A global picture: therapeutic perspectives for COVID-19

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1. Gralinski LE, Menachery VD. Return of the coronavirus: 2019-nCoV. Viruses 12(2), 135 (2020).
  MedlineGoogle Scholar
• 2. Dhaval Shah, Vivek Chavda HT. Nasal medication conveyance framework: an approach for brain delivery from essential to cutting edge. Res. Rev. J. Med. 6(1), 14–27 (2016).
  Google Scholar
• 3. Verity R, Okell LC, Dorigatti I et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect. Dis. 20(6), 669–677 (2020).
  Medline CASGoogle Scholar
• 4. Gupta D, Sahoo AK, Singh A. Ivermectin: potential candidate for the treatment of COVID 19. Braz. J. Infect. Dis. 24(4), 369–371 (2020).
  MedlineGoogle Scholar
• 5. Wessels I, Rolles B, Rink L. The potential impact of zinc supplementation on COVID-19 pathogenesis. Front. Immunol. 11, 1712 (2020).
  Medline CASGoogle Scholar
• 6. Liu P, Jiang J-Z, Wan X-F et al. Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)? PLoS Pathog. 16(5), e1008421 (2020).
  Medline CASGoogle Scholar
• 7. Wahyuni DS. New variants of coronavirus: what you should know. SELL J. 5(1), 55 (2020).
  Google Scholar
• 8. Chavda VP, Feehan J, Apostolopoulos V. A veterinary vaccine for SARS-CoV-2: the first COVID-19 vaccine for animals. Vaccines 9(6), 631 (2021).
  CASGoogle Scholar
• 9. Zhang T, Wu Q, Zhang Z. Probable pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak. Curr. Biol. 30(7), 1346–1351 (2020).
  Medline CASGoogle Scholar
• 10. GISAID. Official hCoV-19 reference sequence and variants (2022). www.gisaid.org/references/hcov-19-reference-sequence/
  Google Scholar
• 11. Harvey WT, Carabelli AM, Jackson B et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol. 19(7), 409–424 (2021). • Describes severe acute respiratory syndrome coronavirus-2 variants.
  Medline CASGoogle Scholar
• 12. Mirtaleb MS, Mirtaleb AH, Nosrati H et al. Potential therapeutic agents to COVID-19: an update review on antiviral therapy, immunotherapy, and cell therapy. Biomed. Pharmacother. 138, 111518 (2021). • Describes potential therapeutic targets for COVID-19 management.
  Medline CASGoogle Scholar
• 13. Chavda VP, Gajjar N, Shah N, Dave DJ. Darunavir ethanolate: repurposing an anti-HIV drug in COVID-19 treatment. Eur. J. Med. Chem. Reports 3, 100013 (2021).
  Google Scholar
• 14. Zhang W, Zhao Y, Zhang F et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China. Clin. Immunol. 214, 108393 (2020).
  Medline CASGoogle Scholar
• 15. Li Q, Guan X, Wu P et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N. Engl. J. Med. 382(13), 1199–1207 (2020).
  Medline CASGoogle Scholar
• 16. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA 323(18), 1824–1836 (2020).
  Medline CASGoogle Scholar
• 17. Iqbal Yatoo M, Hamid Z, Rather I et al. Immunotherapies and immunomodulatory approaches in clinical trials – a mini review. Hum. Vaccin. Immunother. 17(7), 1–13 (2021).
  MedlineGoogle Scholar
• 18. Chavda VP, Hossain MK, Beladiya J, Apostolopoulos V. Nucleic acid vaccines for COVID-19: a paradigm shift in the vaccine development arena. Biologics 1(3), 337–356 (2021). • Details development of nucleic acid-based vaccines for COVID-19.
  Google Scholar
• 19. Chavda VP, Vora LK, Pandya AK, Patravale VB. Intranasal vaccines for SARS-CoV-2: from challenges to potential in COVID-19 management. Drug Discov. Today 26(11), 2619–2636 (2021).
  Medline CASGoogle Scholar
• 20. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat. Med. 26(4), 450–452 (2020).
  Medline CASGoogle Scholar
• 21. Pal M, Berhanu G, Desalegn C, Kandi V. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): an update. Cureus 12(3), e7423 (2020).
  MedlineGoogle Scholar
• 22. Aronson JK. The Centre for Evidence-Based Medicine. Coronaviruses – a general introduction. (2020). http://www.cebm.net/covid-19/coronaviruses-a-general-introduction/
  Google Scholar
• 23. Ciotti M, Ciccozzi M, Terrinoni A et al. The COVID-19 pandemic. Crit. Rev. Clin. Lab. Sci. 57(6), 1–24 (2020).
  MedlineGoogle Scholar
• 24. Tao K, Tzou PL, Nouhin J et al. The biological and clinical significance of emerging SARS-CoV-2 variants. Nat. Rev. Genet. 22(12), 757–773 (2021).
  Medline CASGoogle Scholar
• 25. Gao Y-M, Xu G, Wang B, Liu B-C. Cytokine storm syndrome in coronavirus disease 2019: a narrative review. J. Intern. Med. 289(2), 147–161 (2021).
  Medline CASGoogle Scholar
• 26. Abdool Karim SS, de Oliveira T. New SARS-CoV-2 variants – clinical, public health, and vaccine implications. N. Engl. J. Med. 384(19), 1866–1868 (2021).
  MedlineGoogle Scholar
• 27. Lauring AS, Hodcroft EB. Genetic variants of SARS-CoV-2 - what do they mean? JAMA 325(6), 529–531 (2021).
  Medline CASGoogle Scholar
• 28. NCIRD. CDC. Omicron variant: what you need to know (2021). www.cdc.gov/coronavirus/2019-ncov/variants/omicron-variant.html
  Google Scholar
• 29. Callaway E. Heavily mutated Omicron variant puts scientists on alert. Nature 600(7887), 21 (2021).
