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1.
PLoS One ; 17(12):e0276538, 2022.
Article in English | PubMed | ID: covidwho-2197027

ABSTRACT

Tumor necrosis factor-alpha (TNF-α) is a multifunctional pro-inflammatory cytokine, responsible for autoimmune and inflammatory disorders. In COVID-19 patients, increased TNF-α concentration may provoke inflammatory cascade and induce the initiation of cytokine storm that may result in fatal pneumonia and acute respiratory distress syndrome (ADRS). Hence, TNFα is assumed to be a promising drug target against cytokine storm in COVID-19 patients. In the present study, we focused on finding novel small molecules that can directly block TNF-α-hTNFR1 (human TNF receptor 1) interaction. In this regards, TNF-α-inhibiting capacity of natural carotenoids was investigated in terms of blocking TNF-α-hTNFR1 interaction in COVID-19 patients with the help of a combination of in silico approaches, based on virtual screening, molecular docking, and molecular dynamics (MD) simulation. A total of 125 carotenoids were selected out of 1204 natural molecules, based on their pharmacokinetics properties and they all met Lipinski's rule of five. Among them, Sorgomol, Strigol and Orobanchol had the most favorable ΔG with the best ADME (absorption, distribution, metabolism, excretion) properties, and were selected for MD simulation studies, which explored the complex stability and the impact of ligands on protein conformation. Our results showed that Sorgomol formed the most hydrogen bonds, resulting in the highest binding energy with lowest RMSD and RMSF, which made it the most appropriate candidate as TNF-α inhibitor. In conclusion, the present study could serve to expand possibilities to develop new therapeutic small molecules against TNF-α.

2.
Archives of Razi Institute ; 77(5):1611-1619, 2022.
Article in English | CAB Abstracts | ID: covidwho-2002783

ABSTRACT

Infectious bronchitis (IB) disease, avian Infectious Bronchitis disease in one of the major cause of respiratory problems and economic loss in poultry industry, even in developed countries with good biosecurity practice. Since the first isolation of the virus in 1931, a lot of serotypes and genotypes of the virus have been reported around the world. The GI-1 lineage, including Massachusetts (Mass) serotype viruses, is one of the most widely spread types worldwide. Moreover, the GI-23 lineage with a growing incidence rate was reported approximately 20 years ago in the Middle East, with no or little homologues vaccine use. The genotype was previously restricted to the Middle East;now, there is evidence that it has spread to European countries, raising concerns regarding potential outbreaks. In the present study, our attempt was to phylogenetically analyze the S1 gene of six isolates from Massachusetts and variant 2 genotypes, which were isolated from broiler and broiler breeder flocks in Iran. The variant 2 viruses were compared to other reported variant 2 viruses from neighboring countries and they had more than 98% identity with the latest reported Iranian variant 2. In addition, Three Mass type viruses were similar to vaccine strains which may be shows continuous circulation of vaccine viruses in the field. This event can cause increasing the risk of their mutation or even reversion to virulence after several passages in natural host, furthermore circulating viruses may recombinant with virulent field viruses and cause emergence of new variants. Considering the variable nature of IB viruses in which few changes lead to important differences, continuous epidemiological surveillance along with clinical studies of new isolates, are crucial to a better understanding of their pathogenicity and subsequent disease control.

3.
Journal of Babol University of Medical Sciences ; 24(1):205-214, 2022.
Article in Persian | EMBASE | ID: covidwho-1935330

