Skip to content
2000
Volume 32, Issue 30
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

This study aimed to undertake a complete evaluation and analysis of all known data on RNA-dependent RNA polymerase (RdRp) inhibitors, concentrating on their safety, efficacy, and current improvements in the delivery of therapeutic drugs targeting RdRp of SARS-CoV-2. The work has attempted to emphasise the necessity for future research into the development of nanocarrier-based targeted drug delivery methods for RdRp inhibitors in the treatment of COVID-19. In December 2019, a novel SARS-CoV-2 strain was discovered in Wuhan, China. SARS-CoV-2 is transferable among humans and has caused a global pandemic. The rapid global outbreak of SARS-CoV-2 and numerous deaths caused because of coronavirus disease (COVID-19) prompted the World Health Organization to announce a pandemic on March 12, 2020. COVID-19 is becoming a key concern that has a significant impact on an individual’s life status. RdRp inhibitors are major pharmaceutical agents used in the treatment of COVID-19, which have various undesirable side effects, a greater risk of recurrence, lower bioavailability, as well as a lack of targeted therapy. Hence, the present article has provided a review on all known data on RdRp inhibitors, safety, and efficacy, and recent advances in the delivery of therapeutic agents targeting RdRp of SARS-CoV-2. An analysis has been done using a scientific data search engine, such as the National Center for Biotechnology Information (NCBI/PubMed), Science Direct, Google Scholar, WIPO, Lens, The information has emphasized the need for more research into the safety, efficacy, and development of nanocarrier-based targeted drug delivery systems for RdRp inhibitors in the treatment of COVID-19.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673312897240919111317
2025-06-30
2025-09-28

  • From This Site

    /content/journals/cmc/10.2174/0109298673312897240919111317
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. OmoriR. MizumotoK. ChowellG. Changes in testing rates could mask the novel coronavirus disease (COVID-19) growth rate.Growth Rate. Int. J. Infect. Dis.20209411611810.1016/j.ijid.2020.04.02132320809
     [Google Scholar]
  2. GabuttiG. d’AncheraE. SandriF. SavioM. StefanatiA. Coronavirus: Update related to the current outbreak of COVID-19.Infect. Dis. Ther.20209224125310.1007/s40121‑020‑00295‑532292686
     [Google Scholar]
  3. MaJ. Coronavirus (COVID-19): History, current knowledge and pipeline medications.Int. J. Pharm. Pharmacol.2020411910.31531/2581‑3080.1000140
     [Google Scholar]
  4. ShahrajabianM.H. SunW. ChengQ. Product of natural evolution (SARS, MERS, and SARS-CoV-2); deadly diseases, from SARS to SARS-CoV-2.Hum. Vaccin. Immunother.2021171628310.1080/21645515.2020.179736932783700
     [Google Scholar]
  5. KarimS.S.A. KarimQ.A. Omicron SARS-CoV-2 variant: A new chapter in the COVID-19 pandemic.Lancet2021398103172126212810.1016/S0140‑6736(21)02758‑634871545
     [Google Scholar]
  6. SallardE. HalloyJ. CasaneD. van HeldenJ. DecrolyÉ. Tracing the origins of SARS-COV-2 in coronavirus phylogenies.Med. Sci. (Paris)2020368-978379610.1051/medsci/202012332773024
     [Google Scholar]
  7. HuB. GuoH. ZhouP. ShiZ.L. Characteristics of SARS-CoV-2 and COVID-19.Nat. Rev. Microbiol.202119314115410.1038/s41579‑020‑00459‑733024307
     [Google Scholar]
  8. WangL. AhnM. AndersonD.E. Bats and coronaviruses in the context of COVID-19.China CDC Wkly.20213715315510.46234/ccdcw2021.04534595031
     [Google Scholar]
  9. ChenG. WuD. GuoW. CaoY. HuangD. WangH. WangT. ZhangX. ChenH. YuH. ZhangX. ZhangM. WuS. SongJ. ChenT. HanM. LiS. LuoX. ZhaoJ. NingQ. Clinical and immunological features of severe and moderate coronavirus disease 2019.J. Clin. Invest.202013052620262910.1172/JCI13724432217835
     [Google Scholar]
  10. KimS.Y. YeniovaA.Ö. Global, regional, and national incidence and mortality of COVID-19 in 237 countries and territories, January 2022: A systematic analysis for World Health Organization COVID-19 dashboard.Life Cycle 220202019e10
     [Google Scholar]
  11. AtalanA. Is the lockdown important to prevent the COVID-19 pandemic? Effects on psychology, environment and economy-perspective.Ann. Med. Surg. (Lond.)202056June384210.1016/j.amsu.2020.06.01032562476
     [Google Scholar]
  12. ParvathaneniV. GuptaV. Utilizing drug repurposing against COVID-19 - efficacy, limitations, and challenges.Life Sci.2020259July11827510.1016/j.lfs.2020.11827532818545
     [Google Scholar]
