New hope for treatment of respiratory involvement following COVID-19 by bromhexine

Barzegar, Abdolrazagh; Ghadipasha, Masoud; Rezaei, Nima; Forouzesh, Mehdi; Valizadeh, Rohollah

doi:10.34172/npj.2021.11

Cited by 25 publications

(13 citation statements)

References 12 publications

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“…3,4 Researchers have proposed that bromhexine may be an effective option to reduce primary transmission, viral load, dissemination and secondary replication of SARS-CoV-2. [5][6][7][8] COVID-19, like SARS-CoV, binds to human ACE 2 via its spike glycoprotein (S-protein) expressed on its envelope for entering the target cell. S protein is composed of one amino-terminal (S1) and one carboxyterminal (S2).…”

Section: Introductionmentioning

confidence: 99%

Effect of bromhexine in hospitalized patients with COVID-19

Tolouian¹,

Mulla²,

Jamaati³

et al. 2023

Journal of Investigative Medicine

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BackgroundBromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection; however, its efficacy in COVID-19 is controversial.MethodsA group of hospitalized patients with confirmed COVID-19 pneumonia were randomized using 1:1 allocation to either standard treatment lopinavir/ritonavir and interferon beta-1a or bromhexine 8 mg four times a day in addition to standard therapy. The primary outcome was clinical improvement within 28 days, and the secondary outcome measures were time to hospital discharge, all-cause mortality, duration of mechanical ventilation, the temporal trend in 2019-nCoV reverse transcription-polymerase chain reaction positivity and the frequency of adverse drug events within 28 days from the start of medication.ResultsA total of 111 patients were enrolled in this randomized clinical trial and data from 100 patients (48 patients in the treatment arm and 52 patients in the control arm) were analyzed. There was no significant difference in the primary outcome of this study, which was clinical improvement. There was no significant difference in the average time to hospital discharge between the two arms. There were also no differences observed in the mean intensive care unit stay, frequency of intermittent mandatory ventilation, duration of supplemental oxygenation or risk of death by day 28 noted between the two arms.ConclusionBromhexine is not an effective treatment for hospitalized patients with COVID-19. The potential prevention benefits of bromhexine in asymptomatic postexposure or with mild infection managed in the community remain to be determined.

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Section: Introductionmentioning

confidence: 99%

Effect of bromhexine in hospitalized patients with COVID-19

Tolouian¹,

Mulla²,

Jamaati³

et al. 2023

Journal of Investigative Medicine

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“…It should be known that macro-level health policies such as vaccination, social distancing, new trials about pharmaceutical agents and other preventive measures are strongly needed to prevent patients from severe forms of COVID-19 involving lung damage. We believe that prophylaxis is better than diagnosis and treatment (19)(20)(21). However, our study had some limitations.…”

mentioning

confidence: 88%

Evaluation of the Sensitivity of Prominent Biomarkers Involvement in Diagnosing the Severity of Lung Damage in Patients with COVID-19

Khodadadi

Khodakarim

Kalantari

et al. 2023

MJIRI

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Background: COVID-19 has become the greatest pandemic of the century. Considering the role of some hematologic and biochemical factors and their alterations due to the activity of the immune system, the current study aimed to evaluate LDH/CRP/ESR/RDW in patients with COVID-19 and their relationship with the severity of lung involvement based on CT scan findings.Methods: In this cross-sectional study, some biomarkers (LDH/CRP/ESR/RDW) were measured in 158 patients who were admitted to the intensive care unit (ICU) or hospitalized in the infectious diseases ward of Rasoul-e-Akram and Firoozgar hospitals or attended to the outpatient clinics. The diagnosis was confirmed by a positive RT-PCR test in all patients. The severity of lung involvement was determined by CT scan findings for comparison. Data were collected and analyzed through SPSS version 22.Results: Regarding the severity of lung damage according to the CT scan, 17.7% of the patients were normal, 19% had less than 25% involvement, 17% had 25% -50% involvement, 33.5% had 50% -75% involvement, and 12% had more than 75% involvement. Considering the increasing severity of lung damage based on CT scans, the levels of RDW, ESR, CRP, and LDH significantly increased in parallel.

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“…Bromhexine hydrochloride (BRH) is a TMPRSS2 inhibitor that can attenuate metastasis in prostate cancer mice models (Lucas et al, 2014). Being an FDA-approved drug in mucolytic cough suppressants with no significant adverse effects, it can effectively be used against coronavirus infections (Barzegar et al, 2020;Wang et al, 2020c;Fu et al, 2020;Tolouian et al, 2020). In this regard, Li et al conducted a clinical pilot study on Chinese patients to evaluate the beneficial effects of BRH tablets in moderate COVID-19 treatment.…”

Section: Modulating the Expression And Activity Of Tmprss2mentioning

confidence: 99%

Host Serine Proteases: A Potential Targeted Therapy for COVID-19 and Influenza

Saadat

Khatibi

Vahed

et al. 2021

Front. Mol. Biosci.

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The ongoing pandemic illustrates limited therapeutic options for controlling SARS-CoV-2 infections, calling a need for additional therapeutic targets. The viral spike S glycoprotein binds to the human receptor angiotensin-converting enzyme 2 (ACE2) and then is activated by the host proteases. Based on the accessibility of the cellular proteases needed for SARS-S activation, SARS-CoV-2 entrance and activation can be mediated by endosomal (such as cathepsin L) and non-endosomal pathways. Evidence indicates that in the non-endosomal pathway, the viral S protein is cleaved by the furin enzyme in infected host cells. To help the virus enter efficiently, the S protein is further activated by the serine protease 2 (TMPRSS2), provided that the S has been cleaved by furin previously. In this review, important roles for host proteases within host cells will be outlined in SARS-CoV-2 infection and antiviral therapeutic strategies will be highlighted. Although there are at least five highly effective vaccines at this time, the appearance of the new viral mutations demands the development of therapeutic agents. Targeted inhibition of host proteases can be used as a therapeutic approach for viral infection.

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New hope for treatment of respiratory involvement following COVID-19 by bromhexine

Cited by 25 publications

References 12 publications

Effect of bromhexine in hospitalized patients with COVID-19

Effect of bromhexine in hospitalized patients with COVID-19

Evaluation of the Sensitivity of Prominent Biomarkers Involvement in Diagnosing the Severity of Lung Damage in Patients with COVID-19

Host Serine Proteases: A Potential Targeted Therapy for COVID-19 and Influenza

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