Coronavirus Disease 2019 Vaccine Development: An Overview.

To this day, the coronavirus disease 2019 (COVID-19) pandemic has not shown signs of abating. Moreover, the virus responsible for the pandemic, severe acute respiratory syndrome coronavirus 2, has evolved into three different variants. This phenomenon highlights an even greater need to develop drugs and vaccines to control the rate of infection and spread of the disease. As of July 7, 2020, at least 160 vaccine candidates, 21 of which have entered the clinical trial phase, have been developed. This article describes the latest advances in development, reliable platforms, strategies used, and challenges that remain in developing COVID-19 vaccines.

Molecular Docking Simulation Studies of Curcumin and Its Derivatives as Cyclin-Dependent Kinase 2 Inhibitors.

OBJECTIVES: Cyclin-dependent kinase 2 (CDK2) is a protein that plays a role in regulating the cell cycle and its overexpression contributes to uncontrolled cell proliferation. Inhibition of CDK2 is known to be a mechanism of action of various anti-cancer drugs. Curcumin is an active compound of Curcuma longa and it has been reported to inhibit the activity of cyclin D, cyclin E, CDK2, CDK4, and CDK6. This study aimed to design more active curcumin derivatives as anticancer drugs by targeting CDK2 through a molecular modeling approach. MATERIALS AND METHODS: The molecular modeling approach consists of receptor and ligand preparation, method validation, pharmacophore modeling, and docking simulation. RESULTS: The results of the molecular docking simulation show that the free bonding energy (ΔG) of curcumin and kurkumod 23 and 24 (the best modification of curcumin) are -7.80, -9.15, and -9.36 kcal/mol, respectively. The hydrogen interaction between kurkumod 23 and 24 with CDK occurred on Lys33 residue, which is considered a potential interaction site for CDK2 inhibitor compounds. Pharmacophore modeling showed that kurkumod 23 and 24 have pharmacophore-fit values of 45.20% and 47.26%, respectively. CONCLUSION: The results of this study indicate that kurkumod 23 and 24 are the best and most potent modifications of curcumin as CDK2 antagonist, based on the interactions that occur between these two derivatives with amino acid residues from the CDK2 receptor.

Effect of genetic polymorphisms on Alzheimer's disease treatment outcomes: an update.

Genetic variations in individuals may cause differences in the response to cholinesterase inhibitor drugs used in the treatment of Alzheimer's disease (AD). Through this review, we aimed to understand the potential relationship between genetic polymorphisms and treatment response in AD. We conducted a systematic review of the studies published from 2006 to 2018 that assessed the relationship between genetic polymorphisms and the pharmacotherapeutic outcomes of patients with AD. Via several possible mechanisms, genetic polymorphisms of many genes, including ABCA1, ApoE3, CYP2D6, CHAT, CHRNA7, and ESR1, appear to have strong correlations with the treatment response of patients with AD. Indeed, these genetic polymorphisms, either in the form of single nucleotide polymorphisms or direct changes to one or more amino acids, have been shown to cause differences in the therapeutic response. In summary, our findings indicate that genetic polymorphisms should be considered in the management of AD to achieve both effective and efficient treatment outcomes in terms of cost and prognosis.

Polymorphism of TPH2 Gene rs120074175 Is Not Associated with Risk Factors of Schizophrenia.

CONTEXT: Polymorphism on tryptophan hydroxylase 2 (TPH2) gene rs120074175 can cause the synthesis of neurotransmitter serotonin in the brain to reduce up to 80%. Reduced serotonin in the brain can cause dopamine release to occur continuously. Excess dopamine in the brain may cause positive symptom of schizophrenia. AIM: The aim of this study was to investigate the genotype distribution of TPH2 rs120074175 gene on patients with schizophrenia at Prof. Dr. Soerojo Magelang Psychiatric Hospital, Indonesia, and the relationship between the genetic polymorphism of the TPH2 rs120074175 gene against risk factors of schizophrenia. SETTINGS AND DESIGN: This was a cross-sectional study. MATERIALS AND METHODS: The method used was amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Whole blood from healthy subjects and patients with schizophrenia, Wizard genomic deoxyribonucleic acid (DNA) purification kit (Promega, Fitchburg, Wisconsin), PCR master mix (Promega), ARMS-PCR primers, ddH2O, agarose (Thermo Scientific, Seoul, South Korea), Tris, Acetic Acid, EDTA (TAE) 1X, ethidium bromide, loading dye 6×, and DNA ladder (Thermo Scientific) were the materials used. STATISTICAL ANALYSIS: Hardy-Weinberg equilibrium and chi-square (χ2) tests were used. RESULTS: The results showed that both groups (healthy subjects and patients with schizophrenia) at the Prof. Dr. Soerojo Magelang Psychiatric Hospital have a wild-type GG genotype (100%) without anyone having a mutant A allele. CONCLUSION: TPH2 rs120074175 gene polymorphism was not associated with risk factors for schizophrenia.

Single-nucleotide Polymorphism of CTLA-4 (rs5742909) in Correlation with Schizophrenia Risk Factor.

BACKGROUND: Cytotoxic T protein lymphocyte antigen-4 (CTLA-4) plays a key role in regulating the T-cell system, where occurrence of disturbances in the system seen by imbalances in Th1 and Th2 levels is believed to be one of the etiologies of schizophrenia. Single-nucleotide polymorphisms (SNPs) at rs5742909 in the CTLA-4 gene (C→T) might affect the expression level of CTLA-4 protein. AIMS AND OBJECTIVES: The aim of this study was to determine the genotype distribution of the CTLA-4 gene (rs5742909) in patients with schizophrenia at Rumah Sakit Jiwa Prof. Dr. Soerojo Magelang and identify the correlation of these genetic polymorphisms as the risk factors of schizophrenia. MATERIALS AND METHODS: This research was conducted through the stage of submitting ethical approval, primer design, chromosomal DNA isolation, optimization of polymerase chain reaction conditions, and data analysis. RESULTS: Based on the results of the study, the CC genotype was shown in 36 patients (78.26%), TT genotype in 10 patients (21.73%), and no TT genotypes. However, statistical analysis using Fisher's exact and binary logistic regression statistical test showed no significant relationship between genetic polymorphism of the CTLA-4 rs5742909 against risk factors for schizophrenia (P = 0.05; α = 5%). CONCLUSION: SNP at rs5742909, C-to-T-allele transition, was not significant associated with the risk of schizophrenia.