Blocking Egfr with Nimotuzumab: A Novel Strategy for Covid-19 Treatment

Londres, Henrry Diaz; Armada, Jorge Jiménez; Martínez, Aray Hernández; Abdo-Cuza, Anselmo; Sánchez, Yamilka Hernández; Rodríguez, Aylin Granado; Figueroa, Sarahy Sepúlveda; Gregorich, Egda M Llanez; Lahera, Mery L Torres; Peire, Francisco Gómez; Montero-González, Teresita; González, Yaneth Zamora; Añé-Kourí, Ana Laura; Palomo, Addys González; Concepción, Mayelin Troche; Pérez, Loipa Medel; Luaces-Alvarez, Patricia Lorenzo; Iglesias, Daymys Estévez; Saavedra, Danay; Ramos-Suzarte, Mayra; Ramos, Tania Crombet

doi:10.2217/imt-2022-0027

Cited by 21 publications

(35 citation statements)

References 42 publications

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“…4). The most significantly associated predicted upstream regulator is EGFR, which has been implicated as a potential therapeutic target for COVID-19 treatment (Klann et al, 2020; Londres et al, 2022; Vagapova et al, 2021; Venkataraman and Frieman, 2017). Other predicted upstream regulators with known function in inflammation and innate immunity include mitogen-activated protein kinase kinase 7 (MAP2K7), tumor necrosis factor receptor superfamily member 1A (TNFRSF1A), sprouty RTK signaling antagonist 4 (SPRY4), Janus kinase 3 (JAK3), Janus kinase 2 (JAK2), interferon alpha 1 (IFNA1), and tumor necrosis factor (TNF).…”

Section: Resultsmentioning

confidence: 99%

Epitranscriptomic N⁶-methyladenosine profile of SARS-CoV-2-infected human lung epithelial cells

Phillips

Khadka

Bohan

et al. 2022

Preprint

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N6-methyladenosine (m6A) is a dynamic post-transcriptional RNA modification that plays an important role in determining transcript fate. Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused the global pandemic of coronavirus disease 2019 (COVID-19) and the virus has been extensively studied. However, how m6A modification of host cell RNAs change during SARS-CoV-2 infection has not been reported. Here we define the epitranscriptomic m6A profile of SARS-CoV-2-infected human lung epithelial cells compared to uninfected controls. Biological pathway analyses revealed that differentially methylated transcripts were significantly associated with cancer-related pathways, protein processing in the endoplasmic reticulum, cell death and proliferation. Upstream regulators predicted to be associated with the proteins encoded by differentially methylated mRNAs include proteins involved in the type I interferon response, inflammation, and cytokine signaling. These data suggest that m6A modification of cellular RNA is an important mechanism of regulating host gene expression during SARS-CoV-2 infection of lung epithelial cells.

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Section: Resultsmentioning

confidence: 99%

Epitranscriptomic N⁶-methyladenosine profile of SARS-CoV-2-infected human lung epithelial cells

Phillips

Khadka

Bohan

et al. 2022

Preprint

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“…Moreover, the use of EGFR inhibitors in the setting of COVID-19 can be controversial, due to the previous reports of interstitial lung disease in patients with lung adenocarcinoma treated with EGFR tyrosine kinase inhibitors (27). The first clinical trial in hospitalized COVID-19 patients, demonstrated that nimotuzumab was very safe and the 14-day recovery rate was 82.9% (9). Only 8 patients (19.5%) of 41 required invasive mechanical ventilation.…”

Section: Discussionmentioning

confidence: 99%

“…After 7 days, 76.2% of the subjects with a severe condition, improved the PO2/FiO2 ratio and there was a significant reduction of the affected lung areas. Inflammatory markers including C-reactive protein, ferritin, lactate dehydrogenase (LDH), neutrophil to lymphocyte ratio (NLR), D-dimer, interleukin 6 and plasminogen activator inhibitor-1 (PAI-1) decreased over time (9). This manuscript reports for the first time the safety and recovery rate of patients treated with an anti-EGFR drug plus the standard of care vs. the standard of care alone, in a relatively large population in the conditions of the usual medical practice.…”

Section: Discussionmentioning

confidence: 99%

“…Recovery rate was 80.64% in severe patients. Inflammatory markers decreased overtime and interleukin-6 concentration diminished from 46.5-14.51 pg/ml at day 7 (9).…”

