THE COVID-19 CATALYST: A CRITICAL REVIEW OF ACCELERATED DRUG REPURPOSING STRATEGIES, LESSONS LEARNED, AND FUTURE DIRECTIONS

Authors

  • PEDIREDDI SOBITHA RANI Bhaskar Pharmacy College, Bhaskar Nagar, Yenkapally (V), Moinabad (M), R.R-500075, Hyderabad, Telangana, India https://orcid.org/0000-0002-4694-8767
  • PULLA UDAYA CHANDRIKA Bhaskar Pharmacy College, Bhaskar Nagar, Yenkapally (V), Moinabad (M), R.R-500075, Hyderabad, Telangana, India https://orcid.org/0009-0001-5232-8919
  • G. SUSMITHA Bhaskar Pharmacy College, Bhaskar Nagar, Yenkapally (V), Moinabad (M), R.R-500075, Hyderabad, Telangana, India https://orcid.org/0009-0006-5818-7033
  • LAKSHMI DEVI GOTTEMUKKULA Joginpally B. R. Pharmacy College, Bhaskar Nagar, Yenkapally (V), Moinabad (M), R.R-500075, Hyderabad, Telangana, India https://orcid.org/0000-0002-8300-0465
  • MOHD ABDUL HADI Bhaskar Pharmacy College, Bhaskar Nagar, Yenkapally (V), Moinabad (M), R.R-500075, Hyderabad, Telangana, India https://orcid.org/0000-0001-5245-4213

DOI:

https://doi.org/10.22159/ijap.2026v18i3.57254

Keywords:

Algorithmic prediction, Drug repurposing, COVID-19, Omics-guided research, In silico approach, Molecular docking, Accelerated clinical development

Abstract

Objective: To examine the significant effects of the COVID-19 pandemic on medication repurposing as a swift alternative to conventional drug development, highlighting algorithmic, omics-based, and clinical translation methodologies.

Methods: The COVID-19 pandemic is discussed starting with core concepts, encompassing definitions, classification systems, regulatory perspectives, and notable historical developments. For the reverse matching of drugs to illness profiles, we looked at both advanced computational tools and omics-based methods. The paper discussed flexible clinical trial approaches and how the rules were altered during the epidemic.

Results: Drug-candidate identification was shortened from years to months thanks to AI-assisted virtual screening, which enabled the rapid examination of thousands of approved compounds. About forty promising repurposed medications started clinical trials during the first year of the pandemic. Reliable efficacy results were rapidly produced by adaptive, data-driven trials, such as RECOVERY and ACTT. Successful medications like remdesivir, dexamethasone, and baricitinib showed definite benefits in recovery and mortality despite failures like hydroxychloroquine and lopinavir/ritonavir.Toxicity prediction and target matching were further enhanced by integrated chemical and biological databases, enabling quicker and more precise go/no-go determinations.

Conclusion: AI techniques, omics data, and adaptive clinisupervision, significantly reducing drug-development timescales from years to months without compromising regulatory oversight, as demonstrated by the COVID-19 pandemic. In addition to addressing obstacles such as off-target effects, regulatory limitations, intellectual property concerns, and limited model generalizability, the study emphasizes that future advancements will depend on the increased use of real-world evidence, precision-medicine-based repurposing, and open research collaboration.

References

1. Paul SM, Mytelka DS, Dunwiddie CT, Persinger CC, Munos BH, Lindborg SR, Schacht AL. How to improve R&D productivity: The pharmaceutical industry's grand challenge. Nat Rev Drug Discov. 2010 Mar;9(3):203-214.doi: 10.1038/nrd3078. Epub 2010 Feb 19.

2. Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, Doig A, Guilliams T, Latimer J, McNamee C, Norris A, Sanseau P, Cavalla D, Pirmohamed M. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019 Jan;18(1):41–58. doi: 10.1038/nrd.2018.168.

3. The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021 Feb;384:693–704. doi: 10.1056/NEJMoa2021436.

4. Jeon S, Ko M, Lee J, Choi I, Byun SY, Park S, Shum D, Kim S. Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs. Antimicrob Agents Chemother. 2020 Jun;64(7):e00819-20.doi: 10.1128/AAC.00819-20.

5. Jeevana JB, Venkata KR. Ultraviolet spectrophotometric method development for the estimation of a new antiviral repurposing drug,favipiravir. Asian J Pharm Clin Res. 2021 May;14(7):2455–3891. doi:10.22159/ajpcr.2021.v14i7.41966.

