Skip to main content

Advertisement

SpringerLink
Log in

An Overview of SARS-CoV-2 Potential Targets, Inhibitors, and Computational Insights to Enrich the Promising Treatment Strategies

  • Review Article
  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

The rapid spread of the SARS-CoV-2 virus has emphasized the urgent need for effective therapies to combat COVID-19. Investigating the potential targets, inhibitors, and in silico approaches pertinent to COVID-19 are of utmost need to develop novel therapeutic agents and reprofiling of existing FDA-approved drugs. This article reviews the viral enzymes and their counter receptors involved in the entry of SARS-CoV-2 into host cells, replication of genomic RNA, and controlling the host cell physiology. In addition, the study provides an overview of the computational techniques such as docking simulations, molecular dynamics, QSAR modeling, and homology modeling that have been used to find the FDA-approved drugs and other inhibitors against SARS-CoV-2. Furthermore, a comprehensive overview of virus-based and host-based druggable targets from a structural point of view, together with the reported therapeutic compounds against SARS-CoV-2 have also been presented. The current study offers future perspectives for research in the field of network pharmacology investigating the large unexplored molecular libraries. Overall, the present in-depth review aims to expedite the process of identifying and repurposing drugs for researchers involved in the field of COVID-19 drug discovery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Roychoudhury S, Das A, Sengupta P, Dutta S, Roychoudhury S, Choudhury AP et al (2020) Viral pandemics of the last four decades: pathophysiology, health impacts and perspectives. Int J Environ Res Public Health 17:9411. https://doi.org/10.3390/ijerph17249411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kumar S, Singh R, Kumari N, Karmakar S, Behera M, Siddiqui AJ et al (2021) Current understanding of the influence of environmental factors on SARS-CoV-2 transmission, persistence, and infectivity. Environ Sci Pollut Res 28:6267–88. https://doi.org/10.1007/s11356-020-12165-1

    Article  CAS  Google Scholar 

  3. Kaye AD, Okeagu CN, Pham AD, Silva RA, Hurley JJ, Arron BL et al (2021) Economic impact of COVID-19 pandemic on healthcare facilities and systems: International perspectives. Best Pract Res Clin Anaesthesiol 35:293–306. https://doi.org/10.1016/j.bpa.2020.11.009

    Article  PubMed  Google Scholar 

  4. Sohrabi C, Mathew G, Franchi T, Kerwan A, Griffin M, Del Mundo SC et al (2021) Impact of the coronavirus (COVID-19) pandemic on scientific research and implications for clinical academic training—a review. Int J Surg 86:57–63. https://doi.org/10.1016/j.ijsu.2020.12.008

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wilder-Smith A, Gubler DJ, Weaver SC, Monath TP, Heymann DL, Scott TW (2017) Epidemic arboviral diseases: priorities for research and public health. Lancet Infect Dis 17:e101-6. https://doi.org/10.1016/S1473-3099(16)30518-7

    Article  PubMed  Google Scholar 

  6. Nicola M, Alsafi Z, Sohrabi C, Kerwan A, Al-Jabir A, Iosifidis C et al (2020) The socio-economic implications of the coronavirus pandemic (COVID-19): a review. Int J Surg 78:185–93. https://doi.org/10.1016/j.ijsu.2020.04.018

    Article  PubMed  PubMed Central  Google Scholar 

  7. Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R (2023) Features, evaluation, and treatment of coronavirus (COVID-19). StatPearls, Treasure Island

    Google Scholar 

  8. Moradian N, Ochs HD, Sedikies C, Hamblin MR, Camargo CA, Martinez JA et al (2020) The urgent need for integrated science to fight COVID-19 pandemic and beyond. J Transl Med 18:1–7. https://doi.org/10.1186/s12967-020-02364-2

    Article  CAS  Google Scholar 

  9. Rothan HA, Byrareddy SN (2020) The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 109:102433. https://doi.org/10.1016/j.jaut.2020.102433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kangabam R, Sahoo S, Ghosh A, Roy R, Silla Y, Misra N et al (2021) Next-generation computational tools and resources for coronavirus research: from detection to vaccine discovery. Comput Biol Med 128:104158. https://doi.org/10.1016/j.compbiomed.2020.104158

    Article  CAS  PubMed  Google Scholar 

  11. Chen X, Zhang R, Xing Y, Jiang B, Li B, Xu X et al (2021) The efficacy of different seed priming agents for promoting sorghum germination under salt stress. PLoS ONE 16:1–14. https://doi.org/10.1371/journal.pone.0245505

    Article  CAS  Google Scholar 

  12. Honarparvar B, Govender T, Maguire GEM, Soliman MES, Kruger HG (2014) Integrated approach to structure-based enzymatic drug design: molecular modeling, spectroscopy, and experimental bioactivity. Chem Rev 114:493–537. https://doi.org/10.1021/cr300314q

    Article  CAS  PubMed  Google Scholar 

  13. Kazan MM, Asmare MM, Mahapatra RK (2023) Identification of potential drug targets in erythrocyte invasion pathway of Plasmodium falciparum. Curr Microbiol 80:1–10. https://doi.org/10.1007/s00284-023-03282-4

    Article  CAS  Google Scholar 

  14. Lin X, Li X, Lin X (2020) A review on applications of computational methods in drug screening and design. Molecules 25:1–17. https://doi.org/10.3390/molecules25061375

    Article  CAS  Google Scholar 

  15. Parvathaneni V, Gupta V (2020) Utilizing drug repurposing against COVID-19—efficacy, limitations, and challenges. Life Sci 259:118275. https://doi.org/10.1016/j.lfs.2020.118275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sekaran K, Karthik A, Varghese RP, Sathiyarajeswaran P, Shree Devi MS, Siva R et al (2024) In silico network pharmacology study on Glycyrrhiza glabra: analyzing the immune-boosting phytochemical properties of Siddha medicinal plant against COVID-19. Elsevier, Amsterdam, pp 233–55