Section: Introductionmentioning

confidence: 95%

“…The blockade of EGFR emerges as a novel strategy for COVID-19 patients, provided its role in inflammation, immunethrombosis and fibrosis (8,9). Nimotuzumab is a humanized anti-EGFR monoclonal antibody, which is approved for the treatment of several epithelial tumors (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

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Nimotuzumab Increases the Recovery Rate of Severe and Critical COVID-19 Patients: Evaluation in the Real-World Scenario

Diaz

J²,

Hernández

et al. 2022

Front. Public Health

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EGFR signaling is an important regulator of SARS-CoV induced lung damage, inflammation and fibrosis. Nimotuzumab is a humanized anti-EGFR antibody registered for several cancer indications. An expanded access study was conducted to evaluate the safety and recovery rate of severe and critical patients with confirmed SARS-CoV-2 infection, treated with nimotuzumab in combination with the standard of care in the real-world scenario. The antibody was administered as an intravenous infusions every 72 h, up to 5 doses. In order to assess the impact of nimotuzumab, the recovery rate was compared with a paired retrospective cohort. Control patients received standard treatment according the national protocol but not nimotuzumab. Overall, 1,151 severe or critical patients received nimotuzumab in 21 hospitals of Cuba. Median age was 65 and 773 patients had at least one comorbidity. Nimotuzumab was very well-tolerated and mild or moderate adverse events were detected in 19 patients. 1,009 controls matching with the nimotuzumab patients, were selected using a “propensity score” method. The 14-day recovery rate of the nimotuzumab cohort was 72 vs. 42% in the control group. Controls had a higher mortality risk (RR 2.08, 95% CI: 1.79, 2.38) than the nimotuzumab treated patients. The attributable fraction was 0.52 (95% CI: 0.44%; 0.58), and indicates the proportion of deaths that were prevented with nimotuzumab. Our preliminary results suggest that nimotuzumab is a safe antibody that can reduce the mortality of severe and critical COVID-19 patients.

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Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS‐CoV‐2

Xue

Mei

Chen

et al. 2023

MedComm

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The coronavirus disease 2019 (COVID‐19) pandemic has affected a large portion of the global population, both physically and mentally. Current evidence suggests that the rapidly evolving coronavirus subvariants risk rendering vaccines and antibodies ineffective due to their potential to evade existing immunity, with enhanced transmission activity and higher reinfection rates that could lead to new outbreaks across the globe. The goal of viral management is to disrupt the viral life cycle as well as to relieve severe symptoms such as lung damage, cytokine storm, and organ failure. In the fight against viruses, the combination of viral genome sequencing, elucidation of the structure of viral proteins, and identifying proteins that are highly conserved across multiple coronaviruses has revealed many potential molecular targets. In addition, the time‐ and cost‐effective repurposing of preexisting antiviral drugs or approved/clinical drugs for these targets offers considerable clinical advantages for COVID‐19 patients. This review provides a comprehensive overview of various identified pathogenic targets and pathways as well as corresponding repurposed approved/clinical drugs and their potential against COVID‐19. These findings provide new insight into the discovery of novel therapeutic strategies that could be applied to the control of disease symptoms emanating from evolving SARS‐CoV‐2 variants.

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Blocking Egfr with Nimotuzumab: A Novel Strategy for Covid-19 Treatment

Cited by 21 publications

References 42 publications

Epitranscriptomic N⁶-methyladenosine profile of SARS-CoV-2-infected human lung epithelial cells

Epitranscriptomic N⁶-methyladenosine profile of SARS-CoV-2-infected human lung epithelial cells

Nimotuzumab Increases the Recovery Rate of Severe and Critical COVID-19 Patients: Evaluation in the Real-World Scenario

Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS‐CoV‐2

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Blocking Egfr with Nimotuzumab: A Novel Strategy for Covid-19 Treatment

Cited by 21 publications

References 42 publications

Epitranscriptomic N6-methyladenosine profile of SARS-CoV-2-infected human lung epithelial cells

Epitranscriptomic N6-methyladenosine profile of SARS-CoV-2-infected human lung epithelial cells

Nimotuzumab Increases the Recovery Rate of Severe and Critical COVID-19 Patients: Evaluation in the Real-World Scenario

Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS‐CoV‐2

Contact Info

Product

Resources

About

Epitranscriptomic N⁶-methyladenosine profile of SARS-CoV-2-infected human lung epithelial cells

Epitranscriptomic N⁶-methyladenosine profile of SARS-CoV-2-infected human lung epithelial cells