Safety Consequences of Off-Label Drugs Used for COVID-19

Imam

et al. 2022

Preprint

We previously showed that Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin inhibit SARS-COV-2 induced cytopathic effect (CPE) in Vero cells. In this study and using validated quantitative neutral red assay, we show that the inhibition of CPE is concentration dependent with Inhibitory Concentration-50(IC50) of 3.27 microM, 4.23 microM, 9.29 microM, 3.19 microM and 84.31 microM respectively. Furthermore, Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit SARS-CoV-2 Papain-like Protease with IC50 of 0.94 microM, 0.88 microM, 1.14 microM, 1.07 microM, 1.51 microM respectively and the main protease(MPRO) with IC50 of 1.35 microM, 1.25 microM, 7.36 microM, 1.15 microM, and 2.44 microM respectively. The IC50 for all the drugs, except ivermectin, are at the clinically achievable plasma concentration in human, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by Ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.

Section: Discussionmentioning

confidence: 69%

“…Such Preliminary Insight documentation should be routine in off-label prescriptions but may not and cannot replace randomized trials. In this regard, risk of abuse of documented off-label prescription, like using it as convenient alternative to clinical trials, should be recognized and mitigated 41 .…”

Section: Discussionmentioning

confidence: 99%

Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and M^PROof SARS-CoV-2

Imam

et al. 2022

Preprint

Front. Cell. Infect. Microbiol.

“…Such preliminary insight documentation should be routine in off-label prescriptions but may not and cannot replace randomized trials. In this regard, the risk of abuse of documented off-label prescription, like using it as a convenient alternative to clinical trials, should be recognized and mitigated ( Dasgupta, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2

Bello,

Imam,

Bello

et al. 2023

BackgroundAlthough tremendous success has been achieved in the development and deployment of effective COVID-19 vaccines, developing effective therapeutics for the treatment of those who do come down with the disease has been with limited success. To repurpose existing drugs for COVID-19, we previously showed, qualitatively, that erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit SARS-COV-2-induced cytopathic effect (CPE) in Vero cells.AimThis study aimed to quantitatively explore the inhibition of SARS-CoV-2-induced CPE by erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin and to determine the effect of these drugs on SARS-CoV-2 papain-like protease and 3CL protease (MPRO) enzymes.MethodsNeutral red (3-amino-7-dimethylamino-2-methyl-phenazine hydrochloride) cell viability assay was used to quantify CPE after infecting pre-treated Vero cells with clinical SARS-Cov-2 isolates. Furthermore, SensoLyte® 520 SARS-CoV-2 papain-like protease and SensoLyte® 520 SARS-CoV-2 MPRO activity assay kits were used to evaluate the inhibitory activity of the drugs on the respective enzymes.ResultsErythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibit SARS-CoV-2-induced CPE in Vero cells, with inhibitory concentration-50 (IC50) values of 3.27 µM, 4.23 µM, 9.29 µM, 3.19 µM, and 84.31 µM, respectively. Furthermore, erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibited SARS-CoV-2 papain-like protease with IC50 values of 0.94 µM, 0.88 µM, 1.14 µM, 1.07 µM, and 1.51 µM, respectively, and inhibited the main protease (MPRO) with IC50 values of 1.35 µM, 1.25 µM, 7.36 µM, 1.15 µM, and 2.44 µM, respectively.ConclusionThe IC50 for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.

Proceedings of the Annual Hawaii International Conference on System Sciences

“…With an increase in the role of social networks in seeking and managing their care [52] and individuals replacing mainstream sources with social media as trusted sources of information [53,54] the problem of misinformation and midinformation during the pandemic lead to detrimental consequences 3 . Additionally, the networked nature of Twitter does not allow messages to receive equal attention, and there is a 'giant effect' in rumour propagation since influential accounts with larger audiences can accelerate the snowballing of otherwise obscure information [55,28].…”

Section: Information Ambiguity: Misinformation 'Midinformation' and Rumoursmentioning

confidence: 99%

“…With the continuing lack of a dedicated COVID related drug, and uncertainty over access to vaccines at the time, the period saw much speculation around unproven cures and therapies. While these drugs are often put on off-label lists for compassionate usage, several studies outline the impacts of their cavalier usage in terms of shortages for other diseases [2] and the safety consequences [3].…”

Section: Introductionmentioning

confidence: 99%

Virality and the Virus: Drugs and Cures on Twitter During the COVID-19 Crisis in India

Mishra¹,

Akbar²,

Shekhawat³

et al. 2022

Social media platforms often become environments of information ambiguity during crisis events. We studied the discussion around four "cures" for COVID-19 in India, where the highest number of cases were recorded between 2020 and May 2021, focusing on the role played by high network accounts on social media such as those of journalists, politicians, and celebrities. We find that information scarcity and anxiety among citizens enabled non-experts, particularly the aforementioned social media influencers. We find that this undermined institutional sources of information and led to massive spikes in online interest around unproven cures during the peak of the crisis.