{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:44:08Z","timestamp":1790480648858,"version":"4.1.0"},"reference-count":117,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFD0500205, 2018YFD0500100"],"award-info":[{"award-number":["2016YFD0500205, 2018YFD0500100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Fujian Province of China","award":["2016J01090"],"award-info":[{"award-number":["2016J01090"]}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1805231, 32030110, 31602046"],"award-info":[{"award-number":["U1805231, 32030110, 31602046"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Influenza virus is a highly contagious zoonotic respiratory disease that causes seasonal outbreaks each year and unpredictable pandemics occasionally with high morbidity and mortality rates, posing a great threat to public health worldwide. Besides the limited effect of vaccines, the problem is exacerbated by the lack of drugs with strong antiviral activity against all flu strains. Currently, there are two classes of antiviral drugs available that are chemosynthetic and approved against influenza A virus for prophylactic and therapeutic treatment, but the appearance of drug-resistant virus strains is a serious issue that strikes at the core of influenza control. There is therefore an urgent need to develop new antiviral drugs. Many reports have shown that the development of novel bioactive plant extracts and microbial extracts has significant advantages in influenza treatment. This paper comprehensively reviews the development and effects of chemosynthetic drugs, plant extracts, and microbial extracts with influenza antiviral activity, hoping to provide some references for novel antiviral drug design and promising alternative candidates for further anti-influenza drug development.<\/jats:p>","DOI":"10.3390\/molecules26040810","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T12:02:10Z","timestamp":1612440130000},"page":"810","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Development and Effects of Influenza Antiviral Drugs"],"prefix":"10.3390","volume":"26","author":[{"given":"Hang","family":"Yin","sequence":"first","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Chi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sairu","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4274-0563","authenticated-orcid":false,"given":"Ji-Long","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.ympev.2018.01.008","article-title":"In-depth phylodynamics, evolutionary analysis and in silico predictions of universal epitopes of Influenza A subtypes and Influenza B viruses","volume":"121","author":"Salemi","year":"2018","journal-title":"Mol. Phylogenet. Evol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1099\/vir.0.064352-0","article-title":"Pathogenic influenza B virus in the ferret model establishes lower respiratory tract infection","volume":"95","author":"Huang","year":"2014","journal-title":"J. Gen. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"511","DOI":"10.3201\/eid1903.120965","article-title":"Recurring influenza B virus infections in seals","volume":"19","author":"Bodewes","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12014","DOI":"10.1128\/JVI.01576-15","article-title":"RIG-I Signaling Is Essential for Influenza B Virus-Induced Rapid Interferon Gene Expression","volume":"89","author":"Westenius","year":"2015","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sharabi, S., Drori, Y., Micheli, M., Friedman, N., Orzitzer, S., Bassal, R., Glatman-Freedman, A., Shohat, T., Mendelson, E., and Hindiyeh, M. (2016). Epidemiological and Virological Characterization of Influenza B Virus Infections. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161195"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"E8296","DOI":"10.1073\/pnas.1616530113","article-title":"Development of high-yield influenza B virus vaccine viruses","volume":"113","author":"Ping","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhao, L., Xia, H., Huang, J., Zheng, Y., Liu, C., Su, J., and Ping, J. (2020). Features of Nuclear Export Signals of NS2 Protein of Influenza D Virus. Viruses, 12.","DOI":"10.3390\/v12101100"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s13238-015-0193-x","article-title":"Hemagglutinin-esterase-fusion (HEF) protein of influenza C virus","volume":"7","author":"Wang","year":"2016","journal-title":"Protein Cell"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lewnard, J.A., and Cobey, S. (2018). Immune History and Influenza Vaccine Effectiveness. Vaccines, 6.","DOI":"10.3390\/vaccines6020028"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1099\/jgv.0.000989","article-title":"Implications of segment mismatch for influenza A virus evolution","volume":"99","author":"White","year":"2018","journal-title":"J. Gen. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e01164-17","DOI":"10.1128\/JVI.01164-17","article-title":"Population Diversity and Collective Interactions during Influenza Virus Infection","volume":"91","author":"Brooke","year":"2017","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2147\/IDR.S105473","article-title":"Drug resistance in influenza A virus: The epidemiology and management","volume":"10","author":"Hussain","year":"2017","journal-title":"Infect. Drug Resist."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/5584_2020_486","article-title":"Regional Activity and Spread of Influenza Viruses in Poland in the Context of Neighboring Countries in the Epidemic Season 2017-2018: An Epidemiological Review","volume":"1271","author":"Masny","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhu, A., Liu, J., Ye, C., Yu, J., Peng, Z., Feng, L., Wang, L., Qin, Y., Zheng, Y., and Li, Z. (2020). Characteristics of Seasonal Influenza Virus Activity in a Subtropical City in China, 2013\u20132019. Vaccines, 8.","DOI":"10.3390\/vaccines8010108"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.mpmed.2013.10.017","article-title":"Influenza and other emerging respiratory viruses","volume":"42","author":"Zambon","year":"2014","journal-title":"Medicine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.vaccine.2014.11.017","article-title":"Does correcting myths about the flu vaccine work? An experimental evaluation of the effects of corrective information","volume":"33","author":"Nyhan","year":"2015","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"809","DOI":"10.3389\/fimmu.2019.00809","article-title":"Response Modifiers: Tweaking the Immune Response Against Influenza A Virus","volume":"10","author":"Elbahesh","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7774\/cevr.2018.7.1.1","article-title":"Challenges of influenza A viruses in humans and animals and current animal vaccines as an effective control measure","volume":"7","author":"Yoo","year":"2018","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Meineke, R., Rimmelzwaan, G.F., and Elbahesh, H. (2019). Influenza Virus Infections and Cellular Kinases. Viruses, 11.","DOI":"10.3390\/v11020171"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"40760","DOI":"10.1038\/srep40760","article-title":"Inhibition of Influenza A Virus Infection by Fucoidan Targeting Viral Neuraminidase and Cellular EGFR Pathway","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz-Moreno, R., Mart\u00ednez-Romero, C., and Garc\u00eda-Sastre, A. (2020). Induction and Evasion of Type-I Interferon Responses during Influenza A Virus Infection. Cold Spring Harb. Perspect. Med.","DOI":"10.1101\/cshperspect.a038414"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/978-1-4614-0980-9_9","article-title":"Influenza virus entry","volume":"726","author":"Luo","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/978-1-4614-7651-1_4","article-title":"Entry of influenza virus","volume":"790","author":"Sun","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e01425-18","DOI":"10.1128\/JVI.01425-18","article-title":"Influenza A Virus M2 Protein Apical Targeting Is Required for Efficient Virus Replication","volume":"92","author":"Wohlgemuth","year":"2018","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/med.21289","article-title":"Emerging antiviral strategies to interfere with influenza virus entry","volume":"34","author":"Vanderlinden","year":"2014","journal-title":"Med. Res. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1099\/jgv.0.001305","article-title":"Biological properties of influenza A virus mutants with amino acid substitutions in the HA2 glycoprotein of the HA1\/HA2 interaction region","volume":"100","author":"Fodor","year":"2019","journal-title":"J. Gen. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Righetto, I., Milani, A., Cattoli, G., and Filippini, F. (2014). Comparative structural analysis of haemagglutinin proteins from type A influenza viruses: Conserved and variable features. BMC Bioinform., 15.","DOI":"10.1186\/s12859-014-0363-5"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s13238-010-0054-6","article-title":"Roles of the hemagglutinin of influenza A virus in viral entry and development of antiviral therapeutics and vaccines","volume":"1","author":"Jiang","year":"2010","journal-title":"Protein Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.tim.2018.05.013","article-title":"Influenza Virus","volume":"26","author":"Hutchinson","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Galloway, S.E., Reed, M.L., Russell, C.J., and Steinhauer, D.A. (2013). Influenza HA subtypes demonstrate divergent phenotypes for cleavage activation and pH of fusion: Implications for host range and adaptation. