An in silico investigation of allosteric inhibition potential of Dihydroergotamine against Sars-CoV-2 Main Protease (MPro)

Possible allosteric inhibitors of MPro were investigated using in silico methods. To this end, FDA-approved drugs in the DrugBank database were subjected to a virtual screening, and drugs that strongly bind distant from the catalytic site of MPro were identified using molecular docking. Among the identified drugs, Dihydroergotamine (DHE) was chosen for further investigation due to its highest binding score against MPro in the molecular docking experiment. The allosteric inhibition potential of DHE toward MPro was demonstrated by applying some computational tools on the trajectory files which were obtained from the Molecular Dynamics Simulations. Results support that the hydrogen bonding interactions of DHE with GLU278 and THR280, located between Protomer A and Protomer B, affect the structure of the side chain of CYS145 at the catalytic site of MPro. Considering the role of CYS145 in the catalytic cycle, this structural change is likely to be a mechanism for inhibiting MPro. © 2023,Turkish Computational and Theoretical Chemistry.All Rights Reserved.

Evaluation of the frequency and intensity of COVID-19 in patients with ankylosing spondylitis under anti-TNF therapy

BACKGROUND: This study aimed to investigate pregnancy frequency and evaluate the factors affecting live births in hemodialysis (HD) patients. METHODS: Female HD patients whose pregnancy was retrospectively reported between January 1, 2014, and December 31, 2019. The duration of HD, primary disease, and the information on whether the pregnancy resulted in abortion, stillbirth, or live birth, whether the HD duration was prolonged after diagnosing the pregnancy and whether it accompanied preeclampsia were recorded. RESULTS: In this study, we reached 9038 HD female patients' data in the study. A total of 235 pregnancies were detected in 145 patients. The mean age was 35.42 (35 ± 7.4) years. The mean age at first gestation was 30.8 ± 6.5 years. The average birth week was 32 (28 -36) weeks. A total of 53.8% (no = 78) of the patients had live birth, 51.7% (no = 70) had at least one abortion in the first 20 weeks, and 13.1% (no = 19) had at least one stillbirth after 20 weeks. The rate of patients' increased numbers of dialysis sessions during pregnancy was 71.7%. The abortion rate was 22.4% in those with increased HD sessions, whereas 79.3% in those not increased HD sessions (p < 0.001). Live birth frequency was 67.2% in the increased HD sessions group and 3.4% in those who did not differ in HD sessions (p < 0.001). DISCUSSION: For the first time, we reported pregnancy outcomes in HD female patients, covering all regions of Turkey. It has been observed that;increasing the number of HD sessions in dialysis patients will decrease fetal and maternal complications and increase live birth rates.

Sir Mathematical model and estimating of COVID-19 epidemic spreading

The SIR (susceptible-infected-recovered) Epidemic Model has been utilized effectively in the struggle against past pandemics and has been useful. One can find a discussion here on six Mediterranean countries to support states' fight against the COVID-19 pandemic. The model, which consists of three separate autonomous differential equations, can grant estimations of infected individuals, the future of the pandemic, and predictions for vaccination. The paper estimates the number of infected individuals with a relatively low error rate. While determining the condition of the pandemic with the aid of the (Basic) Reproduction Number (Ro), it creates scenarios about vaccination with the Herd Immune Threshold (Ht) coefficient. The conclusions belong to the struggle of the Mediterranean Basin countries Albania, Israel, Algeria, France, Tunisia, and Morocco.

Impact of proactive low-molecular weight heparin therapy on outcomes in COVID-1.

OBJECTIVES: Low molecular weight heparin (LMWH) may provide beneficial effects on outcomes of COVID-19. We aimed to examine the impact of LMWH treatment on clinical outcomes (duration of hospitalization, admission to intensive care unit, the requirement for mechanical ventilation, and death) of COVID-19 patients with normal D-dimer levels at admission. BACKGROUND: Coronavirus disease-2019 (COVID-19) predisposes patients to arterial and venous thrombosis. METHODS: In this retrospective, multicentre and observational study we analysed the data of 308 confirmed COVID-19 patients with normal D-dimer levels at initial admission. After propensity score matching (PSM) patients were grouped; Group 1; patients who received LMWH with D-dimer ≤0.5 mg/L, Group 2; patients who received LMWH after D-dimer levels exceeded 0.5 mg/L, and Group 3; patients who did not receive LMWH. RESULTS: After PSM, each group comprised 40 patients. The patients in Group1 had the best clinical outcomes compared to the other groups. Group 3 had the worst clinical outcomes (p<0.005). The benefit of LMWH increased with early prophylactic therapy especially when started while the D-dimer levels were ≤0.5 mg/L. CONCLUSION: Our results strongly suggest that proactive LMWH therapy improves clinical outcomes in hospitalized COVID-19 patients even with normal D-dimer levels (≤ 0.5 mg/L) (Tab. 3, Fig. 2, Ref. 34).

Overview of favipiravir and remdesivir treatment for COVID-19

The current coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the wholesale market in Wuhan, China in the last months of 2019 and spread to almost all countries of the world. Although several vaccines have already been developed in different countries of the world, there is currently no specific treatment for COVID-19. Some agents are used all over the world based on in-vitro, in-vivo studies, and randomized controlled studies. The number of studies on antiviral therapy has been increasing day by day. However, the efficacy of antiviral drugs for COVID-19 remains controversial. In this review, brief information about antiviral drugs favipiravir and remdesivir used for the treatment of COVID-19, the results of the conducted studies, and the possible adverse effects of these drugs are summarized. We hope that this review will provide an impression of favipiravir and remdesivir used to treat and control COVID-19 patients until the approval of specific drugs that target SARS-CoV-2.