  13. SinghT.U. ParidaS. LingarajuM.C. KesavanM. KumarD. SinghR.K. Drug repurposing approach to fight COVID-19.Pharmacol. Rep.20207261479150810.1007/s43440‑020‑00155‑632889701
     [Google Scholar]
  14. DrożdżalS. RosikJ. LechowiczK. MachajF. KotfisK. GhavamiS. ŁosM.J. FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy.Drug Resist. Updat.20205310071910.1016/j.drup.2020.10071932717568
     [Google Scholar]
  15. IslamT. Comparative evaluation of authorized drugs for treating COVID-19 patients.Health Sci. Rep.2022154e671
     [Google Scholar]
  16. MohammadS. HashemianR. HosseinM. HamblinM. R. KarimM. MirzaeiH. RdRp inhibitors and COVID-19: Is molnupiravir a good option?Biomed. Pharmacother.2022146112517
     [Google Scholar]
  17. JiangY. YinW. XuH.E. RNA-dependent RNA polymerase: Structure, mechanism, and drug discovery for COVID-19.Biochem. Biophys. Res. Commun.2021538475310.1016/j.bbrc.2020.08.11632943188
     [Google Scholar]
  18. LupasR.E. COVID-19-current therapeutical approaches and future perspectives.Processes (Basel)202210116
     [Google Scholar]
  19. StatesU. Employing drug delivery strategies to create safe and effective pharmaceuticals for COVID-19.Bioeng. Transl. Med.202052e10163
     [Google Scholar]
  20. MehtaM. PrasherP. SharmaM. ShastriM.D. KhuranaN. VyasM. DurejaH. GuptaG. AnandK. SatijaS. ChellappanD.K. DuaK. Advanced drug delivery systems can assist in targeting coronavirus disease (COVID-19): A hypothesis.Med. Hypotheses2020144July11025410.1016/j.mehy.2020.11025433254559
     [Google Scholar]
  21. HoffmannM. Kleine-WeberH. SchroederS. KrügerN. HerrlerT. ErichsenS. SchiergensT.S. HerrlerG. WuN.H. NitscheA. MüllerM.A. DrostenC. PöhlmannS. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor.Cell20201812271280.e810.1016/j.cell.2020.02.05232142651
     [Google Scholar]
  22. WanY. ShangJ. GrahamR. BaricR.S. LiF. Receptor recognition by the novel coronavirus from wuhan: an analysis based on decade-long structural studies of SARS coronavirus.J. Virol.2020947e00127-2010.1128/jvi.00127‑2031996437
     [Google Scholar]
  23. SimsA.C. BaricR.S. YountB. BurkettS.E. CollinsP.L. PicklesR.J. Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia: Role of ciliated cells in viral spread in the conducting airways of the lungs.J. Virol.20057924155111552410.1128/jvi.79.24.15511‑15524.200516306622
     [Google Scholar]
  24. TanJ. LiuS. ZhuangL. ChenL. DongM. ZhangJ. XinY. Transmission and clinical characteristics of asymptomatic patients with SARS-CoV-2 infection.Future Virol.202015637338010.2217/fvl‑2020‑0087
     [Google Scholar]
  25. TangN.L.S. ChanP.K.S. WongC.K. ToK.F. WuA.K.L. SungY.M. HuiD.S.C. SungJ.J.Y. LamC.W.K. Early enhanced expression of interferon-inducible protein-10 (CXCL-10) and other chemokines predicts adverse outcome in severe acute respiratory syndrome.Clin. Chem.200551122333234010.1373/clinchem.2005.05446016195357
     [Google Scholar]
  26. FallahA. Razavi NikooH. AbbasiH. Mohammad-HasaniA. Hosseinzadeh ColagarA. KhosraviA. Features of pathobiology and clinical translation of approved treatments for Coronavirus disease 2019.Intervirology202265311913310.1159/00052023434666335
     [Google Scholar]
  27. TianL. QiangT. LiangC. RenX. JiaM. ZhangJ. LiJ. WanM. YuWenX. LiH. CaoW. LiuH. RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic.Eur. J. Med. Chem.202121311320110.1016/j.ejmech.2021.11320133524687
     [Google Scholar]
  28. SarasteJ. PrydzK. Assembly and cellular exit of coronaviruses: Hijacking an unconventional secretory pathway from the pre-golgi intermediate compartment via the golgi ribbon to the extracellular space.Cells202110312010.3390/cells1003050333652973
     [Google Scholar]
  29. V’kovskiP. KratzelA. SteinerS. StalderH. ThielV. Coronavirus biology and replication: Implications for SARS-CoV-2.Nat. Rev. Microbiol.202119315517010.1038/s41579‑020‑00468‑633116300
     [Google Scholar]
  30. MasonR.J. Pathogenesis of COVID-19 from a cell biology perspective.Eur. Respir. J.202055491110.1183/13993003.00607‑202032269085
     [Google Scholar]
  31. MosselE.C. WangJ. JeffersS. EdeenK.E. WangS. CosgroveG.P. FunkC.J. ManzerR. MiuraT.A. PearsonL.D. HolmesK.V. MasonR.J. SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells.Virology2008372112713510.1016/j.virol.2007.09.04518022664
     [Google Scholar]
  32. ZhouY. FuB. ZhengX. WangD. ZhaoC. QiY. SunR. TianZ. XuX. WeiH. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients.Natl. Sci. Rev.202076998100210.1093/nsr/nwaa04134676125
     [Google Scholar]
