ABSTRACT
OBJECTIVES: To describe the clinical characteristics of paediatric patients admitted to a single paediatric intensive care unit (PICU) in Iran with COVID-19. METHODS: A cross-sectional study of paediatric patients who were admitted to a COVID-19-dedicated PICU from 16 March 2020 to 21 April 2020 with COVID-19. RESULTS: Six children had confirmed COVID-19 and four had suspected COVID-19. Six had pre-existing chronic medical conditions. Nine had respiratory failure and needed ventilation. Five children, of whom four had chronic medical conditions, died. Four had cardiac arrhythmias. Clinical presentation included fever and cough. CONCLUSION: COVID-19 can be fatal in paediatric patients, especially in those with a chronic medical condition.
ABSTRACT
Considering the urgency of the COVID-19 pandemic, we developed a receptor-based pharmacophore model for identifying FDA-approved drugs and hits from natural products. The COVID-19 main protease (Mpro) was selected for the development of the pharmacophore model. The model consisted of a hydrogen bond acceptor, donor, and hydrophobic features. These features demonstrated good corroboration with a previously reported model that was used to validate the present model, showing an RMSD value of 0.32. The virtual screening was carried out using the ZINC database. A set of 208,000 hits was extracted and filtered using the ligand pharmacophore mapping, applying the lead-like properties. Lipinski's filter and the fit value filter were used to minimize hits to the top 2000. Simultaneous docking was carried out for 200 hits for natural drugs belonging to the FDA-approved drug database. The top 28 hits from these experiments, with promising predicted pharmacodynamic and pharmacokinetic properties, are reported here. To optimize these hits as Mpro inhibitors and potential treatment options for COVID-19, bench work investigations are needed.
Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Biological Products/chemistry , Biological Products/pharmacology , COVID-19 Drug Treatment , Receptors, Drug/metabolism , Binding Sites , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/metabolism , Databases, Pharmaceutical , Drug Discovery , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Ligands , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Binding , Quantitative Structure-Activity RelationshipABSTRACT
The hunt for potential lead/drug molecules from different resources, especially from natural resources, for possible treatment of COVID-19 is ongoing. Several compounds have already been identified, but only a few are good enough to show potential against the virus. Among the identified druggable target proteins of SARS-CoV-2, this study focuses on non-structural RNA-dependent RNA polymerase protein (RdRp), a well-known enzyme for both viral genome replication and viral mRNA synthesis, and is therefore considered to be the primary target. In this study, the virtual screening followed by an in-depth docking study of the Compounds Library found that natural compound Cyclocurcumin and Silybin B have strong interaction with RdRp and much better than the remdesivir with free binding energy and inhibition constant value as êzÅ-6.29 kcal/mol and 58.39 µMêzÅ, and êzÅ-7.93kcal/mol and 45.3 µMêzÅ, respectively. The finding indicated that the selected hits (Cyclocurcumin and Silybin B) could act as non-nucleotide anti-polymerase agents, and can be further optimized as a potential inhibitor of RdRp by benchwork experiments.
Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/metabolism , Biological Products/metabolism , COVID-19/metabolism , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Drug Discovery/methods , Molecular Docking Simulation/methods , Phytochemicals/metabolism , SARS-CoV-2/enzymology , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/metabolism , Alanine/chemistry , Alanine/metabolism , Antiviral Agents/chemistry , Biological Products/chemistry , COVID-19/virology , Catalytic Domain , Coronavirus RNA-Dependent RNA Polymerase/antagonists & inhibitors , Coronavirus RNA-Dependent RNA Polymerase/chemistry , Curcumin/analogs & derivatives , Curcumin/chemistry , Curcumin/metabolism , Databases, Protein , Drug Evaluation, Preclinical/methods , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Phytochemicals/chemistry , Protein Binding , Silybin/chemistry , Silybin/metabolismABSTRACT
The confirmed cases with COVID-19 in children account for just 1% of the overall confirmed cases. Severe COVID-19 in children is rare. Case Presentation: Our patient was 16 years old with a severe case of COVID-19 and did not survive due to the presence of Granulomatosis with polyangiitis and being treated with immunosuppressive drugs. We used lopinavir, ritonavir, hydroxy chloroquine, intravenous immunoglobulin and continuous veno-venous hemodialysis for treatment. Conclusion: In this patient, an underlying disease and delayed admission to the hospital were two factors complicating his condition.
ABSTRACT
SARS-CoV-2 is a positive-stranded RNA virus that bundles its genomic material as messenger-sense RNA in infectious virions and replicates these genomes through RNA intermediates. Several virus-encoded nonstructural proteins play a key role during the viral life cycle. Endoribonuclease NSP15 is vital for the replication and life cycle of the virus, and is thus considered a compelling druggable target. Here, we performed a combination of multiscoring virtual screening and molecular docking of a library of 1624 natural compounds (Nuclei of Bioassays, Ecophysiology and Biosynthesis of Natural Products (NuBBE) database) on the active sites of NSP15 (PDB:6VWW). After sequential high-throughput screening by LibDock and GOLD, docking optimization by CDOCKER, and final scoring by calculating binding energies, top-ranked compounds NuBBE-1970 and NuBBE-242 were further investigated via an indepth molecular-docking and molecular-dynamics simulation of 60 ns, which revealed that the binding of these two compounds with active site residues of NSP15 was sufficiently strong and stable. The findings strongly suggest that further optimization and clinical investigations of these potent compounds may lead to effective SARS-CoV-2 treatment.
Subject(s)
Antiviral Agents/pharmacology , Endoribonucleases/chemistry , High-Throughput Screening Assays/methods , Viral Nonstructural Proteins/chemistry , Antiviral Agents/chemistry , Antiviral Agents/pharmacokinetics , Catalytic Domain , Endoribonucleases/metabolism , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Ligands , Molecular Docking Simulation , Molecular Dynamics Simulation , Viral Nonstructural Proteins/metabolism , COVID-19 Drug TreatmentABSTRACT
It was December 2019 that china reported series of patients with respiratory symptoms, a disease that later named COVID-19; and from there spread to other countries around the world; and in February 2020, the world health organization declared COVID-19 as a pandemic. From the beginning, it was assumed that COVID-19 occurrence in pediatric patients is less and has less severity but nowadays; there are a reports that shows severe cases with multiple organ involvement. The most manifestation symptom is fever but convulsion is rare as the first manifestation symptom. Here we describe a 3 years old; previously healthy boy that presented with repeated fever induced seizure and status epilepticus and positive RT-PCR for COVID-19 that in the first day; brain CT scan revealed brain edema and 5 days later, there was intracerebral hemorrhage in brain MRI.
ABSTRACT
Coronavirus disease 2019 (COVID-19) first emerged in Wuhan, China, in December 2019. Then, it spread to the whole world so that THE World Health Organization (WHO) declared a worldwide pandemic on March 11, 2020. Coronavirus disease 2019 is a novel and mysterious infectious disease that causes respiratory illness, multiorgan failure (MOF), and death. Although pediatric COVID-19 accounts for a small percentage of patients and is often milder than in adults, it can progress to severe disease in some cases. Liver involvement in COVID-19 and its severity have not been clearly investigated. In this paper, we present an 11-year-old boy admitted to a Pediatric Intensive Care Unit (PICU) with COVID-19 diagnosis in combination with elevated liver enzymes and bilirubin.