6. Serafin MB, Bottega A, Foletto VS, da Rosa TF, Hörner A, Hörner R. Drug repositioning is an alternative for the treatment of coronavirus COVID-19. Int J Antimicrob Agents. 2020 Jun;55(6):105969. doi: 10.1016/j.ijantimicag.2020.105969.

7. Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004 Aug;3(8):673–683. doi: 10.1038/nrd1468.

8. Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov.2020;6:14. doi: 10.1038/s41421-020-0153-3.

9. Tsang JY, Tse G. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. 2020 Oct;116(10):1688–1696. doi: 10.1093/cvr/cvaa106.

10. DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016 Mar;47:20–33. doi: 10.1016/j.jhealeco.2016.01.012.

11. Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019 Apr;20(2):273–286. doi: 10.1093/biostatistics/kxx069.

12. Mak IW, Evaniew N, Ghert M. Lost in translation: animal models and clinical trials in cancer treatment. Am J Transl Res. 2014;6(2):114–118. PMID: 24578760.

13. Mullard A. COVID-19 brings drug repurposing into the spotlight. Nat Rev Drug Discov. 2020 May;19(5):299–300. doi: 10.1038/d41573-020-00016-0.

14. Vamathevan J, Clark D, Czodrowski P, Dunham I, Ferran E, Lee G, Li B, Madabhushi A, Shah P, Spitzer M, Zhao S. Applications of machine learning in drug discovery and development. Nat Rev Drug Discov. 2019 Jun;18(6):463–477. doi: 10.1038/s41573-019-0024-5.

15. Vohora D, Singh G. Drug Repurposing: Hypothesis, Discovery and Translation. Academic Press; 2020.

16. Rolain JM, Colson P, Raoult D. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. Int J Antimicrob Agents. 2007 Oct;30(4):297–308. doi: 10.1016/j.ijantimicag.2007.05.015.

17. Ferreira LG, Dos Santos RN, Oliva G, Andricopulo AD. Molecular docking and structure-based drug design strategies. Molecules. 2015 Jul;20(7):13384–13421. doi: 10.3390/molecules200713384.

18. Scherman D, Fetro C. Drug repurposing for rare diseases: knowledge-based success stories. Therapies. 2021 Apr;76(2):211–217. doi: 10.1016/j.therap.2021.01.003.

19. Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C. Sildenafil: An orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res. 1996 Jun;8(2):47–52.

20. Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999 Nov;341(21):1565–1571. doi:10.1056/NEJM199911183412102.

21. Cohen P. Protein kinases-the major drug targets of the twenty-first century. Nat Rev Drug Discov. 2002 Apr;1(4):309–315. doi:10.1038/nrd773.

22. Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, Rawling M, Savory E, Stebbing J. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020 Feb;395(10223):e30–e31.doi: 10.1016/S0140-6736(20)30304-4.

23. Corsello SM, Bittker JA, Liu Z, Gould J, McCarren P, Hirschman JE, Johnston SE, Vrcic A, Wong B, Khan M, Asiedu J, Narayan R, Mader CC, Subramanian A, Golub TR. The Drug Repurposing Hub: A next-generation drug library and information resource. Nat Med. 2017 Apr;23(4):405–408. doi:10.1038/nm.4306.

24. Messenger AG, Rundegren J. Minoxidil: mechanisms of action on hair growth. Br J Dermatol. 2004 Feb;150(2):186-194.doi: 10.1111/j.1365-2133.2004.05785.x.

25. Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, Götte M. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem. 2020 May;295(20):6785–6797. doi:10.1074/jbc.RA120.013679.

26. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016 Oct;388(10055):2023-2038.doi: 10.1016/S0140-6736(16)30173-8.

27. Bonaventura A, Vecchié A, Dagna L, Tangianu F, Abbate A, Dentali F. Colchicine for COVID-19: targeting NLRP3 inflammasome to blunt hyperinflammation. Inflamm Res. 2022 Mar;71(3):293–307. doi:10.1007/s00011-022-01540-y

28. Oprea TI, Bauman JE, Bologa CG, Buranda T, Chigaev A, Edwards BS, Jarvik JW, Gresham HD, Haynes MK, Hjelle B, Hromas R, Hudson L, Mackenzie DA, Muller CY, Reed JC, Simons BC, Smagley Y, Strouse J, Surviladze Z, Thompson DC, Ursu O, Waller A, Winter SS, Wu Y, Young SM, Phillips GK, Sklar LA. Drug repurposing from an academic perspective. Drug Discov Today TherStrateg. 2011;8(3–4):61–69.