  33. SiddiqiH.K. MehraM.R. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal.J. Heart Lung Transplant.202039540540710.1016/j.healun.2020.03.01232362390
     [Google Scholar]
  34. RezagholizadehA. KhialiS. SarbakhshP. Entezari-MalekiT. Remdesivir for treatment of COVID-19; an updated systematic review and meta-analysis.Eur. J. Pharmacol.2021798173926
     [Google Scholar]
  35. HashemianS.M.R. FarhadiT. VelayatiA.A. A review on favipiravir: The properties, function, and usefulness to treat COVID-19.Expert Rev. Anti Infect. Ther.20211981029103710.1080/14787210.2021.186654533372567
     [Google Scholar]
  36. MaliK.R. EerikeM. RajG.M. BisoiD. PriyadarshiniR. RaviG. ChaliserryL.F. JantiS.S. Efficacy and safety of molnupiravir in COVID-19 patients: A systematic review.Ir. J. Med. Sci.202219241665167810.1007/s11845‑022‑03139‑y36087236
     [Google Scholar]
  37. MikusG. FoersterK.I. TerstegenT. VogtC. SaidA. SchulzM. HaefeliW.E. Oral drugs against COVID-19.Dtsch. Arztebl. Int.20221191526326910.3238/arztebl.m2022.015235302484
     [Google Scholar]
  38. VitielloA. FerraraF. Association and pharmacological synergism of the triple drug therapy baricitinib/remdesivir/rhACE2 for the management of COVID-19 infection.Naunyn Schmiedebergs Arch. Pharmacol.202239519910410.1007/s00210‑021‑02169‑034669002
     [Google Scholar]
  39. DouganM. NirulaA. AzizadM. MocherlaB. GottliebR.L. ChenP. HebertC. PerryR. BosciaJ. HellerB. MorrisJ. CrystalC. IgbinadolorA. HuhnG. CardonaJ. ShawaI. KumarP. AdamsA.C. Van NaardenJ. CusterK.L. DuranteM. OakleyG. SchadeA.E. HolzerT.R. EbertP.J. HiggsR.E. KallewaardN.L. SaboJ. PatelD.R. DaboraM.C. KlekotkaP. ShenL. SkovronskyD.M. Bamlanivimab plus etesevimab in mild or moderate COVID-19.N. Engl. J. Med.2021385151382139210.1056/nejmoa210268534260849
     [Google Scholar]
  40. RazonableR.R. Tulledge-ScheitelS.M. HansonS.N. ArndtR.F. SpeicherL.L. SevilleT.A. LarsenJ.J. GaneshR. O’HoroJ.C. Real-world clinical outcomes of bebtelovimab and sotrovimab treatment of high-risk persons with coronavirus disease 2019 during the omicron epoch.Open Forum Infect. Dis.2022910ofac41110.1093/ofid/ofac41136213724
     [Google Scholar]
  41. Al-ObaidiM.M. GungorA.B. KurtinS.E. MathiasA.E. TanrioverB. ZangenehT.T. The prevention of COVID-19 in high-risk patients using tixagevimab-cilgavimab (evusheld): Real-world experience at a large academic center.Am. J. Med.20231361969910.1016/j.amjmed.2022.08.01936181789
     [Google Scholar]
  42. ZhangS. LiL. ShenA. ChenY. QiZ. Rational use of tocilizumab in the treatment of novel coronavirus pneumonia.Clin. Drug Investig.202040651151810.1007/s40261‑020‑00917‑332337664
     [Google Scholar]
  43. GrangerV. FelsA. HuetT. LaplancheJ.L. LaplancheS. ChatellierG. BeaussierH. Chollet-MartinS. de ChaisemartinL. HayemG. Circulating IL-6 but not neutrophil extracellular traps levels can predict anakinra effectiveness in patients with severe COVID-19.J. Leukoc. Biol.202211261365136710.1002/JLB.4LT0122‑018RR35704508
     [Google Scholar]
  44. WallaceM. CollinsJ.P. MolineH. PlumbI.D. GodfreyM. MorganR.L. Campos-OutcaltD. OliverS.E. DoolingK. GarganoJ.W. Effectiveness of Pfizer-BioNTech COVID-19 vaccine as evidence for policy action: A rapid systematic review and meta-analysis of non-randomized studies.PLoS One20221712e027862410.1371/journal.pone.027862436473010
     [Google Scholar]
  45. WallaceM. MouliaD. BlainA.E. RickettsE.K. MinhajF.S. Link-GellesR. CurranK.G. HadlerS.C. AsifA. GodfreyM. HallE. FioreA. MeyerS. SuJ.R. WeintraubE. OsterM.E. ShimabukuroT.T. Campos-OutcaltD. MorganR.L. BellB.P. BrooksO. TalbotH.K. LeeG.M. DaleyM.F. OliverS.E. The advisory committee on immunization practices’ recommendation for use of moderna COVID-19 vaccine in adults aged ≥18 years and considerations for extended intervals for administration of primary series doses of mRNA covid-19 vaccines - united states, february 2022.MMWR Morb. Mortal. Wkly. Rep.2022711141642110.15585/mmwr.mm7111a435298454
     [Google Scholar]
  46. OliverS.E. WallaceM. SeeI. MbaeyiS. GodfreyM. HadlerS.C. JatlaouiT.C. TwentymanE. HughesM.M. RaoA.K. FioreA. SuJ.R. BroderK.R. ShimabukuroT. LaleA. ShayD.K. MarkowitzL.E. WhartonM. BellB.P. BrooksO. McNallyV. LeeG.M. TalbotH.K. DaleyM.F. Use of the janssen (johnson & johnson) covid-19 vaccine: Updated interim recommendations from the advisory committee on immunization practices - united states, december 2021.MMWR Morb. Mortal. Wkly. Rep.2022713909510.15585/mmwr.mm7103a435051137
     [Google Scholar]
