ABSTRACT
We report microwave synthesis of seven unique pyrimidine anchored derivatives (1-7) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1-7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1-7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC50 values of 89.24±1.36 µM and 89.37±1.17 µM, respectively. Molecular docking was performed for derivatives (1-7) on main protease for SARS-CoV-2 (PDB ID: 6LU7). Results revealed that most of the derivatives had superior or equivalent affinity for the 3CLpro, as determined by docking and binding energy scores. 6 topped the rest with highest binding energy score of -8.12 kcal/mol with inhibition constant reported as 1.11 µM. ADME, drug-likeness, and pharmacokinetics properties of 1-7 were tested using Swiss ADME tool. Toxicity analysis was done with pkCSM online server. All derivatives showed high GI absorption. Except 1 and 3, all derivatives showed blood brain barrier permeability. Most derivatives showed negative logKp values suggesting derivatives are less skin permeable and bioavailability score of all derivatives was 0.55. The toxicity analysis demonstrated that all derivatives have no skin sensitization properties. 6 and 7 showed maximum tolerated dose (Human) values of -0.03 and -0.018, respectively and absence of AMES toxicity.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has numerous effects on different systemic organs other than the lungs. In this case report, we look at the presentation of a young female who was diagnosed with autoimmune hemolytic anemia (AIHA), kidney injury and thrombocytopenia during coronavirus disease 2019 (COVID-19) infection. She recovered well without the need for steroids. As demonstrated by this case, COVID-19 infection can be associated with the development of AIHA. The purpose of this report is to indicate that COVID-19 can present unusually with different clinical manifestations enough to require hospitalization.
ABSTRACT
After one year, the COVID-19 pandemic caused by SARS-CoV-2 is still the largest concern for the scientific community. Of the many recognized drug targets of SARS-CoV-2, the main protease is one of the most important target due to its function in viral replication. We conducted an in silico study with repurposing drugs of antibiotics class against virus protease and peptidase using AutoDock tool. The following significant binding energy interaction was observed with protease (PDB: 6LU7) like piperacillin -7.25; tobramycin -9.20 and doxorubicin (Doxo) -10.04 kcal/mol and with peptidase (PDB: 2GTB) piperacillin -7.08; tobramycin -8.54 and Doxo -9.89 kcal/mol. Furthermore, the interaction and stability behavior of the Doxo-protease and Doxo-peptidase complexes were analyzed for a 100-nanosecond (ns) time. Calculated RMSD values observed using molecular dynamics simulation (MDS) were found to be 0.15-0.25 nm, RMSF calculation per residues showed a value near 0.2 nm and Rg values remained approximately 2.25 nm. MM-PBSA analysis of total binding energy calculation of Doxo-protease and Doxo-peptidase complexes are found to be -148.692 and -105.367 kJ/mol, respectively. Moreover, amino acid residue ASP-197 showed the lowest contribution binding energy i.e. -18.1185 kJ/mol, and amino acid residue ASP-187 showed -17.0267 kJ/mol contribution energy. Thus, significant docking interaction and stable dynamicity of Doxo-protease complex with time was suggested that Doxo could be a choice to inhibit potentially the viral proteases that could prevent the entry inside the host cell to control the COVID-19 disease. Communicated by Ramaswamy H. Sarma.
Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Amino Acids , Anti-Bacterial Agents , Doxorubicin/pharmacology , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Pandemics , Peptide Hydrolases/metabolism , Piperacillin , Protease Inhibitors/chemistry , Tobramycin , Viral Nonstructural Proteins/chemistry , Viral ProteasesABSTRACT
COVID-19 is a viral disease with a high infectivity rate. The full spectrum of the disease is not yet understood. This understanding may help in limiting potential exposure. We present a young man with diarrhoea, abdominal pain and hyponatraemia who turned out to be positive for COVID-19.
Subject(s)
Abdominal Pain/diagnosis , Betacoronavirus/isolation & purification , Chloroquine/analogs & derivatives , Darunavir/administration & dosage , Diarrhea , Hyponatremia , Pneumonia, Viral , Ribavirin/administration & dosage , Abdominal Pain/etiology , Adult , Antimalarials/administration & dosage , Antiviral Agents/administration & dosage , COVID-19 , Chloroquine/administration & dosage , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Diagnosis, Differential , Diarrhea/diagnosis , Diarrhea/etiology , Humans , Hyponatremia/diagnosis , Hyponatremia/etiology , Male , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/etiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , SARS-CoV-2 , Treatment OutcomeABSTRACT
The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is one of the most common causes of hyponatremia in hospitalized patients. Wide spectrum of etiologies associated with hyponatremia pose significant challenges in detecting and treating this disorder. Several infectious causes of SIADH have been reported; however, hyponatremia associated with SIADH and Coronavirus disease 2019 (COVID-19) was only recently mentioned in a few case reports. We discuss a unique presentation of COVID-19, in which the patient presented with acute severe symptomatic hyponatremia thought to be the initial and isolated presentation of SARS-CoV-2 infection.