  Medline CASGoogle Scholar
• 30. Li F. Structure, function, and evolution of coronavirus spike proteins. Annu. Rev. Virol. 3, 237–261 (2016).
  Medline CASGoogle Scholar
• 31. Huang Y, Yang C, Xu X, Xu W, Liu S. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol. Sin. 41(9), 1141–1149 (2020).
  MedlineGoogle Scholar
• 32. Xia S, Zhu Y, Liu M et al. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell. Mol. Immunol. 17(7), 765–767 (2020).
  Medline CASGoogle Scholar
• 33. V'kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat. Rev. Microbiol. 19(3), 155–170 (2021). • Describes severe acute respiratory syndrome coronavirus-2 replication process.
  MedlineGoogle Scholar
• 34. Wu Y, Li Z, Zhao Y et al. Therapeutic targets and potential agents for the treatment of COVID-19. Med. Res. Rev. 41(3), 1775–1797 (2021).
  Medline CASGoogle Scholar
• 35. Zhang Q, Xiang R, Huo S et al. Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy. Signal Transduct. Target. Ther. 6(1), 233 (2021).
  Medline CASGoogle Scholar
• 36. Hoffmann M, Kleine-Weber H, Schroeder S et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181(2), 271–280.e8 (2020).
  Medline CASGoogle Scholar
• 37. Ou X, Liu Y, Lei X et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat. Commun. 11(1), 1620 (2020).
  Medline CASGoogle Scholar
• 38. Mortaz E, Tabarsi P, Varahram M, Folkerts G, Adcock IM. The immune response and immunopathology of COVID-19. Front. Immunol. 11, 1–9 (2020).
  MedlineGoogle Scholar
• 39. Mousavizadeh L, Ghasemi S. Genotype and phenotype of COVID-19: their roles in pathogenesis. J. Microbiol. Immunol. Infect. 54(2), 159–163 (2021).
  Medline CASGoogle Scholar
• 40. Astuti I, Ysrafil Y. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): an overview of viral structure and host response. Diabetes Metab. Syndr. 14(4), 407–412 (2020).
  MedlineGoogle Scholar
• 41. Wang C, Wang Z, Wang G et al. COVID-19 in early 2021: current status and looking forward. Signal Transduct. Target. Ther. 6(1), 114 (2021). • Describes severe acute respiratory syndrome coronavirus 2 pathophysiology.
  Medline CASGoogle Scholar
• 42. Singh TU, Parida S, Lingaraju MC et al. Drug repurposing approach to fight COVID-19. Pharmacol. Rep. 72(6), 1479–1508 (2020).
  Medline CASGoogle Scholar
• 43. Shrestha DB, Budhathoki P, Khadka S et al. Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and meta-analysis. Virol. J. 17(1), 141 (2020).
  Medline CASGoogle Scholar
• 44. Feuillet V, Canard B, Trautmann A. Combining antivirals and immunomodulators to fight COVID-19. Trends Immunol. 42(1), 31–44 (2021).
  Medline CASGoogle Scholar
• 45. Ardestani A, Azizi Z. Targeting glucose metabolism for treatment of COVID-19. Signal Transduct. Target. Ther. 6(1), 112 (2021).
  Medline CASGoogle Scholar
• 46. Pajak B, Siwiak E, Sołtyka M et al. 2-Deoxy-D-glucose and its analogs: from diagnostic to therapeutic agents. Int. J. Mol. Sci. 21(1), 234 (2019).
  Google Scholar
• 47. Mantha M, Suvvari T, Corriero A. 2-Deoxy-D-glucose as an armament against COVID-19: the key to return to normality? Biomed. Biotechnol. Res. J. 5(3), 347–348 (2021).
  Google Scholar
• 48. Kifle ZD, Ayele AG, Enyew EF. Drug repurposing approach, potential drugs, and novel drug targets for COVID-19 treatment. J. Environ. Public Health 2021, 6631721 (2021).
  MedlineGoogle Scholar
• 49. Zhou Y, Hou Y, Shen J et al. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 6, 14 (2020).
  Medline CASGoogle Scholar
• 50. Li X, Yu J, Zhang Z et al. Network bioinformatics analysis provides insight into drug repurposing for COVID-19. Med. Drug Discov. 10, 100090 (2021).
  Medline CASGoogle Scholar
• 51. Balmeh N, Mahmoudi S, Mohammadi N, Karabedianhajiabadi A. Predicted therapeutic targets for COVID-19 disease by inhibiting SARS-CoV-2 and its related receptors. Informatics Med. Unlocked 20, 100407 (2020).
  MedlineGoogle Scholar
• 52. Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol. Sin. 41(9), 1141–1149 (2020).
  MedlineGoogle Scholar
• 53. Karoyan P, Vieillard V, Gómez-Morales L et al. Human ACE2 peptide-mimics block SARS-CoV-2 pulmonary cells infection. Commun. Biol. 4(1), 197 (2021).
  Medline CASGoogle Scholar
• 54. Rahbar Saadat Y, Hosseiniyan Khatibi SM, Zununi Vahed S, Ardalan M. Host serine proteases: a potential targeted therapy for COVID-19 and influenza. Front. Mol. Biosci. 8, 816 (2021).
  Google Scholar
• 55. Padhi AK, Seal A, Khan JM, Ahamed M, Tripathi T. Unraveling the mechanism of arbidol binding and inhibition of SARS-CoV-2: insights from atomistic simulations. Eur. J. Pharmacol. 894, 173836 (2021).