29. Polamreddy P, Gattu N. The drug repurposing landscape from 2012 to 2020: the evolution of the drug development paradigm. Pharmaceuticals. 2022 Apr;15(4):457. doi: 10.3390/ph1504045

30. National Center for Advancing Translational Sciences (NCATS). COVID-19 OpenData Portal. https://opendata.ncats.nih.gov/covid19/

31. U.S. Food and Drug Administration (FDA). Guidance for Industry: Applications Covered by Section 505(b)(2). Silver Spring, MD: FDA; 2020.

32. European Medicines Agency (EMA). Adaptive pathways: EMA/2016/006. https://www.ema.europa.eu/en/human-regulatory/research-development/adaptive-pathways

33. Central Drugs Standard Control Organization (CDSCO). New Drugs and Clinical Trials Rules, 2019. Ministry of Health and Family Welfare, Government of India. https://cdsco.gov.in/

34. Yin Q, Fan R, Cao X, Liu Q, Jiang R, Zeng W. DeepDrug: A general graph-based deep learning framework for drug–drug interactions and drug–target interactions prediction. Quant Biol. 2023 Jan;11(3):260–274. doi:10.15302/J-QB-022-0320.

35. Herráiz-Gil S, Nygren-Jiménez E, Acosta-Alonso DN, León C, Guerrero-Aspizua S. Artificial intelligence-based methods for drug repurposing and development in cancer. Appl Sci. 2025 Mar;15(5):2798. doi: 10.3390/app15052798.

36. Mehta S, Sharma N, Jain S. Impact of COVID-19 pandemic on maternal mortality ratio in a tertiary care hospital of Rajasthan: A retrospective analysis. Asian J Pharm Clin Res. 2022 Oct;15(10):39-41. doi:10.22159/ajpcr.2022.v15i10.45535.

37. Thirugnanasambantham P, Senthil K. In vitro and omics technologies open a new avenue for deciphering withanolide metabolism in Withaniasomnifera. Int J Pharm Pharm Sci. 2016 May;8(7):17–26.

38. Pham TH, Méndez Lucio O, Chen H, Rantalainen M, Pessia A, KaskiS.DeepCE: integrating GCN and neural networks for transcriptomics-based drug repurposing. Nat Mach Intell. 2021;3(3):247–257. doi: 10.1038/s42256-020-00285-9.

39. Zhou Y, Hou Y, Shen J, Mehra R, Kallianpur A, Culver DA, Gack MU, Farha S, Zein J, Comhair S, Fiocchi C, Stappenbeck T, Chan T, Eng C, Jung JU, Jehi L, Erzurum S, Cheng F. A network medicine approach to investigation and population based validation of disease manifestations and drug repurposing for COVID 19. PLoS Biol.2020;18(11):e3000970. doi:10.1371/journal.pbio.3000970

40. Frolkis A, Knox C, Lim E, Jewison T, Law V, Hau DD, Liu P, Ly S, Guo AC, Pon A, Banco K, Wilson M, Wu P, Wishart DS. SMPDB: The Small Molecule Pathway Database. Nucleic Acids Res. 2010;38:D480–D487. doi: 10.1093/nar/gkp1002.

41. McCreary EK, Angus DC. Efficacy of Remdesivir in COVID-19. JAMA. 2020 Sep;324(11):1048–1057. doi:10.1001/jama.2020.16349

42. Wijewickrema A, Banneheke H, Pathmeswaran A, Refai FW, Kauranaratne M, Malavige N, Jeewandara C, Ekanayake M, Samaraweera D, Thambavita D, Galappatthy P. Efficacy and safety of oral ivermectin in the treatment of mild to moderate Covid-19 patients: a multi-centre double-blind randomized controlled clinical trial. BMC Infect Dis. 2024 Jul;24:719. doi:10.1186/s12879-024-09563-y

43. U.S. Food and Drug Administration (FDA). Emergency Use Authorization Explained. https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization

44. Schcolnik-Cabrera A, Juárez-López D, Duenas-Gonzalez A. Perspectives on drug repurposing. Curr Med Chem. 2021;28(11):2085–2099. doi: 10.2174/0929867327666200831141337.

45. Goossens H, Derde L, Horby P, Bonten M. The European clinical research response to optimise treatment of patients with COVID-19: lessons learned, future perspective, and recommendations. Lancet Infect Dis. 2022May;22(5):e153–e158. doi: 10.1016/S1473-3099(21)00705-2.

46. Saber-Ayad M, Hammoudeh S, Abu-Gharbieh E, Hamoudi R, Tarazi H, Al-Tel TH, Hamid Q. Current status of baricitinib as a repurposed therapy for COVID-19. Pharmaceuticals(Basel). 2021 Jul;14(7):680. doi: 10.3390/ph14070680.

