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Table 2 Published clinical trials of drugs against SARS-CoV-2

From: Human coronaviruses and therapeutic drug discovery

Step Target Drug Result Population Methodology ID Reference number
Positive Negative
Attachment and entry Viral envelope Arbidol/umifenovir N/A Umifenovir did not improve the prognosis or accelerate SARS-CoV-2 clearance in non-ICU patients 81 moderates to severe COVID-19 patients (umifenovir vs control = 45: 36) Single-centre, retrospective N/A [29]
The ability of arbidol to reduce SARS-CoV-2 RNA load is better than lopinavir–ritonavir N/A 50 COVID-19 patients (lopinavir/ritonavir vs arbidol = 34:16) N/A N/A [27]
Endosomal acidification Hydroxychloroquine N/A Hydroxychloroquine did not induce SARS-CoV-2 negative conversion. It has cardiotoxicity 150 patients with mainly persistent mild to moderate COVID-19 (hydroxychloroquine + standard of care vs standard of care alone = 75:75) Multicenter, open label, randomized controlled ChiCTR2000029868 [33]
Chloroquine diphosphate N/A Chloroquine diphosphate did not reduce mortality and may extend QT intervals 81 patients (high-dosage vs low-dosage group = 41:40) Parallel, double-masked, randomized, phase IIb N/A [34]
Replicase protein expression Mpro (3C-like protease) (nsp5) Lopinavir/ritonavir N/A Lopinavir–ritonavir did not reduce mortality or the time to clinical improvement 199 COVID-19 adults (lopinavir–ritonavir:standard-care = 99:100) Randomized, controlled, open-label ChiCTR2000029308 [49]
N/A Lopinavir–ritonavir did not reduce mortality or prevent progression 5040 (lopinavir/ritonavir:usual care = 1616:3424) Randomised, controlled, open-label, platform NCT04381936 [48]
Replication, transcription and translation Nsp12 Remdesivir By day 28, 10-day remdesivir group had a better clinical status distribution than standard care group Remdesivir did not reduce the length of hospitalization or oxygen therapy 584 moderate COVID-19 patients (10-day remdesivir:5-day remdesivir:standard care = 197:199:200) Randomized, controlled, open-label NCT04292730 [53]
Remdesivir reduces the duration of hospitalization and infection N/A 1059 COVID-19 adults with lower respiratory tract infection (remdesivir:placebo = 538:521) Double-blind, randomized, placebo-controlled NCT04280705 [54]
N/A There is no significant clinical difference between a 5-day course and a 10-day course of remdesivir 397 severe COVID-19 patients (5-day remdesivir:10-day remdesivir = 200:197) Randomized, open-label NCT04292899 [52]
N/A Remdesivir did not reduce time to clinical improvement 237 COVID-19 adults (10- day remdesivir vs placebo = 158:79) Randomised, double-blind, placebo-controlled, multicentre NCT04257656 [51]
Favipiravir Favipiravir leads to faster viral clearance and better chest CT changes than patients treated with lopinavir/ritonavir N/A 80 COVID-19 patients (favipiravir vs lopinavir/ritonavir = 35:45) Open-label comparative controlled ChiCTR2000029600 [59]
Immunology IFN supplement IFN-α2b Among severe to critical COVID-19 patients, early treatment with IFN-α2b reduced in-hospital mortality IFN-α2b did not benefit significantly in moderately ill patients 242 (IFN + LPV/r, IFN + UFV, IFN alone) of 446 COVID-19 patients received IFN-α2b Retrospective, multicenter   [100]
Protective antibody supplement Convalescent plasma Convalescent plasma is most effective in early application and reduces mortality N/A 39 patients with severe to life-threatening COVID-19 (convalescent plasma vs controls = 1:4 and 1:2 ratios) Retrospective, propensity score–matched case–control N/A [119]
Convalescent plasma was associated with antiviral activity Convalescent plasma did not significantly reduce time to the clinical improvement 103 patients with severe to life-threatening COVID-19 (Convalescent plasma in addition to standard treatment vs standard treatment alone = 52:51) Open-label, multicenter, randomized, prospective ChiCTR2000029757 [120]
Cytokine storm Corticosteroids Early, low-dose and short-term application of methylprednisolone helped reach better clinical outcomes in severe patients with COVID-19 pneumonia N/A 46 severe patients with COVID-19 pneumonia (26 of them received extra low-dose and short-term methylprednisolone treatment) Retrospective N/A [122]
For severe COVID-19 patients, methylprednisolone pulse promoted clinical improvements and reduced mortality N/A 68 severe COVID-19 patients (methylprednisolone vs standard care alone = 34:34) Single-blind, randomized, controlled N/A [123]
IL-6R Tocilizumab N/A Tocilizumab showed no benefit on disease progression compared with standard care. (early shutdown) 126 adults with COVID-19 pneumonia and PaO2/FIO2 ratio between 200 and 300 mmHg (tocilizumab vs supportive care = 60:66) Prospective, open-label, randomized NCT04346355 [127]
N/A Tocilizumab did not promote clinical improvements or reduced mortality 131 COVID-19 patients with moderate or severe pneumonia requiring oxygen but without ventilation or admission to the ICU (tocilizumab vs usual care alone = 64:67) Multicenter, open-label, Bayesian randomized NCT04331808 [126]
Tocilizumab reduced serious infections Tocilizumab did not prevent intubation or death in moderately ill hospitalized patients with COVID-19 243 hospitalized COVID-19 patients (standard care + tocilizumabvs vs standard care + placebo = 162:81) Randomized, double-blind, placebo-controlled NCT04356937 [125]
  1. N/A: not applicable; ICU: intensive care unit; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus disease 2019; CT: computed tomography; IFN: Interferon; IL: interleukin; PaO2/FIO2: OXYGENATION index
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