  Medline CASGoogle Scholar
• 56. Vankadari N. Arbidol: a potential antiviral drug for the treatment of SARS-CoV-2 by blocking trimerization of the spike glycoprotein. Int. J. Antimicrob. Agents 56(2), 105998 (2020).
  Medline CASGoogle Scholar
• 57. Saxena A. Drug targets for COVID-19 therapeutics: ongoing global efforts. J. Biosci. 45(1), 87 (2020).
  Medline CASGoogle Scholar
• 58. Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J. Crit. Care 57, 279–283 (2020).
  Medline CASGoogle Scholar
• 59. Wondmkun YT, Mohammed OA. A review on novel drug targets and future directions for COVID-19 treatment. Biol. Targets Ther. 14, 77–82 (2020).
  CASGoogle Scholar
• 60. McClain CB, Vabret N. SARS-CoV-2: the many pros of targeting PLpro. Signal Transduct. Target. Ther. 5(1), 1–8 (2020).
  MedlineGoogle Scholar
• 61. Alexpandi R, De Mesquita JF, Pandian SK, Ravi AV. Quinolines-based SARS-CoV-2 3CLpro and RdRp inhibitors and spike-RBD-ACE2 inhibitor for drug-repurposing against COVID-19: an in silico analysis. Front. Microbiol. 11, 1–21 (2020).
  MedlineGoogle Scholar
• 62. Nur SM, Hasan MA, Al Amin M, Hossain M, Sharmin T. Design of potential RNAi (miRNA and siRNA) molecules for Middle East respiratory syndrome coronavirus (MERS-CoV) gene silencing by computational method. Interdiscip. Sci. Comput. Life Sci. 7(3), 257–265 (2015).
  Medline CASGoogle Scholar
• 63. Mélo Silva Júnior ML, Souza LMA, Dutra REMC, Valente RGM, Melo TS. Review on therapeutic targets for COVID-19: insights from cytokine storm. Postgrad. Med. J. 97(1148), 391–398 (2020).
  MedlineGoogle Scholar
• 64. Hashizume M. Outlook of IL-6 signaling blockade for COVID-19 pneumonia. Inflamm. Regen. 40(1), 1–34 (2020).
  MedlineGoogle Scholar
• 65. Stebbing J, Phelan A, Griffin I et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect. Dis. 20(4), 400–402 (2020).
  Medline CASGoogle Scholar
• 66. Muthaiyan M, Pushan SS, Naorem LD, Venkatesan A. Understanding of Zaire ebolavirus–human protein interaction for drug repurposing. Virusdisease 31(1), 28–37 (2020).
  MedlineGoogle Scholar
• 67. Dyall J, Coleman CM, Hart BJ et al. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob. Agents Chemother. 58(8), 4885–4893 (2014).
  MedlineGoogle Scholar
• 68. Mirza MU, Froeyen M. Structural elucidation of SARS-CoV-2 vital proteins: computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase. J. Pharm. Anal. 10(4), 320–328 (2020).
  MedlineGoogle Scholar
• 69. Karaman B, Sippl W. Computational drug repurposing: current trends. Curr. Med. Chem. 26(28), 5389–5409 (2019).
  Medline CASGoogle Scholar
• 70. Hasan A, Paray BA, Hussain A et al. A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin. J. Biomol. Struct. Dyn. 39(8), 3025–3033 (2021).
  Medline CASGoogle Scholar
• 71. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin. Immunopathol. 39(5), 529–539 (2017).
  Medline CASGoogle Scholar
• 72. Schoergenhofer C, Jilma B, Stimpfl T, Karolyi M, Zoufaly A. Pharmacokinetics of lopinavir and ritonavir in patients hospitalized with coronavirus disease 2019 (COVID-19). Ann. Intern. Med. 173(8), 670–672 (2020).
  MedlineGoogle Scholar
• 73. Nabirotchkin S, Peluffo AE, Rinaudo P et al. Next-generation drug repurposing using human genetics and network biology. Curr. Opin. Pharmacol. 51, 78–92 (2020).
  Medline CASGoogle Scholar
• 74. Trosset J-Y, Cavé C. In silico drug-target profiling. Methods Mol. Biol. 1953, 89–103 (2019).
  Medline CASGoogle Scholar
• 75. Wang MY, Zhao R, Gao LJ, Gao XF, Wang DP, Cao JM. SARS-CoV-2: structure, biology, and structure-based therapeutics development. Front. Cell. Infect. Microbiol. 10, 1–17 (2020).
  MedlineGoogle Scholar
• 76. Kim H. Outbreak of novel coronavirus (COVID-19): what is the role of radiologists? Eur. Radiol. 30(6), 3266–3267 (2020).
  Medline CASGoogle Scholar
• 77. Majumder J, Minko T. Recent developments on therapeutic and diagnostic approaches for COVID-19. AAPS J. 23(1), 14 (2021).
  Medline CASGoogle Scholar
• 78. Parasher A. COVID-19: current understanding of its pathophysiology, clinical presentation and treatment. Postgrad. Med. J. 97(1147), 312–320 (2021).
  MedlineGoogle Scholar
• 79. Tarighi P, Eftekhari S, Chizari M et al. A review of potential suggested drugs for coronavirus disease (COVID-19) treatment. Eur. J. Pharmacol. 895, 173890 (2021). • Drug repurposing for COVID-19 management.
  Medline CASGoogle Scholar
• 80. Majumder J, Minko T. Recent developments on therapeutic and diagnostic approaches for COVID-19. AAPS J. 23(1), 14 (2021).
  Medline CASGoogle Scholar
• 81. Chibber P, Haq SA, Ahmed I, Andrabi NI, Singh G. Advances in the possible treatment of COVID-19: a review. Eur. J. Pharmacol. 883, 173372 (2020).
