Variable Proportions of Phylogenetic Clustering and Low Levels of Antiviral Drug Resistance among the Major HBV Sub-Genotypes in the Middle East and North Africa

Hepatitis B virus (HBV) infection remains a major public health threat in the Middle East and North Africa (MENA). Phylogenetic analysis of HBV can be helpful to study the putative transmission links and patterns of inter-country spread of the virus. The objectives of the current study were to analyze the HBV genotype/sub-genotype (SGT) distribution, reverse transcriptase (RT), and surface (S) gene mutations and to investigate the domestic transmission of HBV in the MENA. All HBV molecular sequences collected in the MENA were retrieved from GenBank as of 30 April 2021. Determination of genotypes/SGT, RT, and S mutations were based on the Geno2pheno (hbv) 2.0 online tool. For the most prevalent HBV SGTs, maximum likelihood phylogenetic analysis was conducted to identify the putative phylogenetic clusters, with approximate Shimodaira–Hasegawa-like likelihood ratio test values ≥ 0.90, and genetic distance cut-off values ≤ 0.025 substitutions/site as implemented in Cluster Picker. The total number of HBV sequences used for genotype/SGT determination was 4352 that represented a total of 20 MENA countries, with a majority from Iran (n = 2103, 48.3%), Saudi Arabia (n = 503, 11.6%), Tunisia (n = 395, 9.1%), and Turkey (n = 267, 6.1%). Genotype D dominated infections in the MENA (86.6%), followed by genotype A (4.1%), with SGT D1 as the most common in 14 MENA countries and SGT D7 dominance in the Maghreb. The highest prevalence of antiviral drug resistance was observed against lamivudine (4.5%) and telbivudine (4.3%). The proportion of domestic phylogenetic clustering was the highest for SGT D7 (61.9%), followed by SGT D2 (28.2%) and genotype E (25.7%). The largest fraction of domestic clusters with evidence of inter-country spread within the MENA was seen in SGT D7 (81.3%). Small networks (containing 3-14 sequences) dominated among domestic phylogenetic clusters. Specific patterns of HBV genetic diversity were seen in the MENA with SGT D1 dominance in the Levant, Iran, and Turkey; SGT D7 dominance in the Maghreb; and extensive diversity in Saudi Arabia and Egypt. A low prevalence of lamivudine, telbivudine, and entecavir drug resistance was observed in the region, with almost an absence of resistance to tenofovir and adefovir. Variable proportions of phylogenetic clustering indicated prominent domestic transmission of SGT D7 (particularly in the Maghreb) and relatively high levels of virus mobility in SGT D1.

The effects of selenium in the prevention and treatment of Coronavirus disease 2019: A Review

The coronavirus disease 2019 (COVID-19), is an ongoing global pandemic and caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is transmitted between people through respiratory droplets. Because of antiviral drug resistance and virus mutation, the treatment of covid-19 disease is facing a new challenge. Therefore, have been proposed that micronutrients can be used for strengthen the immune system as new antiviral strategies. Selenium plays an important role in immune function through its incorporation in antioxidant and anti-inflammatory activity. There is a very strong evidence that is link between selenium status and susceptibility of humans to a viral infection. Recently published studies demonstrates that serum level of selenium was lower in patients with SARS-CoV-2 infection compared to in healthy individuals. Also, the results of these study demonstrated that the serum selenium level deficiency increased the mortality rate of COVID-19. Thus, selenium supplementation can possibly be used for the prevention or treatment of patients infected with SARS-CoV-2 in selenium-deficient status. Key words: COVID-19, SARS-CoV-2, Selenium, Selenium-deficient, Mortality rate

Small-Molecule Inhibitors of Chikungunya Virus: Mechanisms of Action and Antiviral Drug Resistance

