Inhaled interferons beta and SARS-COV2 infection: a preliminary therapeutic perspective

Cojocaru, Elena; Cojocaru, Cristian; Antoniu, Sabina A; Stafie, Celina Silvia; Râjnoveanu, Armand; Râjnoveanu, Ruxandra-Mioara

doi:10.1080/17476348.2022.2008910

Cited by 4 publications

(3 citation statements)

References 35 publications

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“…Typical clinical manifestations in the first reports of SARS-CoV-2 (including fever, fatigue, loss of smell, myalgia, headache, cough and shortness of breath), have either become less significant or associated with specific variants (49)(50)(51)(52)(53). During SARS-CoV-2 infection, interferon pathways become impaired, causing higher mortality and longer disease course (54).…”

Section: Discussionmentioning

confidence: 99%

Clinical challenges of SARS‑CoV‑2 variants (Review)

Cojocaru

Turcanu

et al. 2022

Exp Ther Med

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Since the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there have been challenges recognizing the clinical features of SARS-CoV-2 and identifying therapeutic options. This has been compounded by viral mutations that affect clinical response and primary epidemiological indicators. Multiple variants of SARS-CoV-2 have been identified and classified on the basis of nomenclature implemented by scientific organizations and the World Health Organisation (WHO). A total of five variants of concern (VOCs) have been identified to date. The present study aimed to analyse clinical and epidemiological features of each variant. Based on these characteristics, predictions were made about potential future evolution. Considering the time and location of SARS-CoV-2 VOC emergence, it was hypothesised that mutations were not due to pressure caused by the vaccines introduced in December 2020 but were dependent on natural characteristics of the virus. In the process of adapting to the human body, SARS-CoV-2 is expected to undergo evolution to become more contagious but less deadly. SARS-CoV-2 was hypothesized to continue spread through isolated epidemic outbreaks due to the unimmunized population, mostly unvaccinated children and adults, and for coronaviruses to continue to present a public health problem. Contents 1. Introduction 2. SARS-CoV-2 variant gene mutations and impact of clinical features on disease evolution 3. Discussion 4. Limitations

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Section: Discussionmentioning

confidence: 99%

Clinical challenges of SARS‑CoV‑2 variants (Review)

Cojocaru

Turcanu

et al. 2022

Exp Ther Med

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“…Inhaled IFN-β tend to suppress RV load in sputum, whereas it boosted innate immunity as assessed by blood and sputum anti-viral biomarkers such as OAS1 and Mx1 ( 121 ). The effect of inhaled IFN-β on COVID19 has also been investigated ( 122 ), and available data from a phase II study demonstrate that inhaled IFN-β can accelerate recovery from the disease.…”

Section: Possible Treatment Strategies For Suppressing Viral Infectio...mentioning

confidence: 99%

Innate Immune Responses by Respiratory Viruses, Including Rhinovirus, During Asthma Exacerbation

Nakagome

Nagata

2022

Front. Immunol.

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Viral infection, especially with rhinovirus (RV), is a major cause of asthma exacerbation. The production of anti-viral cytokines such as interferon (IFN)-β and IFN-α from epithelial cells or dendritic cells is lower in patients with asthma or those with high IgE, which can contribute to viral-induced exacerbated disease in these patients. As for virus-related factors, RV species C (RV-C) induces more exacerbated disease than other RVs, including RV-B. Neutrophils activated by viral infection can induce eosinophilic airway inflammation through different mechanisms. Furthermore, virus-induced or virus-related proteins can directly activate eosinophils. For example, CXCL10, which is upregulated during viral infection, activates eosinophils in vitro. The role of innate immune responses, especially type-2 innate lymphoid cells (ILC2) and epithelial cell-related cytokines including IL-33, IL-25, and thymic stromal lymphopoietin (TSLP), in the development of viral-induced airway inflammation has recently been established. For example, RV infection induces the expression of IL-33 or IL-25, or increases the ratio of ILC2 in the asthmatic airway, which is correlated with the severity of exacerbation. A mouse model has further demonstrated that virus-induced mucous metaplasia and ILC2 expansion are suppressed by antagonizing or deleting IL-33, IL-25, or TSLP. For treatment, IFNs including IFN-β suppress not only viral replication but also ILC2 activation in vitro. Agonists of toll-like receptor (TLR) 3 or 7 can induce IFNs, which can then suppress viral replication and ILC2 activation. Therefore, if delivered in the airway, IFNs or TLR agonists could become innovative treatments for virus-induced asthma exacerbation.

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“…With the above reference to nirmatrelvir, it is thus appropriate to look at type I IFNs in terms of their effects on treatment of COVID19 at the early stages of infection. In this regard, IFN-a2b, IFN-b-1a, and IFN-b-1b have shown promise when administered intranasally or injected early in COVID19 infections (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Disparate viral pandemics from COVID19 to monkeypox and beyond: a simple, effective and universal therapeutic approach hiding in plain sight

Johnson,

Ahmed

2023

Front. Immunol.

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The field of antiviral therapeutics is fixated on COVID19 and rightly so as the fatalities at the height of the pandemic in the United States were almost 1,000,000 in a twelve month period spanning parts of 2020/2021. A coronavirus called SARS–CoV2 is the causative virus. Development of a vaccine through molecular biology approaches with mRNA as the inducer of virus spike protein has played a major role in driving down mortality and morbidity. Antivirals have been of marginal value in established infections at the level of hospitalization. Thus, the current focus is on early symptomatic infection of about the first five days. The Pfizer drug paxlovid which is composed of nirmatrelvir, a peptidomimetic protease inhibitor of SARS–CoV2 Mpro enzyme, and ritonavir to retard degradation of nirmatrelvir, is the current FDA recommended treatment of early COVID19. There is no evidence of broad antiviral activity of paxlovid against other diverse viruses such as the influenza virus, poxviruses, as well as a host of respiratory viruses. Although type I interferons (IFNs) are effective against SARS–CoV2 in cell cultures and in early COVID19 infections, they have not been broadly recommended as therapeutics for COVID19. We have developed stable peptidomimetics of both types I and II IFNs based on our noncanonical model of IFN signaling involving the C-terminus of the IFNs. We have also identified two members of intracellular checkpoint inhibitors called suppressors of cytokine signaling (SOCS), SOCS1 and SOCS3 (SOCS1/3), and shown that they are virus induced intrinsic virulence proteins with activity against IFN signaling enzymes JAK2 and TYK2. We developed a peptidomimetic antagonist, based on JAK2 activation loop, against SOCS1/3 and showed that it synergizes with the IFN mimetics for potent broad spectrum antiviral activity without the toxicity of intact IFN molecules. IFN mimetics and the SOCS1/3 antagonist should have an advantage over currently used antivirals in terms of safety and potency against a broad spectrum of viruses.

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Inhaled interferons beta and SARS-COV2 infection: a preliminary therapeutic perspective

Cited by 4 publications

References 35 publications

Clinical challenges of SARS‑CoV‑2 variants (Review)

Clinical challenges of SARS‑CoV‑2 variants (Review)

Innate Immune Responses by Respiratory Viruses, Including Rhinovirus, During Asthma Exacerbation

Disparate viral pandemics from COVID19 to monkeypox and beyond: a simple, effective and universal therapeutic approach hiding in plain sight

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