    Google Scholar 

  17. Cobre AF, Maia Neto M, de Melo EB, Fachi MM, Ferreira LM, Tonin FS et al (2023) Naringenin-4’-glucuronide as a new drug candidate against the COVID-19 Omicron variant: a study based on molecular docking, molecular dynamics, MM/PBSA and MM/GBSA. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2023.2229446

    Article  PubMed  Google Scholar 

  18. Franchini M, Farrugia A, Velati C, Zanetti A, Romanò L, Grazzini G et al (2020) The impact of the SARS-CoV-2 outbreak on the safety and availability of blood transfusions in Italy. Vox Sang 115:603–5. https://doi.org/10.1111/vox.12928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Vkovski P, Kratzel A, Steiner S, Stalder H, Thiel V (2021) Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol 19:155–70. https://doi.org/10.1038/s41579-020-00468-6

    Article  CAS  PubMed  Google Scholar 

  20. Jackson CB, Farzan M, Chen B, Choe H (2022) Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 23:3–20. https://doi.org/10.1038/s41580-021-00418-x

    Article  CAS  PubMed  Google Scholar 

  21. Rahman MM, Hasan M, Ahmed A (2021) Potential detrimental role of soluble ACE2 in severe COVID-19 comorbid patients. Rev Med Virol 31:1–12. https://doi.org/10.1002/rmv.2213

    Article  CAS  PubMed  Google Scholar 

  22. Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S et al (2020) Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 581:215–20. https://doi.org/10.1038/s41586-020-2180-5

    Article  CAS  PubMed  Google Scholar 

  23. Glasgow A, Glasgow J, Limonta D, Solomon P, Lui I, Zhang Y et al (2020) Engineered ACE2 receptor traps potently neutralize SARS-CoV-2. Proc Natl Acad Sci 117:28046–55. https://doi.org/10.1073/pnas.2016093117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tang T, Bidon M, Jaimes JA, Whittaker GR, Daniel S (2020) Coronavirus membrane fusion mechanism offers a potential target for antiviral development. Antiviral Res 178:104792. https://doi.org/10.1016/j.antiviral.2020.104792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhang Q, Xiang R, Huo S, Zhou Y, Jiang S, Wang Q, et al (2021) Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy. Signal Transduct Target Ther. https://doi.org/10.1038/s41392-021-00653-w

  26. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S et al (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181:271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052

    Article  PubMed  PubMed Central  Google Scholar 

  27. Saiz ML, DeDiego ML, López-García D, Corte-Iglesias V, Baragaño Raneros A, Astola I et al (2021) Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity. Clin Epigenet 13:187. https://doi.org/10.1186/s13148-021-01168-5

    Article  CAS  Google Scholar 

  28. Qi F, Qian S, Zhang S, Zhang Z (2020) Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun 526:135–40. https://doi.org/10.1016/j.bbrc.2020.03.044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Li M, Li L, Zhang Y, Wang X (2020) An investigation of the expression of 2019 novel coronavirus cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty 9(1):1–7. https://doi.org/10.1186/s40249-020-00662-x

    Article  Google Scholar 

  30. Beyerstedt S, Casaro EB, Rangel ÉB (2021) COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. Eur J Clin Microbiol Infect Dis 40:905–19. https://doi.org/10.1007/s10096-020-04138-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Takeda M (2022) Proteolytic activation of SARS-CoV-2 spike protein. Microbiol Immunol 66:15–23. https://doi.org/10.1016/j.jbc.2022.101710

    Article  CAS  PubMed  Google Scholar 

  32. Hoffmann M, Pöhlmann S (2021) How SARS-CoV-2 makes the cut. Nat Microbiol 6:828–9. https://doi.org/10.1038/s41564-021-00931-x

    Article  CAS  PubMed  Google Scholar 

  33. Peacock TP, Goldhill DH, Zhou J, Baillon L, Frise R, Swann OC et al (2021) The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat Microbiol 6:899–909. https://doi.org/10.1038/s41564-021-00908-w

    Article  CAS  PubMed  Google Scholar 

  34. Liu J, Lu F, Chen Y, Plow E, Qin J (2022) Integrin mediates cell entry of the SARS-CoV-2 virus independent of cellular receptor ACE2. J Biol Chem 298:101710. https://doi.org/10.1016/j.jbc.2022.101710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Shulla A, Heald-Sargent T, Subramanya G, Zhao J, Perlman S, Gallagher T (2011) A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J Virol 85:873–82. https://doi.org/10.1128/JVI.02062-10

    Article  CAS  PubMed  Google Scholar 

  36. Welsch S, Müller B, Kräusslich H-G (2007) More than one door—budding of enveloped viruses through cellular membranes. FEBS Lett 581:2089–97. https://doi.org/10.1016/j.febslet.2007.03.060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Machhi J, Herskovitz J, Senan AM, Dutta D, Nath B, Oleynikov MD et al (2020) The natural history, pathobiology, and clinical manifestations of SARS-CoV-2 infections. J Neuroimmune Pharmacol 15:359–86. https://doi.org/10.1007/s11481-020-09944-5

    Article  PubMed  PubMed Central  Google Scholar 

  38. Khan S, Liu J, Xue M (2020) Transmission of SARS-CoV-2, required developments in research and associated public health concerns. Front Med. https://doi.org/10.3389/fmed.2020.00310

    Article  Google Scholar 

  39. Speiser DE, Bachmann MF (2020) Covid-19: mechanisms of vaccination and immunity. Vaccines 8:1–22. https://doi.org/10.3390/vaccines8030404

