Effects of 5‐alpha reductase inhibitors on lung function: A reason for discontinuation during<scp>COVID</scp>‐19 pandemic?

Kroumpouzos, George

doi:10.1111/dth.13535

Cited by 6 publications

(8 citation statements)

References 10 publications

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“… Yes Kroumpouzos, George. [84] Chernyshev, Anatoly. [79] Hosseini, Maryam, et al [78] 19 BPH Doxazosin (DB00590) alpha-1 antagonist treat benign prostatic hypertrophy potential SARS-CoV-2 Mpro inhibitor (validated by MD trajectory clustering) Yes Gupta, Aayush [80] 20 Impotency Tadalafil (DB00820) PDE5 inhibitor treat erectile dysfunction Potential against nsp1 (DeepDTA method) 2’-O-methyltransferase potential inhibitor Yes Anwar, Muhamma [114] Sharma, [81] 21 Anti psychotic Fluspirilene (DB04842) Neurotransmitter inhibitor Used for chronic schizophrenia An antagonist for Dopamine D2 receptor and 5-HT receptor 2 A Inhibits Voltage-dependent calcium channel gamma-1 Active against SARS-CoV-2 in-vitro in Vero E6 cell line Activity against SARS-CoV and MERS-CoV in-vitro Vero E6 cell line Weston S. et al [115] Dyall J. et al [116] 22 Anti psychotic Pimozide (DB01100) Diphenylbutylpiperidine Suppress vocal and motor tics in Tourette syndrome An antagonist of Dopamine D2, D3 receptor Inhibits Potassium voltage-gated channel subfamily H member two and Calmodulin Binding affinity against 3C-like protease Is expected to raise endosomal pH.…”

Section: Resultsmentioning

confidence: 99%

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Identification of FDA approved drugs against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and 3-chymotrypsin-like protease (3CLpro), drug repurposing approach

Molavi

Razi

Mirmotalebisohi

et al. 2021

Biomedicine & Pharmacotherapy

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The RNA-dependent RNA polymerase (RdRp) and 3C-like protease (3CLpro) from SARS-CoV-2 play crucial roles in the viral life cycle and are considered the most promising targets for drug discovery against SARS-CoV-2. In this study, FDA-approved drugs were screened to identify the probable anti-RdRp and 3CLpro inhibitors by molecular docking approach. The number of ligands selected from the PubChem database of NCBI for screening was 1760. Ligands were energy minimized using Open Babel. The RdRp and 3CLpro protein sequences were retrieved from the NCBI database. For Homology Modeling predictions, we used the Swiss model server. Their structure was then energetically minimized using SPDB viewer software and visualized in the CHIMERA UCSF software. Molecular dockings were performed using AutoDock Vina, and candidate drugs were selected based on binding affinity (∆G). Hydrogen bonding and hydrophobic interactions between ligands and proteins were visualized using Ligplot and the Discovery Studio Visualizer v3.0 software. Our results showed 58 drugs against RdRp, which had binding energy of -8.5 or less, and 69 drugs to inhibit the 3CLpro enzyme with a binding energy of -8.1 or less. Six drugs based on binding energy and number of hydrogen bonds were chosen for the next step of molecular dynamics (MD) simulations to investigate drug-protein interactions (including Nilotinib, Imatinib and dihydroergotamine for 3clpro and Lapatinib, Dexasone and Relategravir for RdRp). Except for Lapatinib, other drugs-complexes were stable during MD simulation. Raltegravir, an anti-HIV drug, was observed to be the best compound against RdRp based on docking binding energy (-9.5 kcal/mole) and MD results. According to the MD results and binding energy, dihydroergotamine is a suitable candidate for 3clpro inhibition (−9.6 kcal/mol). These drugs were classified into several categories, including antiviral, antibacterial, anti-inflammatory, anti-allergic, cardiovascular, anticoagulant, BPH and impotence, antipsychotic, antimigraine, anticancer, and so on. The common prescription-indications for some of these medication categories appeared somewhat in line with manifestations of COVID-19. We hope that they can be beneficial for patients with certain specific symptoms of SARS-CoV-2 infection, but they can also probably inhibit viral enzymes. We recommend further experimental evaluations in vitro and in vivo on these FDA-approved drugs to assess their potential antiviral effect on SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

“…Based on these reasons, an androgen antagonist like Dutasteride could be a therapeutically beneficial drug for COVID-19. However, some cautions should be considered, and more preclinical studies seem to be required since inhibition of 5-AR impair the regeneration capacity of the respiratory epithelium [84] .…”

Section: Discussionmentioning

confidence: 99%

Identification of FDA approved drugs against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and 3-chymotrypsin-like protease (3CLpro), drug repurposing approach

