SARS-CoV-2 spike evolutionary behaviors; simulation of N501Y mutation outcomes in terms of immunogenicity and structural characteristic.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a large number of mutations in its genome have been reported. Some of the mutations occur in noncoding regions without affecting the pathobiology of the virus, while mutations in coding regions are significant. One of the regions where a mutation can occur, affecting the function of the virus is at the receptor-binding domain (RBD) of the spike protein. RBD interacts with angiotensin-converting enzyme 2 (ACE2) and facilitates the entry of the virus into the host cells. There is a lot of focus on RBD mutations, especially the displacement of N501Y which is observed in the UK/Kent, South Africa, and Brazilian lineages of SARS-CoV-2. Our group utilizes computational biology approaches such as immunoinformatics, protein-protein interaction analysis, molecular dynamics, free energy computation, and tertiary structure analysis to disclose the consequences of N501Y mutation at the molecular level. Surprisingly, we discovered that this mutation reduces the immunogenicity of the spike protein; also, displacement of Asn with Tyr reduces protein compactness and significantly increases the stability of the spike protein and its affinity to ACE2. Moreover, following the N501Y mutation secondary structure and folding of the spike protein changed dramatically.

A multicenter retrospective study of clinical features, laboratory characteristics, and outcomes of 166 hospitalized children with coronavirus disease 2019 (COVID-19): A preliminary report from Iranian Network for Research in Viral Diseases (INRVD).

BACKGROUND: The objectives of this study were to analyze the clinical features and laboratory profiles and risk factors associated with critical illness of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: One hundred and sixty-six coronavirus disease 2019 (COVID-19) Iranian pediatric patients were recruited through a collaborative research network between March and May 2020. Demographics, clinical, laboratory, and radiological results were obtained from patient files. RESULTS: Of 166 patients, 102 (61%) and 64 (39%) were males and females, respectively. Ninety-six (57.8%) and 70 (42.2%), had moderate and severe conditions, respectively. Thirty (18%) of patients died. The common symptoms were fever (73%), cough (54%), and shortness of breath, headache decrease in neutrophil and platelet counts; increase values in lactate dehydrogenase, decrease in the blood pH and HCO3 were significantly associated with the disease severity. 54% and 56% of patients showed abnormal radiographic appearance in Chest X-ray and in chest computed tomography scan, respectively. Sixty-one (36.7%) of patients were referred to intensive care unit (ICU). The coexistence of comorbidity was the main factor associated with ICU admission, shock, arrhythmia, acute kidney injury, acute respiratory distress syndrome, acute cardiac injury, and death. CONCLUSIONS: We describe a higher than previously recognized rate of COVID-19 mortality in Iranian pediatric patients. Epidemiological factors, such as the relatively high case fatality rate in the country and the presence of underlying diseases were the main factors for the high death rate.

Efficacy of botulinum toxin type a for treating chronic low back pain.

BACKGROUND: Low back pain is a major cause of disability and can result in substantial morbidity and high healthcare costs. Botulinum toxin has been used successfully to alleviate pain for a number of conditions caused by muscle contractions or spasms. OBJECTIVES: The aim of this study was to investigate the efficacy of botulinum toxin type A (BoNT-A; Dysport®, Ipsen, UK) for treating chronic low back pain (CLBP). PATIENTS AND METHODS: This was a single-blind, randomized clinical trial study. Fifty patients with CLBP received either BoNT-A (40 Ipsen units per injection) or saline in 5 sites in the paraspinal muscles (n = 25 per group). A visual analogue system (VAS) was used to measure pain levels at baseline and at 4 and 8 weeks post-injection. Disability was assessed using the Oswestry low back pain disability questionnaire at baseline and at 8 weeks post-injection. RESULTS: After 4 weeks, 76% of patients in the BoNT-A group reported pain relief compared to 20% in the saline group (P < 0. 005). Additionally, greater pain relief was experienced by patients in the BoNT-A group at 8 weeks (64% vs. 12%; P < 0. 001). By week 8, significant functional improvement (a minimum two-grade improvement between baseline and post-treatment assessments) was demonstrated in a higher number of patients receiving BoNT-A than in the saline group (68% vs. 12% , respectively; P < 0. 005). Patients experienced only minor side effects. CONCLUSIONS: BoNT-A improves CLBP with a low incidence of side effects and can be used as a therapeutic tool in the management of these patients.