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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.

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 GRP-78 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.Coronaviruses are spherical or pleomorphic in shape with a mean diameter of 80-120 nm. They have heavily glycosylated trimeric spike (S) proteins on their surface (1). Coronavirus infection starts with receptor binding via the S protein. The interaction between the host cell surface receptor and the S1 subunit is the major determinant of the tropism of coronaviruses (2, 3). Upon receptor binding of S1, a conformational change is triggered in the S2 subunit, exposing its hidden fusion peptide for insertion into the cellular membrane.Endoplasmic reticulum (ER) is the organelle where the synthesis, folding, maturation and transport of proteins, calcium storage and lipid biosynthesis of the cell processes take place. ER stress is defined as the result of ER protein folding capacity, resulting in wrongly folded or unfolded protein accumulation (4). Excessive synthesis of secretion proteins, mutations in proteins involved in protein folding, abnormal changes in the amount of Ca +2 in ER and viral infections are some of the factors that cause protein accumulation in ER (5,6). The cell activates three mechanisms to eliminate ER stress caused by an imbalance between the amount of unfolded proteins in ER and the capacity of the cellular mechanism that handles this amount. Firstly, protein synthesis and translocation of proteins to ER are decreased, and the amount of protein entering ER is reduced with a temporary adaptation. Secondly; unfolded protein response (UPR) is activated. Therefore, an increase in the ca...

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Introduction To our knowledge, the diagnostic value of the sP-Selectin level in the diagnosis of COVID-19 disease has not yet been investigated. In this study, we aimed to assess this by evaluating the relationship between sP-Selectin level and the clinical severity of COVID-19 infections. Methods A total of 80 patients (50 with mild to moderate and 30 with severe COVID-19 pneumonia), and 60 non-symptomatic healthy volunteers participated in the study. Following serum isolation, sP-Selectin levels were assessed by Enzyme-Linked Immunosorbent Assay (ELISA) method. Results The serum sP-Selectin level was 1.7 ng/ml in the control group (1–3.78); 6.24 ng/ml (5.14–7.23) in mild-to-moderate pneumonia group; and 6.72 ng/ml (5.36–8.03) in the severe pneumonia group. Serum sP-Selectin levels in both mild-to-moderate pneumonia and severe pneumonia groups were found to be higher than the control group, with statistical significance ( p = 0.0001 and p = 0.0001, respectively). Receiver operating characteristic analysis (ROC) showed greater area under the curve (AUC) for the serum sP-Selectin levels of the COVID-19 patients (AUC = 0.913, 95% CI = 0.857–0.969; p = 0.0001). The serum sP-Selectin level was found to be 97.5% sensitive and 80% specific at 4.125 ng/ml level for diagnosis (p = 0.0001). The serum sP-Selectin level was found to be 76.9% sensitive and 51.9% specific at the level of 6.12 ng/ml ( p = 0.005) to predict the need for intensive care treatment. Conclusion This study showed that sP-Selectin can be used as a valuable biomarker in both diagnosing and predicting the need for intensive care treatment of COVID-19 infection.

Hb D-Los Angeles (also known as D-Punjab, D-North Carolina, D-Portugal, D-Chicago and Oak Ridge) is an abnormal hemoglobin (Hb) with an amino acid substitution of glutamine for glutamic acid at codon 121 of the beta-globin gene. The origin and spread of Hb D-Los Angeles is not known. This is due to lack of information and remains to be elucidated. According to published reports, the Hb D-Los Angeles mutation is mostly linked with Mediterranean haplotype I [+ - - - - + +]. Besides the Mediterranean haplotype, a novel haplotype was also reported from Thailand [- - + + - - + + +]. Here we report a new haplotype from Turkey [- + -- + + +] that has not been described before. These results suggest that the Hb D-Los Angeles mutation has at least three different genetic origins.