Molavi

Razi

Mirmotalebisohi

et al. 2021

Biomedicine & Pharmacotherapy

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“…Research to date has not yet clearly determined the reason for differences of COVID-19 infection severity and outcome between adult females and males. This issue was discussed theoretically in 4 earlier studies ( 5 - 8 ). These studies have introduced the hypothesis that finasteride has a beneficial or harm effect on clinical outcomes in adults with COVID-19 pneumonia.…”

Section: Introductionmentioning

confidence: 88%

Finasteride in hospitalized adult males with COVID-19: A risk factor for severity of the disease or an adjunct treatment: A randomized controlled clinical trial

Zarehoseinzade

Allami

Ahmadi³

et al. 2021

mjiri

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Background: There is controversy about the efficacy of 5-alpha-reductase inhibitors in COVID-19 patients. Some assumed that finasteride might be a risk factor for deterioration and others proposed it as a possible adjunct treatment for moderate to severe COVID-19 infection in the elderly. Methods: We performed a randomized controlled clinical trial (registration ID IRCT20200505047318N1) on 80 hospitalized male patients aged ≥50 years diagnosed with COVID-19 pneumonia in a tertiary hospital in Qazvin (Iran) from April to July 2020. The patients were randomized into one of the 2 treatment groups using simple randomization. Treatment group patients underwent routine drug therapy and 5 mg finasteride once daily for 7 days. The primary endpoint was mortality rate and length of hospital stay (LOS), and secondary endpoints were peripheral capillary oxygen saturation, respiratory rate, and inflammatory markers changes. The study protocol was approved by the medical ethics committee of Qazvin University of Medical Sciences (registration ID IR.QUMS.REC.1399.080). Data were analyzed by statistical tests and SPSS version 25. Also, p<0.05 was considered to be statistically significant. Results: We found a significant difference on O2 saturation among the 2 study groups on fifth day compared with the admission time (p= 0.018). The results did not show significant differences in mortality rate (2.5% vs 10%; p= 0.166) and LOS (p= 0.866) between patients in the finasteride and the control group. Conclusion: A short course of finasteride administration partially improves O2 saturation but does not influence other outcomes in hospitalized male patients aged ≥50 years with COVID-19 pneumonia. Further research in a large scale with longer follow-up is required to help clarify the role of finasteride in this setting.

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“…Therefore, 5-ARIs may negatively affect such functions by disrupting androgen metabolism [21]. However, further studies are still needed to assess whether a discontinuation of 5-alpha-reductase inhibitors may be beneficial for patients who tested positive for SARS-CoV-2, especially for those at high risk for the disease [22]. Conversely, some studies suggest that men chronically exposed to 5-ARIs may be less vulnerable to severe COVID-19 [23], and 5-ARIs may reduce viral shedding, inflammatory response, and time to remission.…”

Section: Medical Treatments For Luts Due To Bpe and Covid-19mentioning

confidence: 99%

Management of Men With Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia During and After COVID-19

Baard¹,

Averbeck²,

Hassouna³

et al. 2021

SIUJ

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The lower urinary tract (LUT), in particular the prostate, has been theoretically recognized as a target for SARS-CoV-2. Moreover, common pathophysiological mechanisms have been described for BPE/LUTS and COVID-19, including RAS dysregulation, androgen receptors, and MetS-related factors. These factors raise concerns about the possibility of worse urological outcomes due to BPE/LUTS progression in COVID-19 patients. The available results suggest a correlation between SARS-CoV-2 infection, exacerbation or new onset of LUTS, and semen impairment. BPE patients’ care and management have been deeply affected by COVID-19. In the midst of the pandemic, the main urological guidelines suggested postponement of BPH-related deferrable medical examinations and surgery. Telemedicine, therefore, gained attention and interest. Clinical evidence of impaired QoL or complications expedited surgical intervention. An informed consent covering the risk of COVID-19 and a negative molecular PCR within 72 hours of surgery were mandatory. A reduction in procedures under general anaesthesia was recommended. Long waiting lists accrued worldwide during the pandemic, leading to regular review of the BPE waiting lists and patients’ clinical status, encouraging the increase of minimally invasive office-based procedures, even in the post-COVID-19 era, and the improvement of telemedicine. Prospective studies are still needed to assess the course of LUTS/BPE patients after COVID-19.

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Effects of 5‐alpha reductase inhibitors on lung function: A reason for discontinuation duringCOVID‐19 pandemic?

Abstract: Goren and colleagues have written an informative article on how androgens may be implicated in coronavirus disease 2019 (COVID-CONFLICT OF INTEREST The author declares no conflict of interest.

Cited by 6 publications

References 10 publications

Identification of FDA approved drugs against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and 3-chymotrypsin-like protease (3CLpro), drug repurposing approach

Identification of FDA approved drugs against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and 3-chymotrypsin-like protease (3CLpro), drug repurposing approach

Finasteride in hospitalized adult males with COVID-19: A risk factor for severity of the disease or an adjunct treatment: A randomized controlled clinical trial

Management of Men With Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia During and After COVID-19

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