The reemergence of dengue virus in Sudan.

Dengue fever (DF) is a mosquito-transmitted arboviral disease caused by 1 of 4 closely related but antigenically distinct serotypes of dengue virus (DENV), DENV-1-4. The primary vector of DENV is Aedes aegypti and Aedes albopictus mosquitoes. Humans are the main carrier of the virus and the amplifying host with non-human primates plays a considerable role in sylvatic cycle. On November 8, 2022, an outbreak of dengue fever has killed at least five people in North Kordofan State. On 23 Nov 2022, the Sudanese Ministry of Health reported 3326 cases of dengue fever across 8 Sudanese States; while 23 patients died from the fever. Sudan is witnessing its worst outbreak of dengue fever in over a decade, especially in North and South Kordofan and Red Sea State are hit hard. In this review, we will focus on the recent outbreak of dengue fever in many Sudanese states.

Novel multi epitope-based vaccine against monkeypox virus: vaccinomic approach.

While mankind is still dealing with the COVID-19 pandemic, a case of monkeypox virus (MPXV) has been reported to the WHO on May 7, 2022. Monkeypox is a viral zoonotic disease that has been a public health threat, particularly in Africa. However, it has recently expanded to other parts of the world, so it may soon become a global issue. Thus, the current work was planned and then designed a multi-epitope vaccine against MPXV utilizing the cell surface-binding protein as a target in order to develop a novel and safe vaccine that can evoke the desirable immunological response. The proposed MHC-I, MHC-II, and B-cell epitopes were selected to design multi-epitope vaccine constructs linked with suitable linkers in combination with different adjuvants to enhance the immune responses for the vaccine constructs. The proposed vaccine was composed of 275 amino acids and was shown to be antigenic in Vaxijen server (0.5311) and non-allergenic in AllerTop server. The 3D structure of the designed vaccine was predicted, refined and validated by various in silico tools to assess the stability of the vaccine. Moreover, the solubility of the vaccine construct was found greater than the average solubility provided by protein-Sol server which indicating the solubility of the vaccine construct. Additionally, the most promising epitopes bound to MHC I and MHC II alleles were found having good binding affinities with low energies ranging between - 7.0 and - 8.6 kcal/mol. According to the immunological simulation research, the vaccine was found to elicit a particular immune reaction against the monkeypox virus. Finally, the molecular dynamic study shows that the designed vaccine is stable with minimum RMSF against MHC I allele. We conclude from our research that the cell surface-binding protein is one of the primary proteins involved in MPXV pathogenesis. As a result, our study will aid in the development of appropriate therapeutics and prompt the development of future vaccines against MPXV.

SHERLOCK and DETECTR: CRISPR-Cas Systems as Potential Rapid Diagnostic Tools for Emerging Infectious Diseases.

Infectious diseases are one of the most intimidating threats to human race, responsible for an immense burden of disabilities and deaths. Rapid diagnosis and treatment of infectious diseases offers a better understanding of their pathogenesis. According to the World Health Organization, the ideal approach for detecting foreign pathogens should be rapid, specific, sensitive, instrument-free, and cost-effective. Nucleic acid pathogen detection methods, typically PCR, have numerous limitations, such as highly sophisticated equipment requirements, reagents, and trained personnel relying on well-established laboratories, besides being time-consuming. Thus, there is a crucial need to develop novel nucleic acid detection tools that are rapid, specific, sensitive, and cost-effective, particularly ones that can be used for versatile point-of-care diagnostic applications. Two new methods exploit unpredicted in vitro properties of CRISPR-Cas effectors, turning activated nucleases into basic amplifiers of a specific nucleic acid binding event. These effectors can be attached to a diversity of reporters and utilized in tandem with isothermal amplification approaches to create sensitive identification in multiple deployable field formats. Although still in their beginning, SHERLOCK and DETECTR technologies are potential methods for rapid detection and identification of infectious diseases, with ultrasensitive tests that do not require complicated processing. This review describes SHERLOCK and DETECTR technologies and assesses their properties, functions, and prospective to become the ultimate diagnostic tools for diagnosing infectious diseases and curbing disease outbreaks.

Immunoinformatics design of multiepitopes peptide-based universal cancer vaccine using matrix metalloproteinase-9 protein as a target.

A new approach toward cancer therapy is the use of cancer vaccine, yet the different molecular bases of cancers, reduce the effectiveness of this approach. In this article, we aim to use matrix metalloproteinase-9 protein (MMP9) which is an essential molecule in the survival and metastasis of all types of cancers as a target for universal cancer vaccine design. The reference sequence of MMP9 protein was obtained from NCBI databases. Furthermore, the B-cell and T cell-related peptides were analyzed using the IEDB website and other related soft wares. The best candidate peptides were then visualized using chimera software. Three peptides were found to be good candidates for interactions with B cells (SLPE, RLYT, and PALPR), while 10 peptides were found as good targets for interactions with MHC1 and another 10 peptides founded suitable for interactions with MHC2 with population coverages of 94.77 and 90.67%, respectively. Finally, the immune response simulation and molecular docking were done using the C-IMMSIM simulator and AutoDock Vina to confirm the effectiveness of the proposed vaccine. By the end of this project: twenty-three peptide-based vaccine was designed for use as a universal cancer vaccine which has a high world population coverage for MHC1 (94.77%) and MHC2 (90.67%) related alleles.

Cytokine Storm in COVID-19 Patients, Its Impact on Organs and Potential Treatment by QTY Code-Designed Detergent-Free Chemokine Receptors.