Background/Aim: Extracellular S100b effects are mediated by the receptor for advanced glycation end products (RAGE), which is the S100b membrane receptor. RAGE belongs to the immunoglobulin superfamily of cell surface molecules and serves as a multiligand receptor and is expressed in high abundance by alveolar type I (AT-I) cells in adult pulmonary tissue. This study aimed to provide an insight into the association between the severity of COVID-19 disease and serum S100b levels during admission to the emergency department (ED). Patients and Methods: A total of 64 patients (34 mild cases; 30 severe cases) were diagnosed with COVID-19 pneumonia and 30 healthy volunteers were admitted to study. Serum S100b levels were measured by using enzymle linked immunoassay method from blood serum samples. Results: Serum S100b levels showed a significantly higher mean value in mild and severe disease cohorts than in healthy controls (p=0.036 and p=0.028 respectively). Receiver operating characteristic (ROC) analysis indicated greater area under the curve (AUC) for serum S100b levels of the p=0.014). In addition, serum S100b concentration was measured as 151.7 ng/ml at 79.3% sensitivity and 51.7% specificity (p=0.014). Serum S100b protein levels can serve as a valuable clinical marker in establishing diagnosis of patients. Though not useful in identifying different stages of COVID-19 infection, serum S100b concentration along with other known markers can be utilized to reliably predict clinical severity along with other clinical parameters. Transmitted from human to human through droplets, Coronavirus disease-19 (COVID-19) infection can progress asymptomatically. Its clinical manifestations, however, have a wide spectrum in symptomatic patients, ranging from upper respiratory tract infections (URTI) to serious clinical conditions such as pneumonia, acute respiratory disease syndrome (ARDS), sepsis, and septic shock (1, 2).S100b protein is a cytosolic calcium binding biomarker with a molecular mass of 21 kDa. Despite its extra-cranial presence, S100b is mainly expressed in the central nervous system (CNS) (3). As a cytosolic calcium sensor, this protein acts on dynamics of cytoskeletal components, energy metabolism, protein phosphorylation, and calcium homeostasis. When released from damaged cells, extracellular signals could be activated by S100b. It is also structurally released by astrocytes in the brain and can function in an autocrine or paracrine manner (4).Accumulating data from in vitro experiments have revealed the impact of extracellular S100b on the biology of various cellular types other than the CNS. In vitro trials have provided clinical evidence that S100b, similar to other S100 family of proteins, stimulates inflammatory responses in lymphocytes, vascular smooth muscle cells, endothelial cells, macrophages, and cardiomyocytes (5,6).Inside and outside the CNS, S100b acts as a damaged molecular model (DAMP) protein, which is released from damaged cells and can activate cells of innate immune response, altering the ...

Background Annexin A1 (AnxA1) is an important endogenous glucocoticoid protein that contributes to the suppression of inflammation by limiting the production of neutrophil and pro‐inflammatory cytokines. This study aims to determine the clinical predictivity value of blood AnxA1 levels in patients with mild and severe–critical pneumonia induced by COVID‐19. Methods This study employed a prospective, case–control study design and was conducted at Ankara Training and Research hospital between 10 February 2021 and 15 March 2021. A total of 74 patients (42 of whom had moderate and 32 of whom had severe/critical cases of COVID‐19 disease according to World Health Organization guidelines) and 50 nonsymptomatic healthy volunteers participated in the study. Blood samples were taken from patients at the time of hospital admission, after which serum was isolated. Following the isolation of serum, AnxA1 levels were evaluated using the enzyme‐linked immunosorbent assay method. Results The serum AnxA1 levels were measured as 25.5 (18.6‐38.6) ng/ml in the control group, 21.2 (14.7‐32) ng/ml in the moderate disease group, and 14.8 (9.7‐26.8) ng/ml in the severe/critical disease group. Serum AnxA1 levels were significantly lower in the severe/critical disease group compared with the control and moderate disease groups ( P = .01 and P = .0001, respectively). Using receiver operating characteristic analysis, a larger area under the curve (AUC) for the serum AnxA1 levels of the control group (AUC = 0.715, 95% CI = 0.626‐0.803; P = .0001) was calculated compared with the COVID‐19 patient group for the diagnosis of COVID‐19 disease. The AnxA1 level was found to be 80% sensitive and 54.1% specific at a cut‐off level of 18.5 ng/ml for the diagnosis of COVID‐19 disease. Moreover, the AnxA1 level was found to be 69.8% sensitive and 58.1% specific at a cut‐off level of 17.2 ng/ml in predicting the need for intensive care unit (ICU) treatment. Conclusion AnxA1 levels may be a beneficial biomarker in the diagnosis of COVID‐19 pneumonia and in predicting the need for ICU treatment in patients with COVID‐19 pneumonia at the time of admission to the emergency department.