S. S. (2025) · Russian Chemical Bulletin · doi:10.1007/s11172-025-4579-5 · Cited by 3 · see citing works
Ge, Z., Zhao, C., Xu, Y., Xue, X., Pan, W. X., Zhang, W., Chen, Z., Lin, L., & Tian, D. (2025) · Virology Journal · doi:10.1186/s12985-025-02818-3 · Cited by 3 · see citing works
“Thalidomide for leprosy erythema nodosum and multiple myeloma are typical examples of successful drug function repositioning [21].”
Dřevı́nek, P., Flisiak, R., Nemeş, R. M., Crespo, K. A. N., & Tomasiewicz, K. (2024) · Diagnostics · doi:10.3390/diagnostics14060631 · Cited by 3 · see citing works
“Nonethe-less, evidence indicates an increase in drug resistance due to drug-induced selective pressure [66,177,178], propped by inappropriate use and excessive prescription [67,179].”
BackgroundCOVID-19 Drug Repositioning: Present Status and Prospects
Mohanty, C., Vinod, C., Acharya, S., & Mahapatra, N. (2021) · Studies in systems, decision and control · doi:10.1007/978-3-030-72834-2_19 · Cited by 3 · see citing works
Drug Repurposing for Hematological Malignancies
Michael, A. A., Balakrishnan, P., & Velusamy, T. (2023) · Springer eBooks · doi:10.1007/978-981-19-5399-6_11 · Cited by 3 · see citing works
Kumosani, T., Abbas, A. T., Basheer, B., Hassan, A. M., Yaghmoor, S., Alyahiby, A., Asseri, A. H., Dwivedi, V. D., & Azhar, E. I. (2025) · PLoS ONE · doi:10.1371/journal.pone.0310836 · Cited by 3 · see citing works
Trivedi, J. S., Ghosh, P., & Mitra, D. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.04.096 · Cited by 3 · see citing works
Durdağı, S., Aksoydan, B., Doğan, B., Şahin, K., Shahraki, A., & İyison, N. B. (2020) · ChemRxiv · doi:10.26434/chemrxiv.12032712 · Cited by 3 · see citing works
Tankyrases positively regulate influenza A virus replication via type I interferon response
Bamunuarachchi, G., Vaddadi, K., Liang, Y., Zhu, Z., Dang, Q., Hewawasam, S., & Liu, L. (2025) · Journal of Virology · doi:10.1128/jvi.01298-25 · Cited by 2 · see citing works
“Genome-wide RNAi screening and inhibitor studies for those host factors are of particular importance for current efforts to develop the next generation of anti-influenza drugs (39–41).”
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Unfurling the Potential of Antiviral Agents Aimed for RNA Virus Ailment
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Retracted
- 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
- Physical Sciences › Computer Science › Computational Theory and Mathematics › 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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