Emerging Therapeutic Modalities against COVID-19
Abstract
:1. Introduction
2. Clinical Approaches
2.1. Repurposed Drugs
2.1.1. Lopinavir/Ritonavir
2.1.2. Chloroquine/Hydroxychloroquine
2.1.3. Azithromycin
2.1.4. Arbidol
2.1.5. Serine Protease Inhibitors
2.1.6. Low Dose Heparins
2.1.7. Other Drugs
2.2. Immunomodulators
2.2.1. Janus Kinase (JAK) Inhibitors
2.2.2. Fingolimod
2.2.3. Aviptadil
2.2.4. Thalidomide
2.2.5. Monoclonal Antibodies (mAbs)
2.2.6. Interferons
2.3. Investigational Drugs
2.3.1. Remdesivir
2.3.2. Tradipitant
2.3.3. ASC09 (TMC 310911)
2.3.4. FT516
2.3.5. CD24Fc
2.3.6. Others
2.4. Convalescent Plasma Therapy (CPT)
2.5. SARS-CoV-2 Vaccine Candidates
2.5.1. mRNA-Based Vaccines
2.5.2. INO 4800 DNA Vaccine
2.5.3. ChAdOx1 nCoV-19 Vaccine
2.5.4. COVID-19 Artificial Antigen-Presenting Cells (aAPC) Vaccine
2.5.5. Synthetic Minigene Vaccine
2.5.6. Ad5-nCoV COVID-19 Vaccine
2.6. Mesenchymal Stem Cell (MSC) Therapy
3. Emerging Therapeutics
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Drug(s) | Antiviral Activity | Number of Clinical Trials | Reference |
---|---|---|---|
Lopinavir/ritonavir | Coronavirus protease (CLpro) inhibitor | 18 | [26,27] |
Chloroquine/ hydroxy-chloroquine | i. Acidification of endosomes/lysosomes ii. Impair glycosylation of angiotensin converting enzyme 2 (ACE2) | 117 | [28,29,30] |
Azithromycin | i. Endosome acidification ii. Immunomodulatory | 34 | [31] [32] |
Arbidol | i. Interference with virus trafficking ii. Blocks trimerization of spike (S) glycoprotein | 3 | [33] [34] |
Camostat mesylate | Serine protease (TMPRSS2) inhibitor | 3 | [35] |
Nafamostat mesylate | Serine protease (TMPRSS2) inhibitor | 2 | [36] |
Nitazoxanide | Inhibition of cytokine production | 5 | [37] |
Clevudine | Inhibition of viral RNA synthesis | 1 | [38,39] |
Favipiravir | RNA-dependent RNA polymerase (RdRp) inhibitor | 7 | [40] |
Oseltamivir | Neuraminidase inhibitor | 4 | [41] |
Darunavir/cobicistat | HIV protease inhibitor/ CYP3A inhibitor | 1 | [42] |
Selinexor | Selective inhibitor nuclear export (SINE) | 2 | [43] |
Ivermectin | Inhibition of nuclear importin (IMPα/β) transporter | 12 | [44] |
Carrimycin | Prevent respiratory tract infection | 1 | [45] |
Ribavirin | i. RdRp inhibitor ii. Immunomodulatory | 2 | [46,47] |
Immunomodulators | |||
Baricitinib | Janus kinase (JAK1 and JAK2) inhibitor | 6 | [48] |
Ruxolitinib | Janus kinase inhibitor | 8 | [49] |
Fingolimod | Anti-inflammatory (sphingosine-1-phosphate receptor subtype 1 modulatory) | 1 | [50] |
Aviptadil | i. Broncho- and vasodilation ii. Anti-inflammatory | 2 | [51] |
Thalidomide | Anti-inflammatory | 2 | [52] |
Tocilizumab | IL-6 antagonist | 18 | [53] |
Bevacizumab | Vascular endothelial growth factor (VEGF) inhibitor | 2 | [54] |
Eculizumab | Complement protein C5 inhibitor | 3 | [55] |
Interferons | Immune activation against virus | 18 | [56,57] |
Drugs | Antiviral Activity | Number of Clinical Trials | Reference |
---|---|---|---|
Remdesivir | RdRp inhibitor | 10 | [171] |
Tradipitant | Neurokinin-1 (NK1) antagonist | 1 | [173] |
ASC09 or TMC 310911 | Human immunodeficiency virus-1 (HIV-1) protease inhibitor | 1 | [174] |
FT516 | i. Genetically modified natural killer (NK) cells ii. Enhances cytotoxic response against SARS-CoV-2 | 1 | [175] |
CD24Fc | Immune check point and prevents hyperinflammation | 1 | [176,177] |
XPro1595 | Tumor necrosis factor (TNF) inhibitor | 1 | - |
LY3127804 | Angiopoietin-2 antibody | 1 | [178] |
Leronlimab | C-C chemokine receptor type 5 (CCR5) antibody | 2 | [179] |
Vaccine | Antiviral Activity | Clinical Trial | Reference |
---|---|---|---|
mRNA1273 | mRNA based vaccine candidate encoding for complete S protein of SARS-CoV-2 Delivery platform: lipid nanoparticles (LNP) | NCT04470427 Phase 3 Status: Recruiting | [192,199] |
BNT162 | 4 mRNA-based vaccine candidates encoding either
| NCT04368728 Phase 1/2 Status: Active, Not Recruiting | [201,202] |
ChAdOx1 nCoV-19 | Chimpanzee adenovirus vector encoding S glycoprotein of SARS-CoV-2 | NCT04400838 Phase 2/3 Status: Recruiting | [203,204] |
COVID-19 aAPC | Artificial antigen-presenting cells (aAPC) modified using lentivirus vector to express
| NCT04299724 Phase 1 Status: Recruiting | [205,206] |
Synthetic Minigene Vaccine or LV-SMENP-DC | i. Genetically modified dendritic cells (DCs) via lentivirus vector to express
| NCT04276896 Phase 1/2 Status: Recruiting | - |
Ad5-nCoV COVID-19 | Replication defective adenovirus 5 vector (Ad5) encoding full length S protein of SARS-coV-2 virus | NCT04398147 Phase 2 Status: Active, Not Recruiting | [207] |
INO 4800 | Plasmid DNA encoding SARS-CoV-2 proteins Delivery platform: Cellectra® (electroporation) | NCT04336410 Phase 1 Status: Recruiting NCT04447781 Phase I/IIa Status: Not yet recruiting | [208] |
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Malik, S.; Gupta, A.; Zhong, X.; Rasmussen, T.P.; Manautou, J.E.; Bahal, R. Emerging Therapeutic Modalities against COVID-19. Pharmaceuticals 2020, 13, 188. https://doi.org/10.3390/ph13080188
Malik S, Gupta A, Zhong X, Rasmussen TP, Manautou JE, Bahal R. Emerging Therapeutic Modalities against COVID-19. Pharmaceuticals. 2020; 13(8):188. https://doi.org/10.3390/ph13080188
Chicago/Turabian StyleMalik, Shipra, Anisha Gupta, Xiaobo Zhong, Theodore P. Rasmussen, Jose E. Manautou, and Raman Bahal. 2020. "Emerging Therapeutic Modalities against COVID-19" Pharmaceuticals 13, no. 8: 188. https://doi.org/10.3390/ph13080188