  Medline CASGoogle Scholar
• 82. Liu X, Liu C, Liu G, Luo W, Xia N. COVID-19: progress in diagnostics, therapy and vaccination. Theranostics 10(17), 7821–7835 (2020).
  Medline CASGoogle Scholar
• 83. Echeverría-Esnal D, Martin-Ontiyuelo C, Navarrete-Rouco ME et al. Azithromycin in the treatment of COVID-19: a review. Expert Rev. Anti. Infect. Ther. 19(2), 147–163 (2021).
  Medline CASGoogle Scholar
• 84. Seyed Hosseini E, Riahi Kashani N, Nikzad H, Azadbakht J, Hassani Bafrani H, Haddad Kashani H. The novel coronavirus disease-2019 (COVID-19): mechanism of action, detection and recent therapeutic strategies. Virology 551, 1–9 (2020).
  MedlineGoogle Scholar
• 85. Group RC, Horby P, Lim WS et al. Dexamethasone in hospitalized patients with COVID-19. N. Engl. J. Med. 384(8), 693–704 (2021).
  MedlineGoogle Scholar
• 86. Ahmadikia K, Hashemi SJ, Khodavaisy S et al. The double-edged sword of systemic corticosteroid therapy in viral pneumonia: a case report and comparative review of influenza-associated mucormycosis versus COVID-19 associated mucormycosis. Mycoses 64(8), 798–808 (2021).
  Medline CASGoogle Scholar
• 87. Kow CS, Hasan SS. Dexamethasone or hydrocortisone in COVID-19? Cleve. Clin. J. Med. 87(12), 715 (2020).
  MedlineGoogle Scholar
• 88. Agresti N, Lalezari JP, Amodeo PP et al. Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: case series of four critically ill patients treated with leronlimab. J. Transl. Autoimmun. 4, 100083 (2021).
  Medline CASGoogle Scholar
• 89. Joshi S, Parkar J, Ansari A et al. Role of favipiravir in the treatment of COVID-19. Int. J. Infect. Dis. 102, 501–508 (2021).
  Medline CASGoogle Scholar
• 90. Agrawal U, Raju R, Udwadia ZF. Favipiravir: a new and emerging antiviral option in COVID-19. Med. J. Armed Forces India 76(4), 370–376 (2020).
  MedlineGoogle Scholar
• 91. Singh SP, Pritam M, Pandey B, Yadav TP. Microstructure, pathophysiology, and potential therapeutics of COVID-19: a comprehensive review. J. Med. Virol. 93(1), 275–299 (2021).
  Medline CASGoogle Scholar
• 92. Tong S, Su Y, Yu Y et al. Ribavirin therapy for severe COVID-19: a retrospective cohort study. Int. J. Antimicrob. Agents 56(3), 106114 (2020).
  Medline CASGoogle Scholar
• 93. Gupta RK, Nwachuku EL, Zusman BE, Jha RM, Puccio AM. Drug repurposing for COVID-19 based on an integrative meta-analysis of SARS-CoV-2 induced gene signature in human airway epithelium. PLoS One 16(9), e0257784 (2021).
  Medline CASGoogle Scholar
• 94. Ng YL, Salim CK, Chu JJH. Drug repurposing for COVID-19: approaches, challenges and promising candidates. Pharmacol. Ther. 228, 107930 (2021). •• Describes drug repurposing approaches.
  Medline CASGoogle Scholar
• 95. Pushpakom S, Iorio F, Eyers PA et al. Drug repurposing: progress, challenges and recommendations. Nat. Rev. Drug Discov. 18(1), 41–58 (2019).
  Medline CASGoogle Scholar
• 96. Pereira CA, Sayé M, Reigada C et al. Computational approaches for drug discovery against trypanosomatid-caused diseases. Parasitology 147(6), 611–633 (2020).
  MedlineGoogle Scholar
• 97. Saberian N, Peyvandipour A, Donato M, Ansari S, Draghici S. A new computational drug repurposing method using established disease-drug pair knowledge. Bioinformatics 35(19), 3672–3678 (2019). • Describes bioinformatic-based approaches for drug repurposing.
  Medline CASGoogle Scholar
• 98. Gyebi GA, Ogunro OB, Adegunloye AP, Ogunyemi OM, Afolabi SO. Potential inhibitors of coronavirus 3-chymotrypsin-like protease (3CL(pro)): an in silico screening of alkaloids and terpenoids from African medicinal plants. J. Biomol. Struct. Dyn. 39(9), 3396–3408 (2020).
  MedlineGoogle Scholar
• 99. Jhamb D, Magid-Slav M, Hurle MR, Agarwal P. Pathway analysis of GWAS loci identifies novel drug targets and repurposing opportunities. Drug Discov. Today 24(6), 1232–1236 (2019).
  Medline CASGoogle Scholar
• 100. Talevi A, Bellera CL. Challenges and opportunities with drug repurposing: finding strategies to find alternative uses of therapeutics. Expert Opin. Drug Discov. 15(4), 397–401 (2020).
  MedlineGoogle Scholar
• 101. Deng C, Ji X, Rainey C, Zhang J, Lu W. Integrating machine learning with human knowledge. iScience 23(11), 101656 (2020).
  MedlineGoogle Scholar
• 102. Zhao K, So H-C. Drug repositioning for schizophrenia and depression/anxiety disorders: a machine learning approach leveraging expression data. IEEE J. Biomed. Heal. Inform. 23(3), 1304–1315 (2019).
  MedlineGoogle Scholar
• 103. Pace JR, DeBerardinis AM, Sail V et al. Repurposing the clinically efficacious antifungal agent itraconazole as an anticancer chemotherapeutic. J. Med. Chem. 59(8), 3635–3649 (2016).