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003151"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kubiszewski-Jakubiak, S., and Worch, R. (2020). Influenza A H1 and H3 Transmembrane Domains Interact Differently with Each Other and with Surrounding Membrane Lipids. Viruses, 12.","DOI":"10.3390\/v12121461"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23746","DOI":"10.1038\/srep23746","article-title":"Targeted disruption of influenza A virus hemagglutinin in genetically modified mice reduces viral replication and improves disease outcome","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.3390\/v4071144","article-title":"Influenza virus-mediated membrane fusion: Determinants of hemagglutinin fusogenic activity and experimental approaches for assessing virus fusion","volume":"4","author":"Hamilton","year":"2012","journal-title":"Viruses"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4149\/av_2016_02_121","article-title":"The role of fusion activity of influenza A viruses in their biological properties","volume":"60","year":"2016","journal-title":"Acta Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3390\/v5010352","article-title":"Influenza A virus entry inhibitors targeting the hemagglutinin","volume":"5","author":"Yang","year":"2013","journal-title":"Viruses"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Guo, H., Rabouw, H., Slomp, A., Dai, M., van der Vegt, F., van Lent, J.W.M., McBride, R., Paulson, J.C., de Groot, R.J., and van Kuppeveld, F.J.M. (2018). Kinetic analysis of the influenza A virus HA\/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007233"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14303","DOI":"10.1021\/acs.analchem.0c03399","article-title":"Probing the Neuraminidase Activity of Influenza Virus Using a Cytolysin A Protein Nanopore","volume":"92","author":"Kwak","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6316","DOI":"10.1128\/JVI.74.14.6316-6323.2000","article-title":"Interdependence of hemagglutinin glycosylation and neuraminidase as regulators of influenza virus growth: A study by reverse genetics","volume":"74","author":"Wagner","year":"2000","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Du, W., de Vries, E., van Kuppeveld, F.J.M., Matrosovich, M., and de Haan, C.A.M. (2020). Second sialic acid-binding site of influenza A virus neuraminidase: Binding receptors for efficient release. FEBS J.","DOI":"10.1111\/febs.15668"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e43764","DOI":"10.7554\/eLife.43764","article-title":"Influenza A virus surface proteins are organized to help penetrate host mucus","volume":"8","author":"Vahey","year":"2019","journal-title":"Elife"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.4014\/jmb.1903.03053","article-title":"Structure and Function of the Influenza A Virus Non-Structural Protein 1","volume":"29","author":"Han","year":"2019","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Makau, J.N., Watanabe, K., Otaki, H., Mizuta, S., Ishikawa, T., Kamatari, Y.O., and Nishida, N. (2020). A Quinolinone Compound Inhibiting the Oligomerization of Nucleoprotein of Influenza A Virus Prevents the Selection of Escape Mutants. Viruses, 12.","DOI":"10.3390\/v12030337"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Massari, S., Desantis, J., Nizi, M.G., Cecchetti, V., and Tabarrini, O. (2020). Inhibition of Influenza Virus Polymerase by Interfering with Its Protein-Protein Interactions. ACS Infect. Dis.","DOI":"10.1021\/acsinfecdis.0c00552"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"198186","DOI":"10.1016\/j.virusres.2020.198186","article-title":"V292I mutation in PB2 polymerase induces increased effects of E627K on influenza H7N9 virus replication in cells","volume":"291","author":"Zhou","year":"2021","journal-title":"Virus Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1038\/ncomms6509","article-title":"The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication","volume":"5","author":"Song","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/nrmicro.2016.87","article-title":"Influenza virus RNA polymerase: Insights into the mechanisms of viral RNA synthesis","volume":"14","author":"Fodor","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/1743-422X-11-167","article-title":"Emerging antiviral resistant strains of influenza A and the potential therapeutic targets within the viral ribonucleoprotein (vRNP) complex","volume":"11","author":"Davis","year":"2014","journal-title":"Virol. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13567-018-0594-y","article-title":"Identification of two residues within the NS1 of H7N9 influenza A virus that critically affect the protein stability and function","volume":"49","author":"Wang","year":"2018","journal-title":"Vet. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1007\/s00894-014-2142-7","article-title":"Virtual screening of potential inhibitors from TCM for the CPSF30 binding site on the NS1A protein of influenza A virus","volume":"20","author":"Ai","year":"2014","journal-title":"J. Mol. Model."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3957","DOI":"10.1128\/JVI.80.8.3957-3965.2006","article-title":"The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target","volume":"80","author":"Twu","year":"2006","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1128\/mr.56.1.152-179.1992","article-title":"Evolution and ecology of influenza A viruses","volume":"56","author":"Webster","year":"1992","journal-title":"Microbiol. Rev."},{"key":"ref_52","first-page":"359","article-title":"Evolution and ecology of influenza A viruses","volume":"385","author":"Yoon","year":"2014","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"a038489","DOI":"10.1101\/cshperspect.a038489","article-title":"The Ecology and Evolution of Influenza Viruses","volume":"10","author":"Wille","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Lyons, D.M., and Lauring, A.S. (2018). Mutation and Epistasis in Influenza Virus Evolution. Viruses, 10.","DOI":"10.3390\/v10080407"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Jiang, D., Wang, Q., Bai, Z., Qi, H., Ma, J., Liu, W., Ding, F., and Li, J. (2020). Could Environment Affect the Mutation of H1N1 Influenza Virus?. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17093092"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.apsb.2015.07.006","article-title":"New small-molecule drug design strategies for fighting resistant influenza A","volume":"5","author":"Shen","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.coviro.2016.05.004","article-title":"Current and novel antiviral strategies for influenza infection","volume":"18","author":"Yen","year":"2016","journal-title":"Curr. Opin. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1080\/14656566.2019.1626824","article-title":"Neuraminidase inhibitors as a strategy for influenza treatment: Pros, cons and future perspectives","volume":"20","author":"Bassetti","year":"2019","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1186\/1743-422X-10-321","article-title":"Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase","volume":"10","author":"Cohen","year":"2013","journal-title":"Virol. J."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Vorobjev, Y.N. (2020). An effective molecular blocker of ion channel of M2 protein as anti-influenza a drug. J. Biomol. Struct. Dyn., 1\u201312.","DOI":"10.1080\/07391102.2020.1747550"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.tips.2011.10.004","article-title":"Emerging cellular targets for influenza antiviral agents","volume":"33","author":"Kakkola","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/s10822-019-00189-w","article-title":"AZT acts as an anti-influenza nucleotide triphosphate targeting the catalytic site of A\/PR\/8\/34\/H1N1 RNA dependent RNA polymerase","volume":"33","author":"Pagadala","year":"2019","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.antiviral.2019.05.002","article-title":"Toll-like receptor 5 agonist flagellin reduces influenza A virus replication independently of type I interferon and interleukin 22 and improves antiviral efficacy of oseltamivir","volume":"168","author":"Georgel","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1128\/JVI.01067-13","article-title":"Evolution of the influenza A virus genome during development of oseltamivir resistance in vitro","volume":"88","author":"Renzette","year":"2014","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3389\/fcimb.2016.00060","article-title":"Oseltamivir PK\/PD Modeling and Simulation to Evaluate Treatment Strategies against Influenza-Pneumococcus Coinfection","volume":"6","author":"Boianelli","year":"2016","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/jmv.25029","article-title":"Surveillance for antiviral resistance among influenza viruses circulating in Algeria during five consecutive influenza seasons (2009\u20132014)","volume":"90","author":"Derrar","year":"2018","journal-title":"J. Med. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"9559","DOI":"10.3168\/jds.2019-16268","article-title":"Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 feeding enhances humoral immune responses, which are suppressed by the antiviral neuraminidase inhibitor oseltamivir in influenza A virus-infected mice","volume":"102","author":"Takahashi","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.ejphar.2011.04.013","article-title":"CL-385319 inhibits H5N1 avian influenza A virus infection by blocking viral entry","volume":"660","author":"Liu","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1177\/2040206617691885","article-title":"Combinations of L-N(G)-monomethyl-arginine and oseltamivir against pandemic influenza A virus infections in mice","volume":"25","author":"Smee","year":"2017","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1128\/AAC.03947-14","article-title":"Synergistic effect of nitazoxanide with neuraminidase inhibitors against influenza A viruses in vitro","volume":"59","author":"Belardo","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"546","DOI":"10.3389\/fmed.2020.00546","article-title":"Therapeutic Options Against the New Coronavirus: Updated Clinical and Laboratory Evidences","volume":"7","author":"Fernandes","year":"2020","journal-title":"Front. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"111841","DOI":"10.1016\/j.ejmech.2019.111841","article-title":"Design, synthesis and biological evaluation of oseltamivir derivatives containing pyridyl group as potent inhibitors of neuraminidase for influenza A","volume":"185","author":"Wang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1007\/s12272-018-1022-6","article-title":"The inhibitory effect of sodium baicalin on oseltamivir-resistant influenza A virus via reduction of neuraminidase activity","volume":"41","author":"Jin","year":"2018","journal-title":"Arch. Pharm. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4611","DOI":"10.1073\/pnas.1818494116","article-title":"H5N8 and H7N9 packaging signals constrain HA reassortment with a seasonal H3N2 influenza A virus","volume":"116","author":"White","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e00649-19","DOI":"10.1128\/JVI.00649-19","article-title":"TMPRSS2 Is the Major Activating Protease of Influenza A Virus in Primary Human Airway Cells and Influenza B Virus in Human Type II Pneumocytes","volume":"93","author":"Limburg","year":"2019","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ye, M., Liao, Y., Wu, L., Qi, W., Choudhry, N., Liu, Y., Chen, W., Song, G., and Chen, J. (2020). An Oleanolic Acid Derivative Inhibits Hemagglutinin-Mediated Entry of Influenza A Virus. Viruses, 12.","DOI":"10.3390\/v12020225"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Scott, C., Kankanala, J., Foster, T.L., Goldhill, D.H., Bao, P., Simmons, K., Pingen, M., Bentham, M., Atkins, E., and Loundras, E. (2020). Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008716"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Manzoor, R., Igarashi, M., and Takada, A. (2017). Influenza A Virus M2 Protein: Roles from Ingress to Egress. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122649"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"104780","DOI":"10.1016\/j.antiviral.2020.104780","article-title":"Put a cork in it: Plugging the M2 viral ion channel to sink influenza","volume":"178","author":"Jalily","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3389\/fcimb.2019.00067","article-title":"Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors","volume":"9","author":"Radosevic","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.scib.2018.08.013","article-title":"Tauroursodeoxycholic acid (TUDCA) inhibits influenza A viral infection by disrupting viral proton channel M2","volume":"64","author":"Li","year":"2019","journal-title":"Sci. Bull."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6679","DOI":"10.1128\/AAC.01156-16","article-title":"Distinct Effects of T-705 (Favipiravir) and Ribavirin on Influenza Virus Replication and Viral RNA Synthesis","volume":"60","author":"Vanderlinden","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.1128\/AAC.01579-07","article-title":"Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza virus infection in mice","volume":"52","author":"Ilyushina","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Jordan, P.C., Stevens, S.K., and Deval, J. (2018). Nucleosides for the treatment of respiratory RNA virus infections. Antivir. Chem. Chemother., 26.","DOI":"10.1177\/2040206618764483"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"107512","DOI":"10.1016\/j.pharmthera.2020.107512","article-title":"Favipiravir, an