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    Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection
    (MDPI, 2020-01-01) Palmeira, Andreia; Sousa, Emilia; Koseler, Aylin; Sabirli, Ramazan; Goren, Tarik; Turkcuer, Ibrahim; Kurt, Ozgur; Pinto, Madalena M.; Helena Vasconcelos, M.
    SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (-) pneumonia patients. In addition, we aimed to identify drugs that could be repurposed to inhibit GRP78, thus with potential anti-SARS-CoV-2 activity. Gene expression studies were performed in 10 SARS-CoV-2 (-) and 24 SARS-CoV-2 (+) pneumonia patients. A structure-based virtual screen was performed with 10,761 small molecules retrieved from DrugBank, using the GRP78 nucleotide binding domain and substrate binding domain as molecular targets. Results indicated that GRP78 mRNA levels were approximately four times higher in the blood of SARS-CoV-2 (+) versus SARS-CoV-2 (-) pneumonia patients, further suggesting that GRP78 might be a good molecular target to treat Covid-19. In addition, a total of 409 compounds were identified with potential as GRP78 inhibitors. In conclusion, we found preliminary evidence that further proposes GRP78 as a possible molecular target to treat Covid-19 and that many clinically approved drugs bind GRP78 as an off-target effect. We suggest that further work should be urgently carried out to confirm if GRP78 is indeed a good molecular target and if some of those drugs have potential to be repurposed for SARS-CoV-2 antiviral activity.
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    Endoplasmic Reticulum Stress Markers in SARS-COV-2 Infection and Pneumonia: Case-Control Study
    (INT INST ANTICANCER RESEARCH, 2020-01-01) Koseler, Aylin; Sabirli, Ramazan; Goren, Tarik; Turkcuer, Ibrahim; Kurt, Ozgur
    Background/Aim: A novel human coronavirus, named SARS-COV-2, has recently caused thousands of deaths all around the world. Endoplasmic reticulum (ER) stress plays an important role in the development of diseases. Patients and Methods: We aimed to to investigate the relationship between ER stress markers in patients infected with SARS-COV-2 and patients with pneumonia. A total of 9 patients (4 patients diagnosed with pneumonia and 5 patients diagnosed with SARS-COV-2 infection) who admitted to the emergency Department with symptoms of pneumonia and SARS-COV-2 were included in the study. A total of 18 healthy individuals without any known chronic or acute disease and drug use were included as the healthy control group. Serum human glucose regulated protein 78 (GRP78), serum human C/EBP homologous protein (CHOP) and serum human phospho extracellular signal regulated kinase (PERK) levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: GRP78 levels were found to be significantly higher in SARS-COV-2 positive cases compared to individuals in other groups. Serum GRP78 level median value was statistically significantly higher in SARS-COV-2-positive group compared to the other groups (p=0.0003). Serum PERK level was statistically significantly higher in SARS-COV-2-positive pneumonia cases (p=0.046). Conclusion: An association was shown between GRP78 and SARS-COV-2 infection. Although a small number of patients was investigated, these results will be important and guide future treatments of SARS-COV-2.
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    High GRP78 levels in Covid-19 infection: A case-control study
    (PERGAMON-ELSEVIER SCIENCE LTD, 2021-01-01) Sabirli, Ramazan; Koseler, Aylin; Goren, Tarik; Turkcuer, Ibrahim; Kurt, Ozgur
    Introduction: Covid-19 infection was declared a global pandemic by WHO on March 11, 2020. GRP78 protein is known to be involved in the intrusion of numerous viruses. Our current study tries to provide some insight into the variation of GRP78 protein levels in patients with Covid-19 (-) pneumonia, Covid-19 (+) pneumonia, and CT negative Covid-19 infection in comparison to the normal population through a larger number of cases. Materials and methods: 42 patients who have Covid-19 (-) pneumonia