  Medline CASGoogle Scholar
• 104. Lüscher Dias T, Schuch V, Beltrão-Braga PCB et al. Drug repositioning for psychiatric and neurological disorders through a network medicine approach. Transl. Psychiatry 10(1), 141 (2020).
  MedlineGoogle Scholar
• 105. Chavda VP, Vora LK, Vihol DR. COVAX-19^® vaccine: completely blocks virus transmission to non-immune individuals. Clin. Complement. Med. Pharmacol. 1(1), 100004 (2021).
  Google Scholar
• 106. WHO. COVID-19 vaccine tracker and landscape (2022). www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
  Google Scholar
• 107. Karpiński TM, Ożarowski M, Seremak-Mrozikiewicz A, Wolski H, Wlodkowic D. The 2020 race towards SARS-CoV-2 specific vaccines. Theranostics 11(4), 1690–1702 (2021).
  Medline CASGoogle Scholar
• 108. Dong Y, Dai T, Wei Y, Zhang L. A systematic review of SARS-CoV-2 vaccine candidates. Signal Transduct. Target. Ther. 5(1), 237 (2020). •• Summarizes the current vaccine development scenario for COVID-19.
  Medline CASGoogle Scholar
• 109. Holder J. Tracking coronavirus vaccinations around the world. New York Times (2021). www.nytimes.com/interactive/2021/world/covid-vaccinations-tracker.html
  Google Scholar
• 110. Krause PR, Fleming TR, Peto R et al. Considerations in boosting COVID-19 vaccine immune responses. Lancet 398(10308), 1377–1380 (2021). • Role of booster dosing in COVID-19 management.
  Medline CASGoogle Scholar
• 111. Li Y, Tenchov R, Smoot J et al. A comprehensive review of the global efforts on COVID-19 vaccine development. ACS Cent. Sci. 7(4), 512–533 (2021). •• Comprehensive review on the vaccine development scenario for COVID-19.
  MedlineGoogle Scholar
• 112. Wang P, Nair MS, Liu L et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593(7857), 130–135 (2021).
  Medline CASGoogle Scholar
• 113. Lopez Bernal J, Andrews N, Gower C et al. Effectiveness of COVID-19 vaccines against the B.1.617.2 (Delta) variant. N. Engl. J. Med. 385(7), 585–594 (2021). • Vaccine efficacy and the Delta variant.
  MedlineGoogle Scholar
• 114. Mahase E. COVID-19: antibody boost after third dose varies greatly by vaccine, study finds. BMJ 375, n3011 (2021).
  MedlineGoogle Scholar
• 115. Hansen CH, Schelde AB, Moustsen-Helm IR et al. Vaccine effectiveness against SARS-CoV-2 infection with the Omicron or Delta variants following a two-dose or booster BNT162b2 or mRNA-1273 vaccination series: a Danish cohort study. medRxiv doi:10.1101/2021.12.20.21267966 (2021) (Epub ahead of print).
  Google Scholar
• 116. Lu L, Mok BW-Y, Chen L et al. Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients. Clin. Infect. Dis. doi:10.1093/cid/ciab1041 (2021) (Epub ahead of print).
  Google Scholar
• 117. Kyriakidis NC, López-Cortés A, González EV, Grimaldos AB, Prado EO. SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates. NPJ Vaccines 6(1), 28 (2021).
  Medline CASGoogle Scholar
• 118. Bernal JL, Andrews N, Gower C et al. Effectiveness of COVID-19 vaccines against the B.1.617.2 variant. N. Engl. J. Med. 385(7), 585–594 (2021).
  Medline CASGoogle Scholar
• 119. Kozlovskaya LI, Piniaeva AN, Ignatyev GM et al. Long-term humoral immunogenicity, safety and protective efficacy of inactivated vaccine against COVID-19 (CoviVac) in preclinical studies. Emerg. Microbes Infect. 10(1), 1790–1806 (2021).
  Medline CASGoogle Scholar
• 120. Shrotri M, Swinnen T, Kampmann B, Parker EPK. An interactive website tracking COVID-19 vaccine development. Lancet Glob. Heal. 9(5), e590–e592 (2021).
  MedlineGoogle Scholar
• 121. Ng WH, Liu X, Mahalingam S. Development of vaccines for SARS-CoV-2. F1000Res. 9, 991 (2020).
  CASGoogle Scholar
• 122. Mallapaty S. China's COVID vaccines are going global – but questions remain. Nature 593(7858), 178–179 (2021).
  Medline CASGoogle Scholar
• 123. Al Kaabi N, Zhang Y, Xia S et al. Effect of 2 inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: a randomized clinical trial. JAMA 326(1), 35–45 (2021).
  MedlineGoogle Scholar
• 124. Zhang Y, Zeng G, Pan H et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect. Dis. 21(2), 181–192 (2021).
  Medline CASGoogle Scholar
• 125. Chen W-H, Hotez PJ, Bottazzi ME. Potential for developing a SARS-CoV receptor-binding domain (RBD) recombinant protein as a heterologous human vaccine against coronavirus infectious disease (COVID)-19. Hum. Vaccin. Immunother. 16(6), 1239–1242 (2020).
  Medline CASGoogle Scholar
• 126. Heath PT, Galiza EP, Baxter DN et al. Safety and efficacy of NVX-CoV2373 COVID-19 vaccine. N. Engl. J. Med. 385(13), 1172–1183 (2021).
  Medline CASGoogle Scholar
• 127. Tregoning JS, Brown ES, Cheeseman HM et al. Vaccines for COVID-19. Clin. Exp. Immunol. 202(2), 162–192 (2020).
  Medline CASGoogle Scholar
• 128. See I, Su JR, Lale A et al. US case reports of cerebral venous sinus thrombosis with thrombocytopenia after ad26.COV2.S vaccination, March 2 to April 21, 2021. JAMA 325(24), 2448–2456 (2021).