    Article  CAS  Google Scholar 

  40. Farahani M, Niknam Z, Mohammadi Amirabad L, Amiri-Dashatan N, Koushki M, Nemati M et al (2022) Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets. Biomed Pharmacother 145:112420. https://doi.org/10.1016/j.biopha.2021.112420

    Article  CAS  PubMed  Google Scholar 

  41. Yadav R, Chaudhary JK, Jain N, Chaudhary PK, Khanra S, Dhamija P et al (2021) Role of structural and non-structural proteins and therapeutic targets of SARS-CoV-2 for COVID-19. Cells 10:1–16. https://doi.org/10.3390/cells10040821

    Article  CAS  Google Scholar 

  42. Satarker S, Nampoothiri M (2020) Structural proteins in severe acute respiratory syndrome coronavirus-2. Arch Med Res 51:482–91. https://doi.org/10.1016/j.arcmed.2020.05.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Pluskota-Karwatka D, Hoffmann M, Barciszewski J (2021) Reducing SARS-CoV-2 pathological protein activity with small molecules. J Pharm Anal 11:383–97. https://doi.org/10.1016/j.jpha.2021.03.012

    Article  PubMed  PubMed Central  Google Scholar 

  44. Karygianni L, Ren Z, Koo H, Thurnheer T (2020) Biofilm matrixome: extracellular components in structured microbial communities. Trends Microbiol 28:668–81. https://doi.org/10.1016/j.tim.2020.03.016

    Article  CAS  PubMed  Google Scholar 

  45. Dutour-Provenzano G, Etienne-Manneville S (2021) Intermediate filaments. Curr Biol 31:R522-9. https://doi.org/10.1016/j.cub.2021.04.011

    Article  CAS  PubMed  Google Scholar 

  46. Mouw JK, Ou G, Weaver VM (2014) Extracellular matrix assembly: a multiscale deconstruction. Nat Rev Mol Cell Biol 15:771–85. https://doi.org/10.1038/nrm3902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Newberry RW, Raines RT (2019) Secondary forces in protein folding. ACS Chem Biol 14:1677–86. https://doi.org/10.1021/acschembio.9b00339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Harrington MJ, Fratzl P (2021) Natural load-bearing protein materials. Prog Mater Sci 120:100767. https://doi.org/10.1016/j.pmatsci.2020.100767

    Article  CAS  Google Scholar 

  49. Xu Q, Torres JE, Hakim M, Babiak PM, Pal P, Battistoni CM et al (2021) Collagen- and hyaluronic acid-based hydrogels and their biomedical applications. Mater Sci Eng R Rep 146:100641. https://doi.org/10.1016/j.mser.2021.100641

    Article  PubMed  PubMed Central  Google Scholar 

  50. Gómez SA, Rojas-Valencia N, Gómez S, Egidi F, Cappelli C, Restrepo A (2021) Binding of SARS-CoV-2 to cell receptors: a tale of molecular evolution. ChemBioChem 22:724–32. https://doi.org/10.1002/cbic.202000618

    Article  CAS  PubMed  Google Scholar 

  51. Mousavizadeh L, Ghasemi S (2021) Genotype and phenotype of COVID-19: their roles in pathogenesis. J Microbiol Immunol Infect 54:159–63. https://doi.org/10.1016/j.jmii.2020.03.022

    Article  CAS  PubMed  Google Scholar 

  52. Jamir E, Sarma H, Priyadarsinee L, Kiewhuo K, Nagamani S, Sastry GN (2022) A structure-based drug repurposing approach by considering the twenty four SARS-CoV2 targets: a consensus scoring approach. 382:727. https://doi.org/10.21203/rs.3.rs-2083023/v1

  53. Mody V, Ho J, Wills S, Mawri A, Lawson L, Ebert MCCJC et al (2021) Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents. Commun Biol 4:93. https://doi.org/10.1038/s42003-020-01577-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Venkataraman S, Prasad BVLS, Selvarajan R (2018) RNA dependent RNA polymerases: insights from structure, function and evolution. Viruses 10:1–23. https://doi.org/10.3390/v10020076

    Article  CAS  Google Scholar 

  55. Zhu W, Chen CZ, Gorshkov K, Xu M, Lo DC, Zheng W (2020) RNA-dependent RNA polymerase as a target for COVID-19 drug discovery. SLAS Discov 25:1141–51. https://doi.org/10.1177/2472555220942123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Pachetti M, Marini B, Benedetti F, Giudici F, Mauro E, Storici P et al (2020) Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. J Transl Med 18:179. https://doi.org/10.1186/s12967-020-02344-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kumar P, Parveen, Raj N, Kumar M, Fakhri KU, Kumar S et al (2024) Natural products from Streptomyces spp. as potential inhibitors of the major factors (holoRdRp and nsp13) for SARS-CoV-2 replication: an in silico approach. Arch Microbiol 206:1–23. https://doi.org/10.1007/s00203-023-03820-5

    Article  CAS  Google Scholar 

  58. Polak S, Wisniowska B, Fijorek K, Glinka A, Polak M, Mendyk A (2011) The open-access dataset for insilico cardiotoxicity prediction system. Bioinformation 6:244. https://doi.org/10.6026/97320630006244

    Article  PubMed  PubMed Central  Google Scholar 

  59. Sinha A, Vaggu RG, Swain R, Patnaik S (2023) Repurposing of RAS-pathway mediated drugs for intestinal inflammation related diseases for treating SARS-CoV-2 infection. Curr Microbiol 80:1–14. https://doi.org/10.1007/s00284-023-03304-1