  47. TwentymanE. WallaceM. RoperL.E. AndersonT.C. RubisA.B. Fleming-DutraK.E. HallE. HsuJ. RosenblumH.G. GodfreyM. ArcherW.R. MouliaD.L. DanielL. BrooksO. TalbotH.K. LeeG.M. BellB.P. DaleyM. MeyerS. OliverS.E. Interim recommendation of the advisory committee on immunization practices for use of the novavax COVID-19 vaccine in persons aged ≥18 years - united states, july 2022.MMWR Morb. Mortal. Wkly. Rep.2022713198899210.15585/mmwr.mm7131a235925807
     [Google Scholar]
  48. HagarE. Review on different COVID-19 vaccines approved for Emergency Use Listing by WHO until 11 July 2022: Characterization, pharmacological properties, mechanism of action and adverse events.Preprint202210.14293/S2199‑1006.1.SOR‑.PPOO5F5.v1
     [Google Scholar]
  49. WangY. AnirudhanV. DuR. CuiQ. RongL. RNA-dependent RNA polymerase of SARS-CoV-2 as a therapeutic target.J. Med. Virol.202193130031010.1002/jmv.2626432633831
     [Google Scholar]
  50. WuY. LiZ. ZhaoY.S. HuangY.Y. JiangM.Y. LuoH.B. Therapeutic targets and potential agents for the treatment of COVID-19.Med. Res. Rev.20214131775179710.1002/med.2177633393116
     [Google Scholar]
  51. ZhuW. ChenC.Z. GorshkovK. XuM. LoD.C. ZhengW. RNA-dependent RNA polymerase as a target for COVID-19 drug discovery.SLAS Discov.202025101141115110.1177/247255522094212332660307
     [Google Scholar]
  52. TchesnokovE.P. FengJ.Y. PorterD.P. GötteM. Mechanism of inhibition of ebola virus RNA-dependent RNA polymerase by remdesivir.Viruses201911411610.3390/v1104032630987343
     [Google Scholar]
  53. EastmanR.T. RothJ.S. BrimacombeK.R. SimeonovA. ShenM. PatnaikS. HallM.D. Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19.ACS Cent. Sci.20206567268310.1021/acscentsci.0c0048932483554
     [Google Scholar]
  54. NiliA. FarbodA. NeishabouriA. MozafarihashjinM. TavakolpourS. MahmoudiH. Remdesivir: A beacon of hope from Ebola virus disease to COVID-19.Rev. Med. Virol.202030611310.1002/rmv.213333210457
     [Google Scholar]
  55. GottliebR.L. VacaC.E. ParedesR. MeraJ. WebbB.J. PerezG. OguchiG. RyanP. NielsenB.U. BrownM. HidalgoA. SachdevaY. MittalS. OsiyemiO. SkarbinskiJ. JunejaK. HylandR.H. OsinusiA. ChenS. CamusG. AbdelghanyM. DaviesS. Behenna-RentonN. DuffF. MartyF.M. KatzM.J. GindeA.A. BrownS.M. SchifferJ.T. HillJ.A. Early remdesivir to prevent progression to severe COVID-19 in outpatients.N. Engl. J. Med.2022386430531510.1056/nejmoa211684634937145
     [Google Scholar]
  56. ShresthaD.B. BudhathokiP. SyedN.I. RawalE. RautS. KhadkaS. Remdesivir: A potential game-changer or just a myth? A systematic review and meta-analysis.Life Sci.202126411866310.1016/j.lfs.2020.11866333121991
     [Google Scholar]
  57. Mohammad ZadehN. Mashinchi AslN.S. ForouharnejadK. GhadimiK. ParsaS. MohammadiS. OmidiA. Mechanism and adverse effects of COVID-19 drugs: A basic review.Int. J. Physiol. Pathophysiol. Pharmacol.202113410210934540130
     [Google Scholar]
  58. Ghasemnejad-berenjiM. PashapourS. Favipiravir and COVID-19: A simplified summary.Drug Res (Stuttg).2021713166170
     [Google Scholar]
  59. ShirakiK. DaikokuT. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections.Pharmacol. Ther.202020910751210.1016/j.pharmthera.2020.10751232097670
     [Google Scholar]
  60. ZhaoH. ZhuQ. ZhangC. LiJ. WeiM. QinY. ChenG. WangK. YuJ. WuZ. ChenX. WangG. Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size.Biomed. Pharmacother.202113311082510.1016/j.biopha.2020.11082533378989
     [Google Scholar]
  61. JoshiS. ParkarJ. AnsariA. VoraA. TalwarD. TiwaskarM. PatilS. BarkateH. Role of favipiravir in the treatment of COVID-19.Int. J. Infect. Dis.202110250150810.1016/j.ijid.2020.10.06933130203
     [Google Scholar]
  62. UdwadiaZ.F. SinghP. BarkateH. PatilS. RangwalaS. PendseA. KadamJ. WuW. CaractaC.F. TandonM. International journal of infectious diseases ef fi cacy and safety of favipiravir, an oral RNA-Dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19 : A randomized, comparative, open-label, multicenter, phase 3 clinical trial.Int. J. Infect. Dis.2021103627110.1016/j.ijid.2020.11.14233212256
     [Google Scholar]
  63. AgrawalU. RajuR. UdwadiaZ.F. Favipiravir: A new and emerging antiviral option in COVID-19.Med. J. Armed Forces India202076437037610.1016/j.mjafi.2020.08.00432895599
     [Google Scholar]
  64. KabingerF. StillerC. SchmitzováJ. DienemannC. KokicG. HillenH.S. HöbartnerC. CramerP. Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis.Nat. Struct. Mol. Biol.202128974074610.1038/s41594‑021‑00651‑034381216
     [Google Scholar]
  65. U.S. FoodWill Molnupiravir be the First Oral Treatment for High-Risk Non- Hospitalized Patients with Mild-Moderate COVID-19?2021Available From: https://doi.org/10.1126/scitranslmed.