  Medline CASGoogle Scholar
• 129. Jacob JJ, John Fletcher G, Monisha Priya T, Veeraraghavan B, Mutreja A. Relevance of immune response and vaccination strategies of SARS-CoV-2 in the phase of viral red queen dynamics. Indian J. Med. Microbiol. 39(4), 417–422 (2021).
  MedlineGoogle Scholar
• 130. He Q, Mao Q, Zhang J et al. COVID-19 vaccines: current understanding on immunogenicity, safety, and further considerations. Front. Immunol. 12, 669339 (2021).
  Medline CASGoogle Scholar
• 131. Callaway E. Pfizer COVID vaccine protects against worrying coronavirus variants. Nature 593(7859), 325–326 (2021).
  Medline CASGoogle Scholar
• 132. Callaway E. Mix-and-match COVID vaccines trigger potent immune response. Nature 593(7860), 491–491 (2021).
  Medline CASGoogle Scholar
• 133. Dynavax. Press Release. Dynavax and Clover Biopharmaceuticals announce research collaboration to evaluate coronavirus (COVID-19) vaccine candidate with CpG 1018 adjuvant. https://investors.dynavax.com/news-releases/news-release-details/dynavax-and-clover-biopharmaceuticals-announce-research
  Google Scholar
• 134. Martin C, Lowery D. mRNA vaccines: intellectual property landscape. Nat. Rev. Drug Discov. 19(9), 578 (2020).
  Medline CASGoogle Scholar
• 135. Chavda VP, Pandya R, Apostolopoulos V. DNA vaccines for SARS-CoV-2: toward third-generation vaccination era. Expert Rev. Vaccines 20(12), 1549–1560 (2021). • Summarizes DNA vaccine for COVID-19 management.
  Medline CASGoogle Scholar
• 136. Smith TRF, Patel A, Ramos S et al. Immunogenicity of a DNA vaccine candidate for COVID-19. Nat. Commun. 11(1), 2601 (2020).
  Medline CASGoogle Scholar
• 137. Deb P, Molla MMA, Saif-Ur-Rahman KM. An update to monoclonal antibody as therapeutic option against COVID-19. Biosaf. Heal. 3(2), 87–91 (2021). • Summarizes monoclonal antibodies for COVID-19 management.
  MedlineGoogle Scholar
• 138. Weinreich DM, Sivapalasingam S, Norton T et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with COVID-19. N. Engl. J. Med. 384(3), 238–251 (2020).
  MedlineGoogle Scholar
• 139. Razonable RR, Pawlowski C, O'Horo JC et al. Casirivimab-imdevimab treatment is associated with reduced rates of hospitalization among high-risk patients with mild to moderate coronavirus disease-19. EClinicalMedicine 40, 101102 (2021).
  MedlineGoogle Scholar
• 140. Tuccori M, Ferraro S, Convertino I et al. Anti-SARS-CoV-2 neutralizing monoclonal antibodies: clinical pipeline. MAbs 12(1), 1854149 (2020).
  MedlineGoogle Scholar
• 141. Flaherty L. From the feds. J. Emerg. Nurs. 26(3), 242–246 (2000).
  Google Scholar
• 142. Zhao M. Cytokine storm and immunomodulatory therapy in COVID-19: role of chloroquine and anti-IL-6 monoclonal antibodies. Int. J. Antimicrob. Agents 55(6), 105982 (2020).
  Medline CASGoogle Scholar
• 143. Lang FM, Lee KMC, Teijaro JR, Becher B, Hamilton JA. GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches. Nat. Rev. Immunol. 20(8), 507–514 (2020).
  Medline CASGoogle Scholar
• 144. Patterson BK, Seethamraju H, Dhody K et al. CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14. Int. J. Infect. Dis. 103, 25–32 (2021).
  Medline CASGoogle Scholar
• 145. Rosas IO, Bräu N, Waters M et al. Tocilizumab in hospitalized patients with severe COVID-19 pneumonia. N. Engl. J. Med. 384(16), 1503–1516 (2021).
  Medline CASGoogle Scholar
• 146. Mariette X, Hermine O, Tharaux P-L et al. Effectiveness of tocilizumab in patients hospitalized with COVID-19: a follow-up of the CORIMUNO-TOCI-1 randomized clinical trial. JAMA Intern. Med. 181(9), 1241–1243 (2021).
  Medline CASGoogle Scholar
• 147. Pinto D, Park YJ, Beltramello M et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature 583(7815), 290–295 (2020).
  Medline CASGoogle Scholar
• 148. Ju B, Zhang Q, Ge J et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature 584(7819), 115–119 (2020). •• Summarizes monoclonal antibodies for COVID-19 management.
  Medline CASGoogle Scholar
• 149. Shanmugaraj B, Rattanapisit K, Manopwisedjaroen S, Thitithanyanont A, Phoolcharoen W. Monoclonal antibodies B38 and H4 produced in Nicotiana benthamiana neutralize SARS-CoV-2 in vitro. Front. Plant Sci. 11, 589995 (2020).
  MedlineGoogle Scholar
• 150. Wang C, Li W, Drabek D et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat. Commun. 11(1), 1–6 (2020).
  MedlineGoogle Scholar
• 151. Khosla S, Hofbauer LC. Osteoporosis treatment: recent developments and ongoing challenges. Lancet Diabetes Endocrinol. 5(11), 898–907 (2017).
  MedlineGoogle Scholar
• 152. Rogers TF, Zhao F et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science 369(6506), 956–963 (2020).