    Article  CAS  Google Scholar 

  60. Ng YL, Salim CK, Chu JJH (2021) Drug repurposing for COVID-19: approaches, challenges and promising candidates. Pharmacol Ther 228:107930. https://doi.org/10.1016/j.pharmthera.2021.107930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Malin JJ, Suárez I, Priesner V, Fätkenheuer G, Rybniker J (2021) Remdesivir against COVID-19 and other viral diseases. Clin Microbiol Rev 34:1–21. https://doi.org/10.1128/CMR.00162-20

    Article  Google Scholar 

  62. Keretsu S, Bhujbal SP, Cho SJ (2020) Rational approach toward COVID-19 main protease inhibitors via molecular docking, molecular dynamics simulation and free energy calculation. Sci Rep. https://doi.org/10.1038/s41598-020-74468-0

    Article  PubMed  PubMed Central  Google Scholar 

  63. Frediansyah A, Nainu F, Dhama K, Mudatsir M, Harapan H (2021) Remdesivir and its antiviral activity against COVID-19: a systematic review. Clin Epidemiol Glob Health 9:123–7. https://doi.org/10.1016/j.cegh.2020.07.011

    Article  CAS  PubMed  Google Scholar 

  64. Eastman RT, Roth JS, Brimacombe KR, Simeonov A, Shen M, Patnaik S et al (2020) Remdesivir: a review of its discovery and development leading to emergency use authorization for treatment of COVID-19. ACS Cent Sci 6:672–83. https://doi.org/10.1021/acscentsci.0c00489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tripathy S, Dassarma B, Roy S, Chabalala H, Matsabisa MG (2020) A review on possible modes of action of chloroquine/hydroxychloroquine: repurposing against SAR-CoV-2 (COVID-19) pandemic. Int J Antimicrob Agents 56:106028. https://doi.org/10.1016/j.ijantimicag.2020.106028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hashem AM, Alghamdi BS, Algaissi AA, Alshehri FS, Bukhari A, Alfaleh MA et al (2020) Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: a narrative review. Travel Med Infect Dis 35:101735. https://doi.org/10.1016/j.tmaid.2020.101735

    Article  PubMed  PubMed Central  Google Scholar 

  67. Zhu Y, Li J, Pang Z (2021) Recent insights for the emerging COVID-19: drug discovery, therapeutic options and vaccine. Asian J Pharm Sci 16:4–23. https://doi.org/10.1016/j.ajps.2020.06.001

    Article  PubMed  Google Scholar 

  68. Gorems A, Fentahun E, Demelash Z (2021) Roles of existing drug and drug targets for COVID-19 management. Metab Open 11:100103. https://doi.org/10.1016/j.metop.2021.100103

    Article  CAS  Google Scholar 

  69. Malhani AA, Enani MA, Sharif-Askari FS, Alghareeb MR, Bin-Brikan RT, AlShahrani SA et al (2021) Combination of (interferon beta-1b, lopinavir/ritonavir and ribavirin) versus favipiravir in hospitalized patients with non-critical COVID-19: a cohort study. PLoS ONE 16:1–10. https://doi.org/10.1371/journal.pone.0252984

    Article  CAS  Google Scholar 

  70. Niknam Z, Jafari A, Golchin A, Danesh Pouya F, Nemati M, Rezaei-Tavirani M et al (2022) Potential therapeutic options for COVID-19: an update on current evidence. Eur J Med Res 27:1–15. https://doi.org/10.1186/s40001-021-00626-3

    Article  CAS  Google Scholar 

  71. Malgie J, Schoones JW, Pijls BG (2021) Decreased mortality in coronavirus disease 2019 patients treated with tocilizumab: a rapid systematic review and meta-analysis of observational studies. Clin Infect Dis 72:e742-9. https://doi.org/10.1093/cid/ciaa1445

    Article  CAS  PubMed  Google Scholar 

  72. Magro G (2020) SARS-CoV-2 and COVID-19: Is interleukin-6 (IL-6) the ‘culprit lesion’ of ARDS onset? What is there besides tocilizumab? SGP130Fc. Cytokine X 2:100029. https://doi.org/10.1016/j.cytox.2020.100029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ghanbari R, Teimoori A, Sadeghi A, Mohamadkhani A, Rezasoltani S, Asadi E et al (2020) Existing antiviral options against SARS-CoV-2 replication in COVID-19 patients. Future Microbiol 15:1747–58. https://doi.org/10.2217/fmb-2020-0120

    Article  CAS  PubMed  Google Scholar 

  74. Roy V, Agrofoglio LA (2022) Nucleosides and emerging viruses: a new story. Drug Discov Today 27:1945–53. https://doi.org/10.1016/j.drudis.2022.02.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zein AFMZ, Sulistiyana CS, Raffaello WM, Wibowo A, Pranata R (2022) Sofosbuvir with daclatasvir and the outcomes of patients with COVID-19: a systematic review and meta-analysis with GRADE assessment. Postgrad Med J 98:509–14. https://doi.org/10.1136/postgradmedj-2021-140287

    Article  PubMed  Google Scholar 

  76. Jockusch S, Tao C, Li X, Chien M, Kumar S, Morozova I et al (2020) Sofosbuvir terminated RNA is more resistant to SARS-CoV-2 proofreader than RNA terminated by Remdesivir. Sci Rep 10:16577. https://doi.org/10.1038/s41598-020-73641-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Fung HB, Stone EA, Piacenti FJ (2002) Tenofovir disoproxil fumarate: a nucleotide reverse transcriptase inhibitor for the treatment of HIV infection. Clin Ther 24:1515–48. https://doi.org/10.1016/S0149-2918(02)80058-3