anti-influenza drug against life-threatening RNA virus infections","volume":"209","author":"Shiraki","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/QCO.0000000000000410","article-title":"Antiviral treatment of severe non-influenza respiratory virus infection","volume":"30","author":"Brendish","year":"2017","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1111\/evo.13041","article-title":"An experimental evaluation of drug-induced mutational meltdown as an antiviral treatment strategy","volume":"70","author":"Bank","year":"2016","journal-title":"Evolution"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1093\/gbe\/evx138","article-title":"The Combined Effect of Oseltamivir and Favipiravir on Influenza A Virus Evolution","volume":"9","author":"Ormond","year":"2017","journal-title":"Genome Biol. Evol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Hashimoto, T., Baba, K., Inoue, K., Okane, M., Hata, S., Shishido, T., Naito, A., Wildum, S., and Omoto, S. (2020). Comprehensive assessment of amino acid substitutions in the trimeric RNA polymerase complex of influenza A virus detected in clinical trials of baloxavir marboxil. Influenza Other Respir. Viruses.","DOI":"10.22541\/au.159284818.81967184"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/S1473-3099(20)30004-9","article-title":"Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): A randomised, placebo-controlled, phase 3 trial","volume":"20","author":"Ison","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/jac\/dkaa393","article-title":"Pharmacokinetic and pharmacodynamic analysis of baloxavir marboxil, a novel cap-dependent endonuclease inhibitor, in a murine model of influenza virus infection","volume":"76","author":"Ando","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.3201\/eid2510.190607","article-title":"Susceptibility of Influenza A, B, C, and D Viruses to Baloxavir(1)","volume":"25","author":"Mishin","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.antiviral.2018.10.008","article-title":"In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit","volume":"160","author":"Noshi","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"10132","DOI":"10.1096\/fj.201902793RR","article-title":"A77 1726, the active metabolite of the anti-rheumatoid arthritis drug leflunomide, inhibits influenza A virus replication in vitro and in vivo by inhibiting the activity of Janus kinases","volume":"34","author":"Wang","year":"2020","journal-title":"FASEB J."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Rajasekaran, D., Palombo, E.A., Chia Yeo, T., Lim Siok Ley, D., Lee Tu, C., Malherbe, F., and Grollo, L. (2013). Identification of traditional medicinal plant extracts with novel anti-influenza activity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079293"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Ti, H. (2020). Phytochemical profiles and their anti-inflammatory responses against influenza from Traditional Chinese medicine or herbs. Mini-Rev. Med. Chem.","DOI":"10.2174\/1389557520666200807134921"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Li, M., Wang, Y., Jin, J., Dou, J., Guo, Q., Ke, X., Zhou, C., and Guo, M. (2020). Inhibitory Activity of Honeysuckle Extracts against Influenza A Virus In Vitro and In Vivo. Virol. Sin.","DOI":"10.1007\/s12250-020-00302-6"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Li, Z., Li, L., Zhou, H., Zeng, L., Chen, T., Chen, Q., Zhou, B., Wang, Y., Chen, Q., and Hu, P. (2017). Radix isatidis Polysaccharides Inhibit Influenza a Virus and Influenza A Virus-Induced Inflammation via Suppression of Host TLR3 Signaling In Vitro. Molecules, 22.","DOI":"10.3390\/molecules22010116"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.2174\/138161209787846775","article-title":"Antiviral role of toll-like receptor-3 agonists against seasonal and avian influenza viruses","volume":"15","author":"Wong","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"182","DOI":"10.3389\/fmicb.2020.00182","article-title":"Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors","volume":"11","author":"Li","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Wang, H.X., Zeng, M.S., Ye, Y., Liu, J.Y., and Xu, P.P. (2020). Antiviral activity of puerarin as potent inhibitor of influenza virus neuraminidase. Phytother. Res.","DOI":"10.1002\/ptr.6803"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Li, P., Du, R., Chen, Z., Wang, Y., Zhan, P., Liu, X., Kang, D., Chen, Z., Zhao, X., and Wang, L. (2020). Punicalagin is a neuraminidase inhibitor of influenza