Non-Structural Protein 16 (nsp-16), a viral RNA methyltransferase (MTase), is one of the highly viable targets for drug discovery of coronaviruses including SARS-CoV-2. In this study, drug discovery of SARS-CoV-2 nsp-16 has been performed by a virtual drug repurposing approach. First, drug shapebased screening (among FDA approved drugs) with a known template of MTase inhibitor, sinefungin was done and best compounds with high similarity scores were selected. In addition to the selected compounds, 4 nucleoside analogs of anti-viral (Raltgravir, Maraviroc and Favipiravir) and anti-inflammatory (Prednisolone) drugs were selected for further investigations. Then, binding energies and interaction modes were found by molecular docking approaches and compouds with lower energy were selected for further investigation. After that, Molecular dynamics (MD) simulation was carried to test the potential selected compounds in a realistic environment. The results showed that Raltegravir and Maraviroc among other compounds can bind strongly to the active site of the protein compared to sinefungin, and can be potential candidates to inhibit NSP-16. Also, the MD simulation results suggested that the Maraviroc and Raltegravir are more effective drug candidates than Sinefungin for inhibiting the enzyme. It is concluded that Raltegravir and Maraviroc which may be used in the treatment of COVID-19 after Invitro and invivo studies and clinical trial for final confirmation of drug effectiveness.
Background/Aim:Thrombocytopenia is a common finding in patients with cirrhosis and may lead to unnecessary referral for bone marrow (BM) biopsy. To date, the prevalence of cirrhosis in patients with thrombocytopenia who receive BM biopsy is largely unknown.Materials and Methods:Between fiscal years 2006-2010, 744 patients (≥18 years) who underwent BM biopsies for thrombocytopenia at our hospital were identified retrospectively. 541 patients were excluded who had hematologic malignancies and received chemotherapy. Remaining 203 patients with predominant isolated thrombocytopenia were included in the study.Results:Of 203 patients, 136 (67%) had a normal and 67 (33%) had an abnormal BM examination. Prevalence of cirrhosis in the study population was 35% (95% CI: 28.4-41.9). 51% patients with normal BM were found to have cirrhosis compared to 3% of patients with abnormal BM exam (P < 0.0001). Common causes of cirrhosis were nonalcoholic steatohepatitis (NASH) (47%), followed by alcohol and Hepatitis C virus infection. Idiopathic thrombocytopenia and myelodysplastic syndrome were most frequent causes of thrombocytopenia in patients without cirrhosis. Patients with NASH had higher body mass index (BMI) (33.4 vs. 25.8, P < 0.001) and lower MELD scores (11.1 vs. 16, P = 0.028) when compared to non-NASH patients with cirrhosis.Conclusion:Approximately, one third (35%) of patients with cirrhosis induced thrombocytopenia may undergo unwarranted BM biopsies. Clinical diagnosis of cirrhosis is still a challenge for many physicians, particularly with underlying NASH. We propose cirrhosis to be the prime cause of isolated thrombocytopenia.
Chronic hepatitis B virus (HBV) infection may result in cirrhosis and/or hepatocellular carcinoma and is one of the leading causes of mortality in Asian Americans including Hmong Americans. The Central California Valley is home to a huge Hmong population. To date, the true prevalence of HBV among Hmong is largely unknown. The aim of this study was to contribute to the limited data on HBV prevalence and its trends in Hmong population in the Central California Valley. Between fiscal years 2006 and 2010, a total of 219, 450 voluntary donors were identified at Central California Blood Center in Fresno. Of these, 821 (399 males and 422 females) were Hmong donors. A cross-sectional review of the HBV (hepatitis B surface antigen) positivity among all donors was carried out. Prevalence estimates with 95% confidence intervals (CI) were calculated. Ninety-two percent of Hmong donors were between age groups 16 and 35 years, and only 8% were ≥36 years. The overall prevalence in Hmong was noted at 3.41% (95%CI 2.3-4.9) compared to 0.06% (95%CI 0.05-0.07) in donors of all ethnicities. The calculated prevalence could be an underestimate of the true HBV prevalence in Hmong as the study enrolled only healthy blood donors with predominant younger age (≤35 years) population. These results underscore the persistent burden of HBV infection and potentially increased risk of premature death even in the second generation Hmong community of the Central California Valley. This study reemphasizes the unequivocal need to develop robust preventive and treatment strategies for HBV in Hmong community.
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