Reviews on remdesivir in Covid-19 treatment

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Remdesivir (GS-5734; Gilead Sciences Inc., US) is an investigational nucleoside analog that acts as a competitive inhibitor of viral RNAdependent RNA polymerase (RdRp). In the body, remdesivir is transformed into an active molecule known as GS-441524. The results of in vitro, in vivo studies and clinical trials have been reviewed [1].

Remdesivir was found to have an EC50 of 0.77 μM against SARS-CoV-2 in Vero E6 cells. This activity of remdesivir was higher than that of the other drugs used in the study, such as ribavirin, penciclovir, favipiravir, nafamostat, nitazoxanide, and chloroquine, which showed EC50 values of 109.5, 95.96, 61.88, 22.50, 2.12, and 1.13 μM, respectively.

A recent study showed that remdesivir administration to SARS-CoV-2-infected rhesus macaques improved pulmonary lesions, according to radiographs; reduced viral titers in bronchoalveolar lavage after 12 h of treatment; and reduced the viral load in the lungs after 7 days of treatment. Moreover, the remdesivir-treated animals did not show any signs of pulmonary disease.

The first randomized, double-blind, placebo-controlled, multicenter clinical trial was reported on April 29, 2020. The study was conducted in China with 237 patients (158 in the remdesivir group and 79 in the placebo control group), and the primary endpoint was the time taken to achieve clinical improvement. The study revealed that treatment with remdesivir did not lead to a significant reduction in the time taken to achieve clinical improvement. In addition, mortality and viral clearance time in patients with severe COVID-19 were not significantly different from those in the placebo group, suggesting that remdesivir had poor clinical benefits. This further suggests that in COVID-19, viral propagation is not the main factor responsible for disease severity. On this account, the antiviral properties of remdesivir will not be beneficial. The severity of COVID-19 has been associated with the cytokine release storm, suggesting that host immune responses play an important role in this event. Therefore, a combination of remdesivir with immunosuppressants (for example sarilumab, an IL-6 the inhibitor) and/or other antiviral agents might potentiate the antiviral activity of remdesivir and mitigate the immunopathological injury caused by excessive immune effectors. Nonetheless, during the same trial, in remdesivir-treated patients with COVID-19, especially those treated within 10 days of symptom onset, faster clinical improvement was observed than that in the placebo group. Unfortunately, the study was terminated prematurely owing to the occurrence of more frequent adverse events in the remdesivir group than in the placebo group. Considering these findings, the small sample size, and because the study was unexpectedly terminated, it may be insufficient to elucidate the efficacy of remdesivir. Furthermore, the pharmacokinetics of remdesivir and its active metabolite in the respiratory tracts and/or other infected organs remain largely unknown in patients with COVID-19. Therefore, the results of ongoing clinical trials are warranted to provide conclusive evidence regarding the efficacy of remdesivir in patients with COVID-19.

It was concluded that remdesivir has been used in several countries as an emergency drug for patients with COVID-19, and some patients showed improved clinical outcomes. However, large-scale clinical
trials should be conducted to confirm the efficacy of remdesivir in treating patients with COVID-19.

Another review [2] on clinical trials concluded that remdesivir was effective in the treatment of COVID-19. The drug has side effects, but the symptoms were mild and disappeared immediately after discontinuation of medication.

  1. Frediansyah A, Nainu F, Dhama K, Mudatsir M, Harapan H: Remdesivir and its antiviral activity against COVID-19: A systematic review. Clin Epidemiol Glob Health. 2021 Jan-Mar;9:123-127. doi: 10.1016/j.cegh.2020.07.011.
  2. 2. Hong YN, Xu J, Sasa GBK, Zhou KX, Ding XF: Remdesivir as a broad-spectrum antiviral drug against COVID-19. Eur Rev Med Pharmacol Sci. 2021 Jan;25(1):541-548. doi: 10.26355/eurrev_202101_24426.


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