    Article  CAS  PubMed  Google Scholar 

  78. Parienti JJ, Prazuck T, Peyro-Saint-Paul L, Fournier A, Valentin C, Brucato S et al (2021) Effect of tenofovir disoproxil fumarate and emtricitabine on nasopharyngeal SARS-CoV-2 viral load burden amongst outpatients with COVID-19: a pilot, randomized, open-label phase 2 trial. eClinicalMedicine 38:100993. https://doi.org/10.1016/j.eclinm.2021.100993

    Article  PubMed  PubMed Central  Google Scholar 

  79. de la Torre BG, Albericio AF (2021) The pharmaceutical industry in 2021. An analysis of FDA drug approvals from the perspective of molecules. Molecules 2022(27):1075. https://doi.org/10.3390/molecules27031075

    Article  CAS  Google Scholar 

  80. Ayerdi O, Puerta T, Clavo P, Vera M, Ballesteros J, Fuentes ME et al (2020) Preventive efficacy of tenofovir/emtricitabine against severe acute respiratory syndrome coronavirus 2 among pre-exposure prophylaxis users. Open Forum Infect Dis. https://doi.org/10.1093/ofid/ofaa455

    Article  PubMed  PubMed Central  Google Scholar 

  81. Sivakumar K, Kannappan S, Vijayakumar B (2023) Docking studies on biomolecules from marine microalga skeletonema costatum against hemolysin protein of bioluminescence disease-causing Vibrio harveyi. Curr Microbiol. 80:1–16. https://doi.org/10.1007/s00284-023-03372-3

    Article  CAS  Google Scholar 

  82. Arokia Rajan MS, Thirunavukkarasu R, Joseph J, Palliyath GK, Somarathinam K, Kothandan G et al (2023) Identification of the seaweed metabolites as potential anti-tubercular agents against human pantothenate synthetase: an in silico approach. Curr Microbiol 80:1–9. https://doi.org/10.1007/s00284-023-03422-w

    Article  CAS  Google Scholar 

  83. Sadybekov AV, Katritch V (2023) Computational approaches streamlining drug discovery. Nature 616:673–85. https://doi.org/10.1038/s41586-023-05905-z

    Article  CAS  PubMed  Google Scholar 

  84. Mohamed EAR, Abdel-Rahman IM, Zaki MEA, Al-Khdhairawi A, Abdelhamid MM, Alqaisi AM et al (2023) In silico prediction of potential inhibitors for SARS-CoV-2 omicron variant using molecular docking and dynamics simulation-based drug repurposing. J Mol Model. https://doi.org/10.1007/s00894-023-05457-z

    Article  PubMed  PubMed Central  Google Scholar 

  85. Rolta R, Yadav R, Salaria D, Trivedi S, Imran M, Sourirajan A et al (2020) In silico screening of hundred phytocompounds of ten medicinal plants as potential inhibitors of nucleocapsid phosphoprotein of COVID-19: an approach to prevent virus assembly. J Biomol Struct Dyn 0:1–18. https://doi.org/10.1080/07391102.2020.1804457

    Article  CAS  Google Scholar 

  86. Muratov EN, Amaro R, Andrade CH, Brown N, Ekins S, Fourches D et al (2021) A critical overview of computational approaches employed for COVID-19 drug discovery. Chem Soc Rev 50:9121–51. https://doi.org/10.1039/d0cs01065k

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Harwansh RK (2022) In-silico bioprospecting of taraxerol as a main protease inhibitor of SARS-CoV-2 to develop therapy against COVID-19. Struct Chem. https://doi.org/10.1007/s11224-022-01943-x

    Article  PubMed  PubMed Central  Google Scholar 

  88. Borkotoky S, Banerjee M, Modi GP, Dubey VK (2021) Identification of high affinity and low molecular alternatives of boceprevir against SARS-CoV-2 main protease: a virtual screening approach. Chem Phys Lett. 770:138446. https://doi.org/10.1016/j.cplett.2021.138446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Gil C, Ginex T, Maestro I, Nozal V, Barrado-Gil L, Cuesta-Geijo MÁ et al (2020) COVID-19: drug targets and potential treatments. J Med Chem 63:12359–86. https://doi.org/10.1021/acs.jmedchem.0c00606

    Article  CAS  PubMed  Google Scholar 

  90. Teli DM, Shah MB, Chhabria MT (2021) In silico screening of natural compounds as potential inhibitors of SARS-CoV-2 main protease and spike RBD: targets for COVID-19. Front Mol Biosci. https://doi.org/10.3389/fmolb.2020.599079

    Article  PubMed  PubMed Central  Google Scholar 

  91. Freidel MR, Armen RS (2021) Mapping major SARS-CoV-2 drug targets and assessment of druggability using computational fragment screening: Identification of an allosteric small-molecule binding site on the Nsp13 helicase. PLoS ONE 16:e0246181. https://doi.org/10.1371/journal.pone.0246181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Deniz S, Uysal TK, Capasso C, Supuran CT, Ozensoy Guler O (2021) Is carbonic anhydrase inhibition useful as a complementary therapy of Covid-19 infection? J Enzyme Inhib Med Chem 36:1230–5. https://doi.org/10.1080/14756366.2021.1924165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Rogers DM, Agarwal R, Vermaas JV, Smith MD, Rajeshwar RT, Cooper C et al (2023) SARS-CoV2 billion-compound docking. Sci Data 10:1–12. https://doi.org/10.1038/s41597-023-01984-9

    Article  CAS  Google Scholar 

  94. Amin SA, Banerjee S, Ghosh K, Gayen S, Jha T (2021) Protease targeted COVID-19 drug discovery and its challenges: insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors. Bioorg Med Chem 29:115860. https://doi.org/10.1016/j.bmc.2020.115860

