Immunomodulatory and anti-cytokine therapeutic potential of curcumin and its derivatives for treating COVID-19 - a computational modeling.

The unavailability of vaccine and medicines raised serious issues during COVID-19 pandemic and peoples from different parts of world relied on traditional medicine for their immediate recovery from COVID-19 and it found effective also. The current research aims to target COVID-19 immunological human host receptors i.e. angiotensin-converting enzyme (ACE)-2, interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha (TNF-α) and protease-activated receptor (PAR)-1 using curcumin derivatives to prevent viral infection and control overproduction of early clinical responses of COVID-19. Targeting these host proteins will mitigate the infection and will filter out many complications caused by these proteins in COVID-19 patients. It is proven through computer-aided computational modeling approaches, total 30 compounds of curcumin and its derivatives were chosen. Drug-likeness parameters were calculated for curcumin and its derivatives and 20 curcumin analogs were selected for docking analysis. From docking analysis of 20 curcumin analogs against five chosen human host receptor targets reveals 11 curcumin analogs possess least binding affinity and best interaction at active sites subjected to absorption, distribution, metabolism, excretion (ADME) analysis. Density functional theory (DFT) analysis of five final shortlisted curcumin derivatives was done to show least binding affinity toward chosen host target protein. Molecular dynamics simulation (MDS) was performed to observe behavior and interaction of potential drug hydrazinocurcumin against target proteins ACE-2 and PAR-1. It was performed at 100 nanoseconds and showed satisfactory results. Finally, our investigation reveals that hydrazinocurcumin possesses immunomodulatory and anti-cytokine therapeutic potential against COVID-19 and it can act as COVID-19 warrior drug molecule and promising choice of drug for COVID-19 treatment, however, it needs further in vivo clinical evaluation to commercialize as COVID-19 drug.Communicated by Ramaswamy H. Sarma.

Genome wide association study and phylogenetic analysis of novel SARS-COV-2 virus among different countries.

Corona Virus (COVID-19) outbreak has threatened the world, since it has become pandemic and spread all over the world. The causative agent SARS-COV2 has proved lethal caused serious public health concern worldwide. Our aims were to describe the SARS-COV-2 genetic connections and check for recombination of all genome. The recombination was investigated by RDP5 and conflicting phylogenetic clustering in individual genomic fragments was established by phylogenetic study by maximum likelihood and Bayesian methods. Our analysis suggests that the available sequences from currently genomes of various strain were retrieved from different countries including Japan, French Republic, Spain, Peru, China, Vietnam, Taiwan, Brazil, U.S.A., South Korea, Sweden, Australia, Nepal, India, Iran, and Italy. The phylogeny of SARS-COV-2 observed the largest number of genome is Vietnam 29891-bp, while France is the smallest member identified with 29679-bp. Using Recombination Detection program5 (RDP5) the china strains was taken as parental strain but there were no recombination in the all strains. In our study we identified the mutation in Pakistani strains in high conserved region of Corona nucleoca super family domain at the nucleotide position (394: C replace with T, Position: 858: C replace with T and Position: 997 G replace A).

Immunoinformatics approaches to explore B and T cell epitope-based vaccine designing for SARS-CoV-2 Virus.

SARS-CoV-2, a new world coronavirus belonging to class Nidovirales of Coronaviridae family causes COVID-19 infection which is the leading cause of death worldwide. Currently there are no approved drugs and vaccines available for the prevention of COVID-19 infection, although couples of immunizations are being tested in clinical trials. However, the present efforts are focused on computational vaccination technique for evaluating candidates to design multi-epitope-based vaccine against pathogenic mechanism of novel SARS-COV-2. Based on recent published evidence, we recognized spike glycoprotein and envelope small membrane protein are the potential targets to combat the pathogenic mechanism of SARS-CoV-2. Similarly, in the present study we identified epitope of both B and T cell associated with these proteins. Extremely antigenic, conserve, immunogenic and nontoxic epitope of B and T cell of Spike protein are WPWYVWLGFI, SRVKNLNSSEGVPDLLV whereas the CWCARPTCIK and YCCNIVNVSL are associated with envelope small membrane protein were selected as potential candidate for vaccine designing. These epitopes show virtuous interaction with HLAA0201 during molecular docking analysis. Under simulation protocol the predicted vaccine candidates show stability. Collectively, this work provides novel potential candidates for epitope-based vaccine designing against COVID-19 infection.

Poly-victimization and mental health of street children in Lahore city.

BACKGROUND: Street children are vulnerable to a number of problems throughout their lives. Poly-victimization covers the different domains of the difficulties they face on streets, it is also notable to find out the impact of poly-victimization on the mental health of street children. AIMS: The purpose of the study was to examine the relationship between poly-victimization and mental health in street children of Lahore city. It was hypothesized that there is likely to be a predictive relationship between poly-victimization and mental health of street children. METHODS: Through purposive sampling a sample of 77 street boys was collected from Lahore city, with the help of three government and private organizations working with street children. Sample included only boys within the age range of 9-13 years (M = 10.66, SD = 1.26) who have been residing on streets for more than one month. Juvenile Victimization Questionnaire and Mental Health Inventory were used for assessment of poly-victimization and mental health respectively. RESULTS: The results indicated that poly-victimization positively predicted the psychological distress and negatively predicted psychological wellbeing in street children. CONCLUSION: The most common type of victimization was conventional crime which negatively predicts mental health of street children. The results have important implications for the policy makers to develop improved services for this vulnerable group.