FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy

Drożdżal, Sylwester; Rosik, Jakub; Lechowicz, Kacper; Machaj, Filip; Kotfis, Katarzyna; Ghavami, Saeid; Łos, Marek

doi:10.1016/j.drup.2020.100719

Cited by 132 publications

(142 citation statements)

References 129 publications

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“…Up to this point, HCQ has been used for the treatment of malaria or autoimmune diseases such as rheumatoid arthritis, discoid and systemic lupus erythematosus (Plaquenil Label, 2017 ; Plaquenil SmPC, 2020 ). However, HCQ seems to offer a dual beneficial action for COVID-19 patients, as it exerts both immunomodulatory and antiviral effects (Drożdżal et al., 2020 ). In fact, some recent studies have revealed the drug’s in vitro antiviral activity (Liu et al., 2020b ; PAHO/WHO, 2020 ; Yao et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Considering all the above and based on the reported antiviral activity of the compound (Drożdżal et al., 2020 ; Liu et al., 2020b ; Yao et al., 2020 ), there is currently a need to rationalize the administered dosing schemes in order to maximize the efficacy and safety of HCQ in patients with COVID-19. Eventually, additional time is needed in order to retrieve concrete results from new in vitro and in vivo studies specifically designed for HCQ against COVID-19.…”

Section: Introductionmentioning

confidence: 99%

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Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations

et al. 2020

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1. During the recent COVID-19 outbreak hydroxychloroquine (HCQ) has been proposed as a safe and effective therapeutic option. However, a wide variety of dosing schemes has been applied in the clinical practice and tested in clinical studies. 2. An extended literature survey was performed investigating the pharmacokinetics, the efficacy and safety of HCQ in COVID-19 treatment. Population pharmacokinetic models were retrieved from the literature and after evaluation and assessment one was selected in order to perform simulations. 3. The most commonly applied dosing schemes were explored for patients with different weights and different levels of HCQ clearance impairment. Model-based simulations of HCQ concentrations revealed that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instance, the dosing scheme proposed for a 70 kg adult with moderate COVID-19 symptoms would be 600 mg upon diagnosis, 400 mg after 12 h, 300 mg after 24 h, 200 mg after 36 h, followed by 200 mg BID for 4 d, followed by 200 mg OD for 5 d. 4. Based on the results from simulations performed and the currently published knowledge regarding HCQ in COVID-19 treatment, this study provides evidence that a high loading dose followed by sparse doses could offer significant benefits to the patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations

et al. 2020

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“…The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported on December 2019 from Wuhan City, Hubei, China ( Zhu et al, 2020 ; Lu et al, 2020 ) and is currently causing major concern in the medical community, as it exhibits faster human-to-human transmission often combined with asymptomatic, or minimally symptomatic course of the infection ( Drożdżal et al, 2020 ). These two factors are perhaps the major contribution of the rapid propagation of the virus.…”

Section: Introductionmentioning

confidence: 99%

Current status of antivirals and druggable targets of SARS CoV-2 and other human pathogenic coronaviruses

Artese

Svicher

Costa

et al. 2020

Drug Resistance Updates

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Coronaviridae is a peculiar viral family, with a very large RNA genome and characteristic appearance, endowed with remarkable tendency to transfer from animals to humans. Since the beginning of the 21st century, three highly transmissible and pathogenic coronaviruses have crossed the species barrier and caused deadly pneumonia, inflicting severe outbreaks and causing human health emergencies of inconceivable magnitude. Indeed, in the past two decades, two human coronaviruses emerged causing serious respiratory illness: severe acute respiratory syndrome coronavirus (SARS-CoV-1) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV), causing more than 10,000 cumulative cases, with mortality rates of 10 % for SARS-CoV-1 and 34.4 % for MERS-CoV. More recently, the severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) has emerged in China and has been identified as the etiological agent of the recent COVID-19 pandemic outbreak. It has rapidly spread throughout the world, causing nearly 22 million cases and ∼ 770,000 deaths worldwide, with an estimated mortality rate of ∼3.6 %, hence posing serious challenges for adequate and effective prevention and treatment. Currently, with the exception of the nucleotide analogue prodrug remdesivir, and despite several efforts, there is no known specific, proven, pharmacological treatment capable of efficiently and rapidly inducing viral containment and clearance of SARS-CoV-2 infection as well as no broad-spectrum drug for other human pathogenic coronaviruses. Another confounding factor is the paucity of molecular information regarding the tendency of coronaviruses to acquire drug resistance, a gap that should be filled in order to optimize the efficacy of antiviral drugs. In this light, the present review provides a systematic update on the current knowledge of the marked global efforts towards the development of antiviral strategies aimed at coping with the infection sustained by SARS-CoV-2 and other human pathogenic coronaviruses, displaying drug resistance profiles. The attention has been focused on antiviral drugs mainly targeting viral protease, RNA polymerase and spike glycoprotein, that have been tested in vitro and/or in clinical trials as well as on promising compounds proven to be active against coronaviruses by an in silico drug repurposing approach. In this respect, novel insights on compounds, identified by structure-based virtual screening on the DrugBank database endowed by multi-targeting profile, are also reported. We specifically identified 14 promising compounds characterized by a good in silico binding affinity towards, at least, two of the four studied targets (viral and host proteins). Among which, ceftolozane and NADH showed the best multi-targeting profile, thus potentially reducing the emergence of resistant virus strains. We also focused on potentially novel pharmacological targets for the development of compounds with anti-pan coronavi...

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“…The novel coronavirus, SARS-CoV-2, causing coronavirus disease 2019 (COVID-19) is a major health threat that was declared a global pandemic by the World Health Organization (WHO) in March 2020 [1][2][3]. Since the outbreak in December 2019, many people have suffered from a severe acute respiratory infection that causes respiratory failure, the need for intubation, and prolonged mechanical ventilation [4].…”

Section: Introductionmentioning

confidence: 99%

Statins in Patients with COVID-19: A Retrospective Cohort Study in Iranian COVID-19 Patients

Peymani

Dehesh

Aligolighasemabadi

et al. 2020

Preprint

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Background: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is spreading at an alarming rate globally. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and many known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. Results: After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR=0.85, 95% CI=(0.02, 3.93), P=0.762] and lower risk of death [(HR= 0.76; 95% CI=(0.16, 3.72), P=0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR=0.96, 95% CI=(0.61–2.99), P=0.942] and patients on statins had a more normal computed tomography (CT) scan result [OR=0.41, 95% CI= (0.07–2.33), P=0.312]. Conclusions: Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19 , we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.

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FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy

Cited by 132 publications

References 129 publications

Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations

Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations

Current status of antivirals and druggable targets of SARS CoV-2 and other human pathogenic coronaviruses

Statins in Patients with COVID-19: A Retrospective Cohort Study in Iranian COVID-19 Patients

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