  66. SinghA.K. SinghA. SinghR. MisraA. Molnupiravir in COVID-19: A systematic review of literature.Diabetes Metab. Syndr.202115610232910.1016/j.dsx.2021.10232934742052
     [Google Scholar]
  67. SyedY.Y. Molnupiravir: First approval.Drugs202282445546010.1007/s40265‑022‑01684‑535184266
     [Google Scholar]
  68. VitielloA. TroianoV. La PortaR. What will be the role of molnupiravir in the treatment of COVID-19 infection?Drugs Ther. Perspect.2021371257958010.1007/s40267‑021‑00879‑234754175
     [Google Scholar]
  69. LeeC. C. HsiehC. C. KoW. C. Molnupiravir-a novel oral Anti-SARS-CoV-2 agent.Antibiotics (Basel)202110111294
     [Google Scholar]
  70. PourkarimF. Pourtaghi-AnvarianS. RezaeeH. Molnupiravir: A new candidate for COVID-19 treatment.Pharmacol. Res. Perspect.2022101e0090910.1002/prp2.90934968008
     [Google Scholar]
  71. PlanteJ.A. MitchellB.M. PlanteK.S. DebbinkK. WeaverS.C. MenacheryV.D. The variant gambit: COVID-19's next move.Cell Host Microbe202129450851510.1016/j.chom.2021.02.02033789086
     [Google Scholar]
  72. TaoK. TzouP.L. NouhinJ. GuptaR.K. de OliveiraT. Kosakovsky PondS.L. FeraD. ShaferR.W. The biological and clinical significance of emerging SARS-CoV-2 variants.Nat. Rev. Genet.2021221275777310.1038/s41576‑021‑00408‑x34535792
     [Google Scholar]
  73. HeX. HongW. PanX. LuG. WeiX. SARS-CoV-2 Omicron variant: Characteristics and prevention.MedComm20212483884510.1002/mco2.11034957469
     [Google Scholar]
  74. VasireddyD. VanaparthyR. MohanG. MalayalaS.V. AtluriP. Review of COVID-19 variants and COVID-19 vaccine efficacy: What the clinician should know?J. Clin. Med. Res.202113631732510.14740/jocmr451834267839
     [Google Scholar]
  75. TahaH.R. KeewanN. SlatiF. Al-SawalhaN.A. Remdesivir: A closer look at its effect in COVID-19 pandemic.Pharmacology20211069-1046246810.1159/00051844034515227
     [Google Scholar]
  76. PittsJ. LiJ. PerryJ.K. Du PontV. RiolaN. RodriguezL. LuX. KurhadeC. XieX. CamusG. ManhasS. MartinR. ShiP.Y. CihlarT. PorterD.P. MoH. MaiorovaE. BilelloJ.P. Remdesivir and GS-441524 retain antiviral activity against delta, omicron, and other emergent SARS-CoV-2 variants.Antimicrob. Agents Chemother.2022666e002222210.1128/aac.00222‑2235532238
     [Google Scholar]
  77. SinghP. MavlankarA. AnsariA. SharmaM. DwivediP. Interaction of surface glycoprotein of SARS-CoV-2 variants of concern with potential drug candidates: A molecular docking study.F1000 Res.20221111710.12688/f1000research.109586.1
     [Google Scholar]
  78. BojkovaD. WideraM. CiesekS. WassM.N. MichaelisM. CinatlJ.Jr. Reduced interferon antagonism but similar drug sensitivity in Omicron variant compared to Delta variant of SARS-CoV-2 isolates.Cell Res.202232331932110.1038/s41422‑022‑00619‑935064226
     [Google Scholar]
  79. BalykovaL.A. ZaslavskayaK.Y. PavelkinaV.F. PyataevN.A. SeleznevaN.M. KirichenkoN.V. IvanovaA.Y. RodomanG.V. KolontarevK.B. SkrupskyK.S. SimakinaE.N. MubarakshinaO.A. TaganovA.V. PushkarD.Y. Effectiveness and safety of favipiravir infusion in patients hospitalized with COVID-19.Farmatsiya i Farmakol.202210111312610.19163/2307‑9266‑2022‑10‑1‑113‑126
     [Google Scholar]
  80. TianL. PangZ. LiM. LouF. AnX. ZhuS. SongL. TongY. FanH. FanJ. Molnupiravir and its antiviral activity against COVID-19.Front. Immunol.202213April85549610.3389/fimmu.2022.85549635444647
     [Google Scholar]
  81. MausA. StraitL. ZhuD. Nanoparticles as delivery vehicles for antiviral therapeutic drugs.Eng. Regen.20212March314610.1016/j.engreg.2021.03.00138620592
     [Google Scholar]
  82. WangL. WangZ. CaoL. GeK. Constructive strategies for drug delivery systems in antivirus disease therapy by biosafety materials.Biosaf. Heal.20224316117010.1016/j.bsheal.2022.03.00835291339
     [Google Scholar]
  83. HeinrichM.A. MartinaB. PrakashJ. Nanomedicine strategies to target coronavirus.Nano Today20203510096110.1016/j.nantod.2020.10096132904707
     [Google Scholar]
  84. LemboD. CavalliR. Nanoparticulate delivery systems for antiviral drugs.Antivir. Chem. Chemother.2010212537010.3851/IMP168421107015
     [Google Scholar]
  85. LemboD. DonalisioM. CivraA. ArgenzianoM. CavalliR. Nanomedicine formulations for the delivery of antiviral drugs: A promising solution for the treatment of viral infections.Expert Opin. Drug Deliv.20181519311410.1080/17425247.2017.136086328749739
     [Google Scholar]