ABSTRACT

Background and Objective: In the epidemic of COVID-19, intensive care units usually bear a heavy burden due to overcrowding of patients who need hospitalization, which can be due to liver involvement in these patients. This study was conducted to assess the relationship between liver enzymes in COVID-19 patients and the need for hospitalization in the intensive care unit, as well as to investigate its relationship with the length of stay in the intensive care unit. Methods: In this analytical cross-sectional study, 622 hospitalized patients with COVID-19 who referred to Firoozgar Hospital were investigated in terms of length of stay, recovery or death and its relationship with abnormal liver enzymes. Findings: The mean level of AST and ALT in people hospitalized in ICU was 49 (95% CI: 43.4-54.6) and 29.2 (95% CI: 24.1-34.2), respectively, and it was 42.5 (95% CI: 36.7-48.3) and 31.2 (95% CI: 25.8-36.6), respectively, in the general ward. The mean level of AST and ALT in patients hospitalized for less than 7 days was 49.4 (95% CI: 43.9-54.8) and 27 (95% CI: 21.6-32.3), respectively, and in patients hospitalized for more than 7 days was 41.6 (95% CI: 35.6-47.5) and 32.2 (95% CI: 37.3-27.1), respectively. None of the abnormal data was significant based on hospital department and length of stay. Conclusion: The results of this study did not show any significant relationship between the need for admission to ICU and the abnormal levels of liver enzymes. Furthermore, no relationship was found between the length of stay and the severity of liver involvement based on the assessment of abnormal liver enzymes.

4.
Military Medical Science Letters (Vojenske Zdravotnicke Listy) ; 90(4):172-190, 2021.
Article in English | Scopus | ID: covidwho-1566990

ABSTRACT

Coronavirus 2 (SARS-CoV-2) leads to Coronavirus disease 2019, is recognized as a lethal epidemic in 2020. SARS-CoV-2 is an enveloped, non-segmented, positive sense RNA virus that belongs to the beta-corona family of viruses. The genome of this virus is about 30 kb representing 16 non-structural proteins (Nsp1-16), four structural proteins (N, M, E, S) and nine accessory proteins are encoded by its genome, which are involved in survival and pathogenesis the viruses. In order to produce medicines and vaccines for SARS-CoV-2, it is essential to fully understand the genomic structure of the virus and function of its proteins. This review collects and investigates the functional properties of SARS-CoV-2 proteins that have been reported to date. © 2021, University of Defence, Faculty of Military Health Sciences. All rights reserved.

5.
Hepatitis Monthly ; 20(11), 2020.
Article in English | GIM | ID: covidwho-1073713

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [COVID-19] quickly turned into a pandemic. Gastrointestinal involvement, especially liver diseases, is one of the main complications of COVID-19 patients. Objectives: The current study aimed to evaluate the high incidence of liver involvement in COVID-19 hospitalized patients and its association with mortality.

6.
Hepatitis Monthly ; 20(11):1-6, 2020.
Article in English | EMBASE | ID: covidwho-1042682

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [COVID-19] quickly turned into a pandemic. Gastrointestinal involvement, especially liver diseases, is one of the main complications of COVID-19 patients. Objectives: The current study aimed to evaluate the high incidence of liver involvement in COVID-19 hospitalized patients and its association with mortality. Methods: A total of 560 hospitalized patients with a confirmed diagnosis of COVID-19 were included. Death was considered as the outcome. In addition to liver enzymes, demographic, clinical, and other laboratory data were also collected. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels_ 40 were considered as abnormal. To investigate the association between abnormal levels of liver enzymes and death, multiple regression logistic was used. Results: According to the findings, 29.1% (95% CI = 25.3% - 32.9%) of patients had high levels (_ 40 IU) of ALT, and 45.1% (95% CI = 40.9% - 49.3%) had high levels of AST (_ 40 IU). The frequency (based on %) of high levels of AST (_ 40 U/liter) was significantly higher in patients who died [67.3% (95% CI = 54.5% - 80.1%] of COVID-19 than those who survived [44.9% (95% CI = 39.7% - 50.0%)] (Pvalue < 0.001). No significant difference was detected in ALT between expired [29.1% (95% CI = 16.7% - 41.5%)] and survived patients [30.7% (95% CI = 25.9% - 35.5%] (P-value = 0.791). AST was found to have an independent association with death in multiple logistic regression (Wald = 4.429, OR (95% CI) = 1.014 (1.008 - 1.020), P-value = 0.035). Conclusions: Liver involvement is a common finding in COVID-19 hospitalized patients. Higher levels of AST were significantly associated with an increased mortality rate in COVID-19 patients.

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