  Medline CASGoogle Scholar
• 153. Du S, Cao Y, Zhu Q et al. Structurally resolved SARS-CoV-2 antibody shows high efficacy in severely infected hamsters and provides a potent cocktail pairing strategy. Cell 183(4), 1013–1023.e13 (2020).
  Medline CASGoogle Scholar
• 154. Seydoux E, Homad LJ, MacCamy AJ et al. Analysis of a SARS-CoV-2-infected individual reveals development of potent neutralizing antibodies with limited somatic mutation. Immunity 53(1), 98–105.e5 (2020).
  Medline CASGoogle Scholar
• 155. Mehta P, Porter JC, Manson JJ et al. Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities. Lancet Respir. Med. 8(8), 822–830 (2020).
  Medline CASGoogle Scholar
• 156. Benucci M, Giannasi G, Cecchini P et al. COVID-19 pneumonia treated with sarilumab: a clinical series of eight patients. J. Med. Virol. 92(11), 2368–2370 (2020).
  Medline CASGoogle Scholar
• 157. Landi L, Ravaglia C, Russo E et al. Blockage of interleukin-1β with canakinumab in patients with COVID-19. Sci. Rep. 10(1), 1–9 (2020).
  MedlineGoogle Scholar
• 158. Temesgen Z, Assi M, Shweta FNU et al. GM-CSF neutralization with lenzilumab in severe COVID-19 pneumonia: a case–cohort study. Mayo Clin. Proc. 95(11), 2382–2394 (2020).
  Medline CASGoogle Scholar
• 159. Mi T, Burgess K. Striking similarities between CDRs in some mAbs that neutralize COVID-19. ACS Med. Chem. Lett. 11(9), 1663–1666 (2020).
  Medline CASGoogle Scholar
• 160. Alsaadi EAJ, Jones IM. Membrane binding proteins of coronaviruses. Future Virol. 14(4), 275–286 (2019).
  Google Scholar
• 161. Yavuz SŞ, Ünal S. Antiviral treatment of COVID-19. Turk. J. Med. Sci. 50, 611–619 (2020).
  Medline CASGoogle Scholar
• 162. Khare P, Sahu U, Pandey SC, Samant M. Current approaches for target-specific drug discovery using natural compounds against SARS-CoV-2 infection Prashant. Virus Res. 290, 1–16 (2020).
  Google Scholar
• 163. Altay O, Mohammadi E, Lam S et al. Current status of COVID-19 therapies and drug repositioning applications. iScience 23(7), 101303 (2020).
  Medline CASGoogle Scholar
• 164. Zhou P, Yang X, Wang X et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(1), 270–280 (2020).
  Medline CASGoogle Scholar
• 165. Zhang H, Penniger J M, Li Y, Zhong N, Slutsky A S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 46(4), 586–590 (2020).
  Medline CASGoogle Scholar
• 166. Huang M-T, Ghai G, Ho C-T. Inflammatory process and molecular targets for anti-inflammatory nutraceuticals. Compr. Rev. Food Sci. Food Saf. 3(4), 127–139 (2004).
  Medline CASGoogle Scholar
• 167. Bahbah EI, Negida A, Nabet MS. Purposing saikosaponins for the treatment of COVID-19. Med. Hypotheses 140, 109782 (2020).
  Medline CASGoogle Scholar
• 168. Kim DE, Min JS, Jang MS et al. Natural bis-benzylisoquinoline and cepharanthine inhibit human coronavirus OC43 infection of MRC-5 human lung cells. Biomolecules 9(696), 1–16 (2019).
  Google Scholar
• 169. Lin C-W, Tsai F-J, Tsai C-H et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Res. 68(1), 36–42 (2005).
  Medline CASGoogle Scholar
• 170. Ryu YB, Jeong HJ, Kim JH et al. Biflavonoids from Torreya nucifera displaying SARS-CoV 3CLpro inhibition. Bioorg. Med. Chem. 18(22), 7940–7947 (2010).
  Medline CASGoogle Scholar
• 171. Veeramani C, Alsaif MA, Al-Numair KS. Herbacetin, a flaxseed flavonoid, ameliorates high percent dietary fat induced insulin resistance and lipid accumulation through the regulation of hepatic lipid metabolizing and lipid-regulating enzymes. Chem. Biol. Interact. 288, 49–56 (2018).
  Medline CASGoogle Scholar
• 172. Sherif YE, Gabr SA, Hosny NM, Alghadir AH, Alansari R. Phytochemicals of Rhus spp. as potential inhibitors of the SARS-CoV-2 main protease: molecular docking and drug-likeness study. Evidence-Based Complement. Altern. Med. 2021, 8814890 (2021).
  Google Scholar
• 173. Lim H, Son KH, Chang HW, Bae K, Kang SS, Kim HP. Anti-inflammatory activity of pectolinarigenin and pectolinarin isolated from Cirsium chanroenicum. Biol. Pharm. Bull. 31(11), 2063–2067 (2008).
  Medline CASGoogle Scholar
• 174. Lau K-M, Lee K-M, Koon C-M et al. Immunomodulatory and anti-SARS activities of Houttuynia cordata. J. Ethnopharmacol. 118(1), 79–85 (2008).
  MedlineGoogle Scholar
• 175. Alam S, Sarker MMR, Afrin S et al. Traditional herbal medicines, bioactive metabolites, and plant products against COVID-19: update on clinical trials and mechanism of actions. Front. Pharmacol. 12, 1248 (2021). • Role of herbal remedies in COVID-19 management.
  Google Scholar
• 176. Wen C-C, Shyur L-F, Jan J-T et al. Traditional Chinese medicine herbal extracts of Cibotium barometz, Gentiana scabra, Dioscorea batatas, Cassia tora, and Taxillus chinensis inhibit SARS-CoV replication. J. Tradit. Complement. Med. 1(1), 41–50 (2011).