  86. SinghR. Nanoparticle-based targeted drug delivery.Exp. Mol. Pathol.201286321522310.1016/j.yexmp.2008.12.004.Nanoparticle‑based
     [Google Scholar]
  87. GelperinaS. KisichK. IsemanM.D. HeifetsL. The potential advantages of nanoparticle drug delivery systems in chemotherapy of tuberculosis.Am. J. Respir. Crit. Care Med.2005172121487149010.1164/rccm.200504‑613PP16151040
     [Google Scholar]
  88. KhanI. SaeedK. KhanI. Nanoparticles: Properties, applications and toxicities.Arab. J. Chem.201912790893110.1016/j.arabjc.2017.05.011
     [Google Scholar]
  89. SinghS. PandeyV.K. TewariR.P. AgarwalV. Nanoparticle based drug delivery system.Advantages Appl.201143177180
     [Google Scholar]
  90. GattaniV. DawreS. Development of favipiravir loaded PLGA nanoparticles entrapped in in-situ gel for treatment of covid-19 via nasal route.J. Drug Deliv. Sci. Technol.202379104082
     [Google Scholar]
  91. AlcantaraK.P. NalinratanaN. ChutiwitoonchaiN. CastilloA.L. BanlunaraW. VajraguptaO. RojsitthisakP. RojsitthisakP. Enhanced nasal deposition and anti-coronavirus effect of favipiravir-loaded mucoadhesive chitosan-alginate nanoparticles.Pharmaceutics20221412268010.3390/pharmaceutics1412268036559173
     [Google Scholar]
  92. TulbahA.S. LeeW.H. Physicochemical characteristics and in vitro toxicity/anti-SARS-CoV-2 activity of favipiravir solid lipid nanoparticles (SLNs).Pharmaceuticals (Basel)20211410105910.3390/ph1410105934681283
     [Google Scholar]
  93. ZhangX. ZhangX. XuA. YuM. XuY. XuY. WangC. YangG. SongC. WuX. LuY. Aptamer-gated mesoporous silica nanoparticles for N protein triggered release of remdesivir and treatment of novel coronavirus (2019-nCoV).Biosensors (Basel)2022121195010.3390/bios1211095036354459
     [Google Scholar]
  94. BozzutoG. MolinariA. Liposomes as nanomedical devices.Int. J. Nanomedicine20151097599910.2147/IJN.S6886125678787
     [Google Scholar]
  95. AkbarzadehA. Rezaei-sadabadyR. DavaranS. JooS.W. ZarghamiN. Liposome: Classification, preparation, and applications.Nanoscale Res. Lett.2013811029
     [Google Scholar]
  96. DaraeeH. EtemadiA. KouhiM. AlimirzaluS. AkbarzadehA. Application of liposomes in medicine and drug delivery.Artif. Cells Nanomed. Biotechnol.201644138139110.3109/21691401.2014.95363325222036
     [Google Scholar]
  97. SercombeL. VeeratiT. MoheimaniF. WuS.Y. SoodA.K. HuaS. Advances and challenges of liposome assisted drug delivery.Front. Pharmacol.20156DEC28610.3389/fphar.2015.0028626648870
     [Google Scholar]
  98. MiereF. Formulation, characterization, and advantages of using liposomes in multiple therapies.Simona Ioana Vicaș2020113112
     [Google Scholar]
  99. WoodleM.C. Controlling liposome blood clearance by surface-grafted polymers.Adv. Drug Deliv. Rev.1998321-213915210.1016/S0169‑409X(97)00136‑110837640
     [Google Scholar]
  100. YadavD. SandeepK. PandeyD. DuttaR.K. Liposomes for drug delivery.J. Biotechnol. Biomater.20170704.10.4172/2155‑952x.1000276
     [Google Scholar]
  101. FilipczakN. PanJ. YalamartyS.S.K. TorchilinV.P. Recent advancements in liposome technology.Adv. Drug Deliv. Rev.202015642210.1016/j.addr.2020.06.02232593642
     [Google Scholar]
  102. VartakR. PatilS.M. SaraswatA. PatkiM. KundaN.K. PatelK. Aerosolized nanoliposomal carrier of remdesivir: An effective alternative for COVID-19 treatment in vitro. Nanomedicine (Lond.)202116141187120210.2217/nnm‑2020‑047533982600
     [Google Scholar]
  103. LiJ. ZhangK. WuD. RenL. ChuX. QinC. HanX. HangT. XuY. YangL. YinL. Liposomal remdesivir inhalation solution for targeted lung delivery as a novel therapeutic approach for COVID-19.Asian J. Pharm. Sci.202116677278310.1016/j.ajps.2021.09.00234703490
     [Google Scholar]
  104. ShaikN.B. Formulation and evaluation of favipiravir proliposomal powder for pulmonary delivery by nebulization.Int. J. Pharm. Res. Allied Sci.2022112364410.51847/4mcfhpccxs
     [Google Scholar]
  105. AbbasiE. AvalS.F. AkbarzadehA. MilaniM. NasrabadiH.T. JooS.W. HanifehpourY. Nejati-KoshkiK. Pashaei-AslR. Dendrimers: Synthesis, applications, and properties.Nanoscale Res. Lett.20149124710.1186/1556‑276X‑9‑24724994950
     [Google Scholar]
  106. TomaliaD.A. Birth of a new macromolecular architecture: Dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry.Prog. Polym. Sci.2005303–429432410.1016/j.progpolymsci.2005.01.007
     [Google Scholar]