ABSTRACT Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has spread to more than 60 countries worldwide. CHIKV infection leads to a febrile illness known as chikungunya fever (CHIKF), which is characterized by long-lasting and debilitating joint and muscle pain. CHIKV can cause large-scale epidemics with high attack rates, which substantiates the need for development of effective therapeutics suitable for outbreak containment. In this review, we highlight the different strategies used for developing CHIKV small-molecule inhibitors, ranging from high-throughput cell-based screening to in silico screens and enzymatic assays with purified viral proteins. We further discuss the current status of the most promising molecules, including in vitro and in vivo findings. In particular, we focus on describing host and/or viral targets, mode of action, and mechanisms of antiviral drug resistance and associated mutations. Knowledge of the key molecular determinants of drug resistance will aid selection of the most promising antiviral agent(s) for clinical use. For these reasons, we also summarize the available information about drug-resistant phenotypes in Aedes mosquito vectors. From this review, it is evident that more of the active molecules need to be evaluated in preclinical and clinical models to address the current lack of antiviral treatment for CHIKF.

1746. Prevalence and Resistance Patterns of Cytomegalovirus Viremia in Immunocompromised Patients

Background We noted a recent increase in the number of patients with CMV viremia among immunocompromised children at our institution. The study was undertaken to determine the prevalence of CMV viremia and to evaluate factors associated with the development of antiviral drug resistance. Methods A retrospective study of immunocompromised hosts 0–21 years of age who had CMV viremia (2007–2017). We collected demographic data as well as details of antiviral therapy and resistance testing. Results A total of 31 patients were identified including 10 (32%) during the last 2 years. The age range was 3 months to 20 years (median 12.6 years); 23 (74%) were male and 12 (39%) were African American. Among the 31 patients, 18 had hematopoietic stem cell transplantation, 5 had primary immunodeficiency (2 common variable immunodeficiency, 1 SCID, 1 Langerhans cell histiocytosis, 1 DiGeorge syndrome), 4 had malignancies receiving chemotherapy, 3 with heart transplantation and one 17 year old with newly diagnosed HIV infection who presented with CMV pneumonia and viremia. Antiviral resistance testing was performed on 7 CMV isolates: 5 due to persistent viremia (> 1 months) despite treatment, and 2 prior to starting antiviral therapy. CMV resistance was identified in 3 patients including 2 with CVID and one with Hodgkin’s disease status post bone marrow transplantation. The 2 CVID patients had other comorbidities including chronic diarrhea and malabsorption and were TPN dependent. Both were diagnosed with CMV colitis and one also had pneumonitis. One had received a prolonged oral valganciclovir course (> 1 year) prior to diagnosis of resistance and the other received long-term intermittent oral valganciclovir courses. The patient with Hodgkin’s disease received a prolonged IV ganciclovir course. All 3 tested positive for UL97 mutation and one had both UL97/UL54 gene mutations. Conclusion Most of our patients with CMV viremia were transplant patients. Antiviral drug resistance was detected among 3 of 31 (10%) of our patients during the study period. Two had malabsorption that may have resulted in sub-therapeutic blood levels. Treatment with oral valganciclovir should be avoided in patients with poor gut absorption because it may increase risk of drug resistance. Disclosures All authors: No reported disclosures.

Mutations in the cytomegalovirus UL97 gene associated with ganciclovir resistance in recipients of allogeneic hematopoietic stem cell transplants

Objective. To identify mutations in UL97 gene associated with antiviral drug resistance in recipients of allogeneic hematopoietic stem cells transplants (allo-HSCT). Materials and Methods. A total of 9 HCMV DNA samples were studied. These samples were received from the blood of 8 allo-HSCT recipients who were infected with HCMV and undergoing treatment at NMRC of Hematology (Russia) over the period of 2016 to 2017. Sanger sequencing was used to find mutations. The sequenced part of the virus DNA was analyzed using nucleotide BLAST and Genome compiler. Mutations were identified using MRA program which compared the obtained nucleotide sequence with the reference sequence of UL97 gene from Merlin strain. Results. Rate of detection of viruses with mutations that may lead to drug resistance is relatively high – 3 of 8 patients. The following mutations were identified: C592G, C607F and C603W. The obtained data shows that the presence and characteristics of mutations affect the viral load and the time when HCMV DNA is identified in blood. Conclusions. Obtained data show that presence of mutations impacts the course infection, leading to higher viral load and longer persistence of viral DNA in blood samples. Identified mutations had different resistance factor, which also impacted on the pattern of infection.