viruses. J. Med. Virol.","DOI":"10.1002\/jmv.26449"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Wang, J., Prinz, R.A., Liu, X., and Xu, X. (2020). In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2. Viruses, 12.","DOI":"10.3390\/v12101141"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"575803","DOI":"10.3389\/fphar.2020.575803","article-title":"Traditional Chinese Medicine in Treating Influenza: From Basic Science to Clinical Applications","volume":"11","author":"Xiong","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4979850","DOI":"10.1155\/2020\/4979850","article-title":"Screening for Anti-Influenza Actives of Prefractionated Traditional Chinese Medicines","volume":"2020","author":"Kang","year":"2020","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_106","first-page":"391","article-title":"Antiviral effects of an effective section of a prescription of traditional Chinese medicine on influenza virus A in vitro","volume":"32","author":"Huang","year":"2009","journal-title":"Zhong Yao Cai"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"109471","DOI":"10.1016\/j.biopha.2019.109471","article-title":"Gegen Qinlian Decoction Downregulates the TLR7 Signalling Pathway to Control Influenza A Virus Infection","volume":"121","author":"Shi","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12985-019-1131-y","article-title":"Effect of feeding Chinese herb medicine ageratum-liquid on intestinal bacterial translocations induced by H9N2 AIV in mice","volume":"16","author":"Lu","year":"2019","journal-title":"Virol. J."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Ding, Y., Zeng, L., Li, R., Chen, Q., Zhou, B., Chen, Q., Cheng, P.L., Yutao, W., Zheng, J., and Yang, Z. (2017). The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1585-7"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13020-018-0199-4","article-title":"Effects of different principles of Traditional Chinese Medicine treatment on TLR7\/NF-\u03baB signaling pathway in influenza virus infected mice","volume":"13","author":"Fu","year":"2018","journal-title":"Chin. Med."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Li, K., Chen, X., Zhong, J., Ye, H., Zhang, S., Ge, D., Wang, X., and Wu, Y. (2020). The effects of the Xijiao Dihuang decoction combined with Yinqiao powder on miRNA-mRNA profiles in mice infected with influenza a virus. BMC Complement. Med. Ther., 20.","DOI":"10.1186\/s12906-020-03074-4"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"259","DOI":"10.21307\/pjm-2018-048","article-title":"Secondary Metabolites of Actinomycetes and their Antibacterial, Antifungal and Antiviral Properties","volume":"67","author":"Guspiel","year":"2018","journal-title":"Pol. J. Microbiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"104600","DOI":"10.1016\/j.fitote.2020.104600","article-title":"Antiviral properties of extracts of Streptomyces sp. SMU 03 isolated from the feces of Elephas maximus","volume":"143","author":"Li","year":"2020","journal-title":"Fitoterapia"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12985-019-1254-1","article-title":"Antiviral activities of extremophilic actinomycetes extracts from Kazakhstan\u2019s unique ecosystems against influenza viruses and paramyxoviruses","volume":"16","author":"Berezin","year":"2019","journal-title":"Virol. J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1007\/s00253-019-10217-2","article-title":"A new abyssomicin polyketide with anti-influenza A virus activity from a marine-derived Verrucosispora sp. MS100137","volume":"104","author":"Zhang","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s13238-016-0325-y","article-title":"3-Anhydro-6-hydroxy-ophiobolin A displays high in vitro and in vivo efficacy against influenza A virus infection","volume":"7","author":"Wang","year":"2016","journal-title":"Protein Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.1016\/j.bmcl.2013.04.034","article-title":"3-Anhydro-6-hydroxy-ophiobolin A, a new sesterterpene inhibiting the growth of methicillin-resistant Staphylococcus aureus and inducing the cell death by apoptosis on K562, from the phytopathogenic fungus Bipolaris oryzae","volume":"23","author":"Wang","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/4\/810\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:20:10Z","timestamp":1760160010000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/4\/810"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,4]]},"references-count":117,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["molecules26040810"],"URL":"https:\/\/doi.org\/10.3390\/molecules26040810","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,4]]}}}