  107. MishraI. Dendrimer: A novel drug delivery system.J. Drug Deliv. Ther.201112707410.22270/jddt.v1i2.46
     [Google Scholar]
  108. HalevasE. MavroidiB. KokotidouC. MoschonaA. SagnouM. MitrakiA. LitsardakisG. PelecanouM. Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery.J. Drug Deliv. Sci. Technol.202275July10362510.1016/j.jddst.2022.10362535966803
     [Google Scholar]
  109. KimS. ShiY. KimJ.Y. ParkK. ChengJ.X. Overcoming the barriers in micellar drug delivery: Loading efficiency, in vivo stability, and micelle-cell interaction.Expert Opin. Drug Deliv.201071496220017660
     [Google Scholar]
  110. JhaveriA.M. TorchilinV.P. Multifunctional polymeric micelles for delivery of drugs and siRNA.Front. Pharmacol.20145April7710.3389/fphar.2014.0007724795633
     [Google Scholar]
  111. MovassaghianS. MerkelO.M. TorchilinV.P. Applications of polymer micelles for imaging and drug delivery.Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.20157569170710.1002/WNAN.133225683687
     [Google Scholar]
  112. XuL. LiY. CaiT. ZhangJ. ChuZ. ZhangX. ShenX. WangH. CaiR. ShiH. ZhuC. PanJ. Environmentally responsive multilayer films based on block copolymer micelles and natural peptides for controlled release of favipiravir.SSRN2022
     [Google Scholar]
  113. AhmedE.M. Hydrogel: Preparation, characterization, and applications: A review.J. Adv. Res.20156210512110.1016/j.jare.2013.07.00625750745
     [Google Scholar]
  114. BahramM. MohseniN. MoghtaderM. An introduction to hydrogels and some recent applications. Emerging Concepts in Analysis and Applications of HydrogelsLondonInTechOpen2016
     [Google Scholar]
  115. JacobS. NairA.B. ShahJ. SreeharshaN. GuptaS. ShinuP. Emerging role of hydrogels in drug delivery systems.Pharmaceutics. 2021133357
     [Google Scholar]
  116. LiJ. MooneyD.J. Designing hydrogels for controlled drug delivery.Nat. Rev. Mater.201611211810.1038/natrevmats.2016.7129657852
     [Google Scholar]
  117. SalawiA. KhanA. ZamanM. RiazT. IhsanH. ButtM.H. AmanW. KhanR. MajeedI. AlmoshariY. AlshamraniM. Development of statistically optimized chemically cross-linked hydrogel for the sustained-release delivery of favipiravir.Polymers (Basel)2022141211910.3390/polym1412236935745945
     [Google Scholar]
  118. XuS. KeL. ZhaoS. LiZ. XiaoY. WuY. RenJ. QiuY. Thermosensitive poly (DHSe / PEG / PPG Urethane)-based hydrogel extended remdesivir application in ophthalmic medication.Pharmaceutics202214150
     [Google Scholar]
  119. NewmanS.P. Drug delivery to the lungs: Challenges and opportunities.Ther. Deliv.20178864766110.4155/tde‑2017‑003728730933
     [Google Scholar]
  120. ShahN.D. ShahV.V. ChivateN.D. Pulmonary drug delivery: A promising approach.J. Appl. Pharm. Sci.201226333710.7324/JAPS.2012.2632
     [Google Scholar]
  121. HickeyA.J. Emerging trends in inhaled drug delivery.Adv. Drug Deliv. Rev.2020157January637010.1016/j.addr.2020.07.00632663488
     [Google Scholar]
  122. LabirisN.R. DolovichM.B. Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications.Br. J. Clin. Pharmacol.200356658859910.1046/j.1365‑2125.2003.01892.x14616418
     [Google Scholar]
  123. AlipourS. MahmoudiL. AhmadiF. Pulmonary drug delivery: An effective and convenient delivery route to combat COVID-19.Drug Deliv. Transl. Res.2022012345678910.1007/s13346‑022‑01251‑136260223
     [Google Scholar]
  124. RamseyJ.D. StewartI.E. MaddenE.A. LimC. HwangD. HeiseM.T. HickeyA.J. KabanovA.V. Nanoformulated remdesivir with extremely low content of poly(2-oxazoline)-based stabilizer for aerosol treatment of COVID-19.Macromol. Biosci.2022228e220005610.1002/mabi.20220005635526106
     [Google Scholar]
  125. SahakijpijarnS. MoonC. KolengJ.J. ChristensenD.J. Williams IiiR.O. Development of remdesivir as a dry powder for inhalation by thin film freezing.Pharmaceutics2020121112710.3390/pharmaceutics1211100233105618
     [Google Scholar]
  126. SahakijpijarnS. MoonC. WarnkenZ.N. MaierE.Y. DeVoreJ.E. ChristensenD.J. KolengJ.J. WilliamsR.O.III In vivo pharmacokinetic study of remdesivir dry powder for inhalation in hamsters.Int. J. Pharm. X2021310007310.1016/j.ijpx.2021.10007334977555
     [Google Scholar]
  127. WongS.N. WengJ. IpI. ChenR. LakerveldR. TelfordR. BlagdenN. ScowenI.J. ChowS.F. Rational development of a carrier-free dry powder inhalation formulation for respiratory viral infections via quality by design: A drug-drug cocrystal of favipiravir and theophylline.Pharmaceutics202214230010.3390/pharmaceutics1402030035214034