    Article  CAS  PubMed  Google Scholar 

  95. Romeo A, Iacovelli F, Falconi M (2020) Targeting the SARS-CoV-2 spike glycoprotein prefusion conformation: virtual screening and molecular dynamics simulations applied to the identification of potential fusion inhibitors. Virus Res 286:198068. https://doi.org/10.1016/j.virusres.2020.198068

    Article  CAS  PubMed  Google Scholar 

  96. Saurabh S, Sivakumar PM, Perumal V, Khosravi A, Sugumaran A, Prabhawathi V (2020) Molecular dynamics simulations in drug discovery and drug delivery. Springer, Cham, pp 275–301

    Google Scholar 

  97. Chang Y, Hawkins BA, Du JJ, Groundwater PW, Hibbs DE, Lai F (2022) A guide to in silico drug design. Pharmaceutics 15:49. https://doi.org/10.3390/pharmaceutics15010049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Bai Q, Li L, Liu S, Xiao S, Guo Y (2018) Drug design progress of in silico, in vitro and in vivo researches. In-vitro In-vivo In-silico J pp 16–37

  99. Edache EI, Uzairu A, Mamza PA, Shallangwa GA (2022) QSAR, homology modeling, and docking simulation on SARS-CoV-2 and Pseudomonas aeruginosa inhibitors, ADMET, and molecular dynamic simulations to find a possible oral lead candidate. J Genet Eng Biotechnol. https://doi.org/10.1186/s43141-022-00362-z

  100. Kanan T, Kanan D, Al Shardoub EJ, Durdagi S (2021) Transcription factor NF-κB as target for SARS-CoV-2 drug discovery efforts using inflammation-based QSAR screening model. J Mol Graph Model 108:107968. https://doi.org/10.1016/j.jmgm.2021.107968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Haddad Y, Adam V, Heger Z (2020) Ten quick tips for homology modeling of high-resolution protein 3D structures. PLoS Comput Biol 16:1–13. https://doi.org/10.1371/journal.pcbi.1007449

    Article  CAS  Google Scholar 

  102. Xiang R, Yu Z, Wang Y, Wang L, Huo S, Li Y, et al (2022) Recent advances in developing small-molecule inhibitors against SARS-CoV-2. Acta Pharm Sin B. https://doi.org/10.1016/j.apsb.2021.06.016

  103. Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y et al (2020) Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 582:289–93. https://doi.org/10.1038/s41586-020-2223-y

    Article  CAS  PubMed  Google Scholar 

  104. Pearce R, Zhang Y (2021) Deep learning techniques have significantly impacted protein structure prediction and protein design. Curr Opin Struct Biol 68:194–207. https://doi.org/10.1016/j.sbi.2021.01.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Chand GB, Banerjee A, Azad GK (2020) Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure. PeerJ 8:e9492. https://doi.org/10.7717/peerj.9492

    Article  PubMed  PubMed Central  Google Scholar 

  106. Zeng L, Li D, Tong W, Shi T, Ning B (2021) Biochemical features and mutations of key proteins in SARS-CoV-2 and their impacts on RNA therapeutics. Biochem Pharmacol 189:114424. https://doi.org/10.1016/j.bcp.2021.114424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Shen W, Shi Y, Dai Z, Wang A (2020) The RNA-dependent RNA polymerase NiB of potyviruses plays multifunctional, contrasting roles during viral infection. Viruses 12:77. https://doi.org/10.3390/v12010077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Sun C, Chen L, Yang J, Luo C, Zhang Y, Li J et al (2020) SARS-CoV-2 and SARS-CoV Spike-RBD structure and receptor binding comparison and potential implications on neutralizing antibody and vaccine development. bioRxiv 25:2000044. https://doi.org/10.1101/2020.02.16.951723

    Article  CAS  Google Scholar 

  109. Luan J, Jin X, Lu Y, Zhang L (2020) SARS-CoV-2 spike protein favors ACE2 from bovidae and cricetidae. J Med Virol 92:1649–56. https://doi.org/10.1002/jmv.25817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Piccoli L, Park YJ, Tortorici MA, Czudnochowski N, Walls AC, Beltramello M et al (2020) Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology. Cell 183:1024-1042.e21. https://doi.org/10.1016/j.cell.2020.09.037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Sayed AM, Khattab AR, AboulMagd AM, Hassan HM, Rateb ME, Zaid H et al (2020) Nature as a treasure trove of potential anti-SARS-CoV drug leads: a structural/mechanistic rationale. RSC Adv 10:19790–802. https://doi.org/10.1039/D0RA04199H

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Chaturvedi M, Nagre K, Yadav JP (2021) In silico approach for identification of natural compounds as potential COVID 19 main protease (Mpro) inhibitors. VirusDisease 32:325–9. https://doi.org/10.1007/s13337-021-00701-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Buonaguro L, Tagliamonte M, Tornesello ML, Buonaguro FM (2020) SARS-CoV-2 RNA polymerase as target for antiviral therapy. J Transl Med. BioMed Central 18:1–8. https://doi.org/10.1186/s12967-020-02355-3

    Article  CAS  Google Scholar 

  114. Vicenti I, Zazzi M, Saladini F (2021) SARS-CoV-2 RNA-dependent RNA polymerase as a therapeutic target for COVID-19. Expert Opin Ther Pat 31:325–37. https://doi.org/10.1080/13543776.2021.1880568

    Article  CAS  PubMed  Google Scholar 

  115. Low ZY, Zabidi NZ, Yip AJW, Puniyamurti A, Chow VTK, Lal SK (2022) SARS-CoV-2 non-structural proteins and their roles in host immune evasion. Viruses 14:1–27. https://doi.org/10.3390/v14091991

    Article  CAS  Google Scholar 

  116. Xiaojie S, Yu L, Lei Y, Guang Y, Min Q (2021) Neutralizing antibodies targeting SARS-CoV-2 spike protein. Stem Cell Res 50:102125. https://doi.org/10.1016/j.scr.2020.102125