  MedlineGoogle Scholar
• 177. Mazraedoost S, Behbudi G, Mousavi SM, Hashemi SA. COVID-19 treatment by plant compounds. AANBT 2(1), 23–33 (2021).
  CASGoogle Scholar
• 178. Subedi L, Tchen S, Gaire BP, Hu B, Hu K. Adjunctive nutraceutical therapies for COVID-19. Int. J. Mol. Sci. 22(4), 1963 (2021).
  Medline CASGoogle Scholar
• 179. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective. Int. J. Biol. Sci. 16(10), 1708–1717 (2020).
  Medline CASGoogle Scholar
• 180. Frick D, Lam A. Understanding helicases as a means of virus control. Curr. Pharm. Des. 12(11), 1315–1338 (2006).
  Medline CASGoogle Scholar
• 181. Karpe YA, Lole KS. NTPase and 5′ to 3′ RNA duplex-unwinding activities of the hepatitis E virus helicase domain. J. Virol. 84(7), 3595–3602 (2010).
  Medline CASGoogle Scholar
• 182. Jo S, Kim S, Shin DH, Kim M. Inhibition of SARS-CoV 3CL protease by flavonoids. J. Enzyme Inhib. Med. Chem. 35(1), 145–151 (2019).
  Google Scholar
• 183. Koulgi S, Jani V, Uppuladinne M, Sonavane U, Nath AK. Drug repurposing studies targeting SARS-CoV-2: an ensemble docking approach on drug target 3C-like protease (3CL pro). J. Biomol. Struct. Dyn. 39(15), 5735–5755 (2020).
  MedlineGoogle Scholar
• 184. Hilgenfeld R. From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design. FEBS J. 281(1), 4085–4096 (2014).
  Medline CASGoogle Scholar
• 185. Fung KP, Leung PC, Tsui KW et al. Immunomodulatory activities of the herbal formula kwan du bu fei dang in healthy subjects: a randomised, double-blind, placebo-controlled study. Hong Kong Med. J. 17(2), 41–43 (2011).
  MedlineGoogle Scholar
• 186. Kumar P, Kumar M, Bedi O et al. Role of vitamins and minerals as immunity boosters in COVID-19. Inflammopharmacology 29(4), 1001–1016 (2021). • Role of vitamins in COVID-19 management.
  Medline CASGoogle Scholar
• 187. Gombart AF, Pierre A, Maggini S. A review of micronutrients and the immune system – working in harmony to reduce the risk of infection. Nutrients 12(1), 236 (2020).
  CASGoogle Scholar
• 188. Lordan R, Rando HM, COVID-19 Review Consortium, Greene CS. Dietary supplements and nutraceuticals under investigation for COVID-19 prevention and treatment. mSystems 6(3), e00122–e21 (2021).
  Medline CASGoogle Scholar
• 189. Savant S, Srinivasan S, Kruthiventi AK. Potential nutraceuticals for COVID-19. Nutr. Diet. Suppl. 13, 25–51 (2021). • Role of nutraceuticals in COVID-19 management.
  Google Scholar
• 190. Bauer SR, Kapoor A, Rath M, Thomas SA. What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine for prevention or treatment of COVID-19? Cleve. Clin. J. Med. doi:10.3949/ccjm.87a.ccc046 (2020) (Epub ahead of print).
  MedlineGoogle Scholar
• 191. Altay O, Arif M, Li X et al. Combined metabolic activators accelerates recovery in mild-to-moderate COVID-19. Adv. Sci. 8(17), 2101222 (2021).
  CASGoogle Scholar
• 192. Obayan AE. Overview of the rationale for L-glutamine treatment in moderate–severe COVID-19. J. Infect. Dis. Epidemiol. 7, 187 (2021).
  Google Scholar
• 193. Hemilä H, de Man AME. Vitamin C and COVID-19. Front. Med. 7, 1013 (2021).
  Google Scholar
• 194. Wallace TC, Reider C, Fulgoni VL. Calcium and vitamin D disparities are related to gender, age, race, household income level, and weight classification but not vegetarian status in the United States: analysis of the NHANES 2001–2008 data set. J. Am. Coll. Nutr. 32(5), 321–330 (2013).
  Medline CASGoogle Scholar
• 195. Grant WB, Lahore H, McDonnell SL et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 12(4), 1–19 (2020).
  Google Scholar
• 196. Li R, Wu K, Li Y et al. Revealing the targets and mechanisms of vitamin A in the treatment of COVID-19. Aging (Albany NY) 12(15), 15784–15796 (2020).
  Medline CASGoogle Scholar
• 197. Goyal P, Choi JJ, Pinheiro LC et al. Clinical characteristics of COVID-19 in New York City. N. Engl. J. Med. 382(24), 2372–2374 (2020).
  MedlineGoogle Scholar
• 198. Zhang C, Shi L, Wang F-S. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol. Hepatol. 5(5), 428–430 (2020).
  MedlineGoogle Scholar
• 199. Bhatraju PK, Ghassemieh BJ, Nichols M et al. COVID-19 in critically ill patients in the Seattle region – case series. N. Engl. J. Med. 382(21), 2012–2022 (2020).
  Medline CASGoogle Scholar
• 200. Chavda VP, Apostolopoulos V. Mucormycosis – an opportunistic infection in the aged immunocompromised individual: a reason for concern in COVID-19. Maturitas 154, 58–61 (2021). • Mucormycosis associated with COVID-19.
  Medline CASGoogle Scholar
• 201. Singh AK, Singh R, Joshi SR, Misra A. Mucormycosis in COVID-19: a systematic review of cases reported worldwide and in India. Diabetes Metab. Syndr. Clin. Res. Rev. 15(4), 102146 (2021).
  Google Scholar