     [Google Scholar]
  128. PriyonoS.R. Preparation, cellular uptake, and cytotoxic evaluation of remdesivir-hydroxypropyl-ß-cyclodextrin inclusion complex.Biomed. Pharmacol. J.202215271772710.13005/bpj/2410
     [Google Scholar]
  129. PatkiM. PalekarS. ReznikS. PatelK. Self-injectable extended release formulation of remdesivir (SelfExRem): A potential formulation alternative for COVID-19 treatment.Int. J. Pharm.2021597120329
     [Google Scholar]
  130. AvinashD. GudipatiM. RamanaM.V. VadlamudiP. NadendlaR.R. Mouth dissolving tablets of favipiravir using superdisintegrants: Preparation, optimization and in-vitro evaluation.J. Pharm. Res. Int.2021336283910.9734/jpri/2021/v33i631187
     [Google Scholar]
  131. QingweiM. Remdesivir inhalation aerosol and preparation method thereof.CN Patent 1119913742020
  132. Wen AidongL. J. WangJingwen ChaoGuo ChaoZhao YiDing Remdesivir oral fast dissolving film and preparation method thereof.CN Patent 1114943492020
  133. LifangY. I. N. Jingjingl. I. Lianjier. E. N. Remdesivir liposome for atomization inhalation and preparation method of remdesivir liposome.CN Patent 1119913752020
  134. DezuM. Freeze-dried preparation of favipiravir for injection and preparation method thereof.CN Patent 1112282262020
  135. SunD. Remdesivir and remdesivir analogs, solutions, and nanoparticle, liposomal, and microparticle compositions for treating viral infections.WO Patent 20212029072021
  136. XijingC. Liquid preparation for aerosol inhalation of Remdesivir and preparation method for liquid preparation.CN Patent 1128913272021
  137. NandiI. JainA. Transmucosal dosage forms of remdesivir.IN Patent 2020110226342021
  138. YanQ.I.U. SennanX.U. JieR.E.N. Ophthalmic temperature-sensitive in-situ gel preparation containing Remdesivir as well as preparation method and application of ophthalmic temperature-sensitive in-situ gel preparation.CN Patent 1135590562021
     [Google Scholar]
  139. NandiI. Pharmaceutical lipid compositions of remdesivir.IN Patent 2020110233852021
  140. AbidH. CaiH. Pharmaceutical formulation containing remdesivir and its active metabolites for dry powder inhalation.US Patent 202103536502021
  141. AbidH. Pharmaceutical formulation containing remdesivir and its active metabolites for dry powder inhalation.WO Patent 20212365702021
  142. ShihaiG. U. Tablet of remdesivir and preparation method therefor.WO Patent 20211689302021
     [Google Scholar]
  143. UmekarD. M. J. Tatoded. A. A. Bawankulem. A. Proliposomal dry powder inhaler of remdesivir.IN Patent 2021210465072021
  144. UmrethiaM. KhuntD. Liquid oral suspension of favipiravir.IN Patent 2020210440842021
  145. MishraS.S.B. Sustained release composition of favipiravir for the treatment of covid-19.IN Patent 2021110169282021
  146. IndranilN. Transmucosal pharmaceutical compositions of antiviral drugs.WO Patent 20212405432021
  147. DavidO. Dendrimer-drug conjugate.WO Patent 20220407612022
  148. KrishnakumarA. M. SajeevC. AshokraoD. A. Oral pharmaceutical compositions of remdesivir.WO Patent 20221234332022
  149. SriramP. RamachandraJ. V. Dry powder inhalation (dpi) formulation.WO Patent 20222240302022
  150. JieH. U. JingH. U. JingsiW. ShounaG. U. PingI. U. Favipiravir solution for aerosol inhalation and preparation method thereof.CN Patent 1141594142022
  151. ErolK. ErsinY. Immediate release composition of favipiravir.WO Patent 20221150552022
  152. YildizP. A. OgulA. A. AkbalD. O. Use of active substances with antiviral, anti malarial, and/or mucolytic properties in the treatment of viral lung diseases including covid-19 by soft mist inhaler or vibration mesh technology nebulizer through inhalation route.WO Patent 20220554492022
/content/journals/cmc/10.2174/0109298673312897240919111317
Loading
Recent Advancements in the Delivery of Therapeutic Agents Targeting RNA-dependent RNA Polymerase of SARS-CoV-2
Curr. Med. Chem. 32, 6476 (2025); https://doi.org/10.2174/0109298673312897240919111317
/content/journals/cmc/10.2174/0109298673312897240919111317
/content/journals/cmc/10.2174/0109298673312897240919111317
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): COVID-19; favipiravir; molnupiravir; nanocarriers; novel drug delivery system; remdesivir; RNA-dependent RNA polymerase; SARS-CoV-2

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test