    Article  CAS  Google Scholar 

  117. Zeng W, Liu G, Ma H, Zhao D, Yang Y, Liu M et al (2020) Biochemical characterization of SARS-CoV-2 nucleocapsid protein. Biochem Biophys Res Commun 527:618–23. https://doi.org/10.1016/j.bbrc.2020.04.136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Narayanan K, Huang C, Lokugamage K, Kamitani W, Ikegami T, Tseng CTK et al (2008) Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells. J Virol 82:4471–9. https://doi.org/10.1128/JVI.02472-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Hagemeijer MC, Verheije MH, Ulasli M, Shaltiël IA, de Vries LA, Reggiori F et al (2010) Dynamics of coronavirus replication-transcription complexes. J Virol 84:2134–49. https://doi.org/10.1128/JVI.01716-09

    Article  CAS  PubMed  Google Scholar 

  120. Angelini MM, Akhlaghpour M, Neuman BW, Buchmeier MJ (2013) Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles. MBio. https://doi.org/10.1128/mBio.00524-13

    Article  PubMed  PubMed Central  Google Scholar 

  121. Liu Y, Qin C, Rao Y, Ngo C, Feng JJ, Zhao J et al (2021) SARS-CoV-2 Nsp5 demonstrates two distinct mechanisms targeting RIG-I and MAVS to evade the innate immune response. MBio. https://doi.org/10.1128/mBio.02335-21

    Article  PubMed  PubMed Central  Google Scholar 

  122. Raj R (2021) Analysis of non-structural proteins, NSPs of SARS-CoV-2 as targets for computational drug designing. Biochem Biophys Rep 25:100847. https://doi.org/10.1016/j.bbrep.2020.100847

    Article  CAS  PubMed  Google Scholar 

  123. Bouvet M, Imbert I, Subissi L, Gluais L, Canard B, Decroly E (2012) RNA 3′-end mismatch excision by the severe acute respiratory syndrome coronavirus nonstructural protein nsp10/nsp14 exoribonuclease complex. Proc Natl Acad Sci 109:9372–7. https://doi.org/10.1073/pnas.1201130109

    Article  PubMed  PubMed Central  Google Scholar 

  124. Wang D, Chen J, Yu C, Zhu X, Xu S, Fang L et al (2019) Porcine reproductive and respiratory syndrome virus nsp11 antagonizes type I interferon signaling by targeting IRF9. J Virol. https://doi.org/10.1128/JVI.00623-19

    Article  PubMed  PubMed Central  Google Scholar 

  125. Tahir M (2021) Coronavirus genomic nsp14-ExoN, structure, role, mechanism, and potential application as a drug target. J Med Virol 93:4258–64. https://doi.org/10.1002/jmv.27009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Chang L-J, Chen T-H (2021) NSP16 2′-O-MTase in coronavirus pathogenesis: possible prevention and treatments strategies. Viruses 13:538. https://doi.org/10.3390/v13040538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Yue Y, Nabar NR, Shi C-S, Kamenyeva O, Xiao X, Hwang I-Y et al (2018) SARS-coronavirus open reading frame-3a drives multimodal necrotic cell death. Cell Death Dis 9:904https://doi.org/10.1038/s41419-018-0917-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Kopecky-Bromberg SA, Martínez-Sobrido L, Frieman M, Baric RA, Palese P (2007) Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J Virol 81:548–57https://doi.org/10.1128/JVI.01782-06

    Article  CAS  PubMed  Google Scholar 

  129. Shiraki K, Sato N, Sakai K, Matsumoto S, Kaszynski RH, Takemoto M (2022) Antiviral therapy for COVID-19: derivation of optimal strategy based on past antiviral and favipiravir experiences. Pharmacol Ther 235:108121https://doi.org/10.1016/j.pharmthera.2022.108121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Chen J, Lin S, Niu C, Xiao Q (2021) Clinical evaluation of Shufeng jiedu capsules combined with umifenovir (Arbidol) in the treatment of common-type COVID-19: a retrospective study. Expert Rev Respir Med 15:257–65https://doi.org/10.1080/17476348.2020.1822741

    Article  CAS  PubMed  Google Scholar 

  131. Shoemaker RH, Panettieri RA, Libutti SK, Hochster HS, Watts NR, Wingfield PT et al (2022) Development of an aerosol intervention for COVID-19 disease: tolerability of soluble ACE2 (APN01) administered via nebulizer. PLoS ONE 17:e0271066https://doi.org/10.1371/journal.pone.0271066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Rogosnitzky M, Okediji P, Koman I (2020) Cepharanthine: a review of the antiviral potential of a Japanese-approved alopecia drug in COVID-19. Pharmacol Rep 72:1509–16https://doi.org/10.1007/s43440-020-00132-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Vangeel L, Chiu W, De Jonghe S, Maes P, Slechten B, Raymenants J et al (2022) Remdesivir, molnupiravir and nirmatrelvir remain active against SARS-CoV-2 omicron and other variants of concern. Antiviral Res 198:105252https://doi.org/10.1016/j.antiviral.2022.105252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Zhang Z, Wang S, Tu X, Peng X, Huang Y, Wang L et al (2020) A comparative study on the time to achieve negative nucleic acid testing and hospital stays between danoprevir and lopinavir/ritonavir in the treatment of patients with COVID-19. J Med Virol 92:2631–6https://doi.org/10.1002/jmv.26141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Doi K, Ikeda M, Hayase N, Moriya K, Morimura N, Maehara H et al (2020) Nafamostat mesylate treatment in combination with favipiravir for patients critically ill with Covid-19: a case series. Crit Care 24:392https://doi.org/10.1186/s13054-020-03078-z