47. Li R, Ma X, Song Y, Ma Y, Lin Z, Yang Y, Liu Q, Pan Y, Liu D, Lin H. DeepDR-Net: A deep learning model for drug repurposing based on LSTM and multiple networks. Brief Bioinform. 2022 Jan;23(1):bbab495.

48. Minaee S, Kalantar R, Moghaddam HA, Fazli S, Zarei N, Sadeghi H. Machine learning and deep learning techniques for drug repurposing in COVID-19. ComputBiol Med. 2023 Jan;155:106573. doi: 10.1016/j.compbiomed.2022.106573

49. Iwata H, Mizuno S, Nagasaki M, Hirayama A, Itai A, Miyano S, Goto S, Yamada T, Kanehisa M, Yamanaka S, Nakaya A, Takahashi K, Sato H, Toh H, Tateno H, Tanaka S, Okuno Y. Discovery of drug combinations for suppressing Ebola virus using an ensemble computational approach. SciTransl Med. 2011Mar;3(80):80ps16.doi: 10.1126/scitranslmed.3001371

50. Gysi DM, Valle ÍD, Zitnik M, Ameli A, Gan X, Varol O, Sanchez H, Baron RM, Ghiassian SD, Loscalzo J, Barabási A-L. Network medicine framework for identifying drug repurposing opportunities for COVID-19. Nat Commun. 2021 Jan;12(1):1–14. doi: 10.1038/s41467-020-20661-4

51. Rajan JV, Patel N, Wheeler SE, Tabatabaei S, Sneh A, Johnson C, Kumar A, Pathan N, Jarad N, Belenchia C, Siwakoti Y, Vanchiere JA, Rodriguez M, Martinez R, Kumar S. High-throughput transcriptomics and network biology identify IL-13 and mucin pathways as therapeutic targets in post-COVID airway disease. Front Pharmacol.2023;14:1141287.doi: 10.3389/fphar.2023.1141287

52. Batista AFM, Miraglia JL, Donato THR. Multitask learning outperforms transfer learning for drug repurposing. Patterns. 2022 Jul;3(7):100536. doi: 10.1016/j.patter.2022.100536

53. Kupferschmidt K, Cohen J. Race to find COVID-19 treatments accelerates. Science. 2020 Mar;367(6485):1412–1413.doi: 10.1126/science.367.6485.1412.

54. Bellera CA, Pasqualini ME, Krall P, Jaquenod de Giusti C, Duschatsky BA, Lavandera JL, Rodríguez Varela MS, Sánchez Loria F, Bruno A, Salomon CJ. A repositioning approach using a zebrafish larvae-based model to identify potential drugs targeting SARS-CoV-2 main protease. Nat Med. 2022 Apr;28(4):642–650. doi: 10.1038/s41591-022-01720-x

55. Mullard A. 2021 FDA approvals. Nat Rev Drug Discov. 2022 Jul;21(7):471–474. doi: 10.1038/d41573-022-00037-5

56. World Health Organization (WHO). R&D Blueprint for Action to Prevent Epidemics: COVID-19. https://www.who.int/blueprint/priority-diseases/key-action/COVID-19

57. Ghosh RK, Ghosh GC, Mandal A, Goswami R, Panja P, Datta S. Integrative network biology and AI-driven drug repurposing strategies reveal potential therapeutic options against SARS-CoV-2 infection. J Transl Med. 2023 May;21(1):248.

58. Shende VA. Comprehensive review of post-COVID-19 infections: A multifaceted analysis. Int J Curr Pharm Res. 2023 Oct;15(6):43-49.

59. Santos R, Ursu O, Gaulton A, Bento AP, Donadi RS, Bologa CG, Karlsson A, Al-Lazikani B, Hersey A, Oprea TI, Overington JP. A comprehensive map of molecular drug targets. Nat Rev Drug Discov. 2017 Jan;16(1):19–34. doi:10.1038/nrd.2016.230.

Published

26-02-2026

How to Cite

SOBITHA RANI, P., CHANDRIKA, P. U., SUSMITHA, G., GOTTEMUKKULA, L. D., & HADI, M. A. (2026). THE COVID-19 CATALYST: A CRITICAL REVIEW OF ACCELERATED DRUG REPURPOSING STRATEGIES, LESSONS LEARNED, AND FUTURE DIRECTIONS. International Journal of Applied Pharmaceutics, 18(3). https://doi.org/10.22159/ijap.2026v18i3.57254

Issue

Section

Review Article(s)

Similar Articles

<< < 143 144 145 146 147 > >> 

You may also start an advanced similarity search for this article.