The novel coronavirus is not only causing respiratory problems, but it may also damage the heart, kidneys, liver, and other organs; in Wuhan, 14 to 30% of COVID-19 patients have lost their kidney function and now require either dialysis or kidney transplants. The novel coronavirus gains entry into humans by targeting the ACE2 receptor that found on lung cells, which destroy human lungs through cytokine storms, and this leads to hyperinflammation, forcing the immune cells to destroy healthy cells. This is why some COVID-19 patients need intensive care. The inflammatory chemicals released during COVID-19 infection cause the liver to produce proteins that defend the body from infections. However, these proteins can cause blood clotting, which can clog blood vessels in the heart and other organs; as a result, the organs are deprived of oxygen and nutrients which could ultimately lead to multiorgan failure and consequent progression to acute lung injury, acute respiratory distress syndrome, and often death. However, there are novel protein modification tools called the QTY code, which are similar in their structure to antibodies, which could provide a solution to excess cytokines. These synthetic proteins can be injected into the body to bind the excess cytokines created by the cytokine storm; this will eventually remove the excessive cytokines and inhibit the severe symptoms caused by the COVID-19 infection. In this review, we will focus on cytokine storm in COVID-19 patients, their impact on the body organs, and the potential treatment by QTY code-designed detergent-free chemokine receptors.

Design of a Multiepitope-Based Peptide Vaccine against the E Protein of Human COVID-19: An Immunoinformatics Approach.

BACKGROUND: A new endemic disease has spread across Wuhan City, China, in December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a "public-health emergency of international concern" due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus, the objective of this study is to design a multiepitope peptide vaccine against COVID-19 using an immunoinformatics approach. METHOD: Several techniques facilitating the combination of the immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the envelope protein of 2019-nCoV as a target. RESULTS: Extensive mutations, insertion, and deletion were discovered with comparative sequencing in the COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively. CONCLUSION: The T-cell epitope-based peptide vaccine was designed for COVID-19 using the envelope protein as an immunogenic target. Nevertheless, the proposed vaccine rapidly needs to be validated clinically in order to ensure its safety and immunogenic profile to help stop this epidemic before it leads to devastating global outbreaks.

Extensive In Silico Analysis of ATL1 Gene : Discovered Five Mutations That May Cause Hereditary Spastic Paraplegia Type 3A.

BACKGROUND: Hereditary spastic paraplegia type 3A (SPG3A) is a neurodegenerative disease inherited type of Hereditary spastic paraplegia (HSP). It is the second most frequent type of HSP which is characterized by progressive bilateral and mostly symmetric spasticity and weakness of the legs. SPG3A gene mutations and the phenotype-genotype correlations have not yet been recognized. The aim of this work was to categorize the most damaging SNPs in ATL1 gene and to predict their impact on the functional and structural levels by several computational analysis tools. METHODS: The raw data of ATL1 gene were retrieved from dbSNP database and then run into numerous computational analysis tools. Additionally; we submitted the common six deleterious outcomes from the previous functional analysis tools to I-mutant 3.0 and MUPro, respectively, to investigate their effect on the structural level. The 3D structure of ATL1 was predicted by RaptorX and modeled using UCSF Chimera to compare the differences between the native and the mutant amino acids. RESULTS: Five nsSNPs out of 249 were classified as the most deleterious (rs746927118, rs979765709, rs119476049, rs864622269, and rs1242753115). CONCLUSIONS: In this study, the impact of nsSNPs in the ATL1 gene was investigated by various in silico tools that revealed five nsSNPs (V67F, T120I, R217Q, R495W, and G504E) are deleterious SNPs, which have a functional impact on ATL1 protein and, therefore, can be used as genomic biomarkers specifically before 4 years of age; also, it may play a key role in pharmacogenomics by evaluating drug response for this disabling disease.

Genetic variations of ND5 gene of mtDNA in populations of Anopheles sinensis (Diptera: Culicidae) malaria vector in China.

BACKGROUND: Anopheles sinensis is a principal vector for Plasmodium vivax malaria in most parts of China. Understanding of genetic structure and genetic differentiation of the mosquito should contribute to the vector control and malaria elimination in China. METHODS: The present study investigated the genetic structure of An. sinensis populations using a 729 bp fragment of mtDNA ND5 among 10 populations collected from seven provinces in China. RESULTS: ND5 was polymorphic by single mutations within three groups of An. sinensis that were collected from 10 different geographic populations in China. Out of 140 specimens collected from 10 representative sites, 84 haplotypes and 71 variable positions were determined. The overall level of genetic differentiation of An. sinensis varied from low to moderate across China and with a FST range of 0.00065-0.341. Genealogy analysis clustered the populations of An. sinensis into three main clusters. Each cluster shared one main haplotype. Pairwise variations within populations were higher (68.68%) than among populations (31.32%) and with high fixation index (FST = 0.313). The results of the present study support population growth and expansion in the An. sinensis populations from China. Three clusters of An. sinensis populations were detected in this study with each displaying different proportion patterns over seven Chinese provinces. No correlation between genetic and geographic distance was detected in overall populations of An. sinensis (R2 = 0.058; P = 0.301). CONCLUSIONS: The results indicate that the ND5 gene of mtDNA is highly polymorphic in An. sinensis and has moderate genetic variability in the populations of this mosquito in China. Demographic and spatial results support evidence of expansion in An. sinensis populations.