    Article  PubMed  PubMed Central  Google Scholar 

  136. Sarthi P, Gupta S, Biswal S, Panda SK, Ray K, Rana MK (2022) Binding mechanism and structural insights into the identified protein target of COVID-19 and importin-α with in-vitro effective drug ivermectin. J Biomol Struct Dyn 40:2217–26. https://doi.org/10.1080/07391102.2020.1839564

    Article  CAS  Google Scholar 

  137. Cao Y, Wei J, Zou L, Jiang T, Wang G, Chen L et al (2020) Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): a multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol 146:137-146.e3. https://doi.org/10.1016/j.jaci.2020.05.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Guimarães PO, Quirk D, Furtado RH, Maia LN, Saraiva JF, Antunes MO et al (2021) Tofacitinib in patients hospitalized with covid-19 pneumonia. N Engl J Med 385:406–15. https://doi.org/10.1056/NEJMoa2101643

    Article  PubMed  Google Scholar 

  139. Aman J, Duijvelaar E, Botros L, Kianzad A, Schippers JR, Smeele PJ et al (2021) Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial. Lancet Respir Med 9:957–68. https://doi.org/10.1016/S2213-2600(21)00237-X

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Lenze EJ, Mattar C, Zorumski CF, Stevens A, Schweiger J, Nicol GE et al (2020) Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19. JAMA 324:2292. https://doi.org/10.1001/jama.2020.22760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Wang Y, Jiang W, He Q, Wang C, Wang B, Zhou P et al (2020) A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia. Signal Transduct Target Ther 5:57. https://doi.org/10.1038/s41392-020-0158-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Ramakrishnan S, Nicolau DV, Langford B, Mahdi M, Jeffers H, Mwasuku C et al (2021) Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial. Lancet Respir Med 9:763–72. https://doi.org/10.1016/S2213-2600(21)00160-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Lin Y, Wu F, Xie Z, Song X, Zhu Q, Wei J et al (2020) Clinical study of artesunate in the treatment of coronavirus disease 2019. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 32:417–20. https://doi.org/10.3760/cma.j.cn121430-20200312-00412

    Article  PubMed  Google Scholar 

  144. Nakhlband A, Fakhari A, Azizi H (2021) Interferon-beta offers promising avenues to COVID-19 treatment: a systematic review and meta-analysis of clinical trial studies. Naunyn Schmiedebergs Arch Pharmacol 394:829–38. https://doi.org/10.1007/s00210-021-02061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Al-kuraishy HM, Al-Gareeb AI, Elekhnawy E, Batiha GE-S (2022) Nitazoxanide and COVID-19: a review. Mol Biol Rep. 49:11169–76. https://doi.org/10.1007/s11033-022-07822-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Singh S, Weiss A, Goodman J, Fisk M, Kulkarni S, Lu I et al (2022) Niclosamide—a promising treatment for COVID-19. Br J Pharmacol 179:3250–67. https://doi.org/10.1111/bph.15843

    Article  CAS  PubMed  Google Scholar 

  147. Ansarin K, Tolouian R, Ardalan M, Taghizadieh A, Varshochi M, Teimouri S et al (2020) Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: a randomized clinical trial. BioImpacts 10:209–15. https://doi.org/10.34172/bi.2020.27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Earhart AP, Holliday ZM, Hofmann HV, Schrum AG (2020) Consideration of dornase alfa for the treatment of severe COVID-19 acute respiratory distress syndrome. New Microbes New Infect 35:100689. https://doi.org/10.1016/j.nmni.2020.100689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Zhao H, Davies R, Ma D (2021) Potential therapeutic value of dexmedetomidine in COVID-19 patients admitted to ICU. Br J Anaesth 126:e33-5. https://doi.org/10.1016/j.bja.2020.09.031

    Article  CAS  PubMed  Google Scholar 

  150. Mahdi M, Hermán L, Réthelyi JM, Bálint BL (2022) Potential role of the antidepressants fluoxetine and fluvoxamine in the treatment of COVID-19. Int J Mol Sci 23:3812. https://doi.org/10.3390/ijms23073812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Authors LKA & KS sincerely acknowledges the Ministry of Education, Government of India, and the Ministry of Higher Education, Government of Rajasthan, for providing grant under RUSA 2.0, Research and Innovation project.

Funding

The Authors Lokesh Kumar Agarwal and Kuldeep Sharma are grateful to RUSA 2.0 of Ministry of Education (formerly known as MHRD), New Delhi, INDIA (F30(16)SPD/RUSA/2016/178 Dated on 31 March, 2020) for financial support.

Author information

Authors and Affiliations

  1. Department of Chemistry, Mohanlal Sukhadia University, Udaipur, Rajasthan, 313001, India

    Pooja Kumawat & Lokesh Kumar Agarwal

  2. Department of Botany, Mohanlal Sukhadia University, Udaipur, Rajasthan, 313001, India

    Kuldeep Sharma

Authors
  1. Pooja Kumawat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lokesh Kumar Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kuldeep Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

P.K. wrote the original draft, Data curation; K.S. reviewed the manuscript L.K.A. conceptualized, supervised, data analysis, and reviewed the manuscript.

Corresponding author

Correspondence to Lokesh Kumar Agarwal.

Ethics declarations

Competing Interests

The authors declare that they have no known competing financial and/or non-financial interests that could have appeared to influence the work reported in this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumawat, P., Agarwal, L.K. & Sharma, K. An Overview of SARS-CoV-2 Potential Targets, Inhibitors, and Computational Insights to Enrich the Promising Treatment Strategies. Curr Microbiol 81, 169 (2024). https://doi.org/10.1007/s00284-024-03671-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00284-024-03671-3

Search

Navigation