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.

In silico assessment of potential leads identified from Bauhinia rufescens Lam. as α-glucosidase and α-amylase inhibitors.

INTRODUCTION: Natural products play a pivotal role in innovative drug discovery by providing structural leads for the development of new therapeutic agents against various diseases.The present study aims to focus on the in silico assessment of the therapeutic potential of antidiabetic phytoconstituents which were identified and isolated from the extracts of Bauhinia rufescens Lam, a medicinal plant traditionally used for various pharmacotherapeutic purposes. METHOD: The physicochemical and pharmacokinetic parameters of the previously isolated thirty eight compounds were predicted using SwissADME web tool whereas OSIRIS Property Explorer was used for toxicity risk assessment and drug- likeliness. Twelve compounds were selected for docking on human α-glucosidase and α-amylaseenzymes using Autodock 4.0 software. Furthermore, the active extract was in vivo tested for the antidiabetic activity and then identified usingTLC bioautographic method. RESULTS AND DISCUSSION: Eriodictyol was found to have the highest potential as an inhibitor against α-amylase with binding energy of -9.92 kcal/mol. Rutin was the most potent against α-glucosidase with binding energy of-9.15 kcal/mol. A considerable number of hydrogen bonds and hydrophobic interactions were computed between the compounds and the enzymes thereby making them energetically favorable and suggesting inhibition of these two enzymes as a plausible molecular mechanism for their antidiabetic effect. CONCLUSION: These two flavonoids could therefore be used as potential leads for structure- based design of new effective hypoglycemic agents.

Epitope-Based Peptide Vaccine against Glycoprotein G of Nipah Henipavirus Using Immunoinformatics Approaches.

BACKGROUND: Nipah belongs to the genus Henipavirus and the Paramyxoviridae family. It is an endemic most commonly found at South Asia and has first emerged in Malaysia in 1998. Bats are found to be the main reservoir for this virus, causing disease in both humans and animals. The last outbreak has occurred in May 2018 in Kerala. It is characterized by high pathogenicity and fatality rates which varies from 40% to 70% depending on the severity of the disease and on the availability of adequate healthcare facilities. Currently, there are no antiviral drugs available for NiV disease and the treatment is just supportive. Clinical presentations for this virus range from asymptomatic infection to fatal encephalitis. OBJECTIVE: This study is aimed at predicting an effective epitope-based vaccine against glycoprotein G of Nipah henipavirus, using immunoinformatics approaches. METHODS AND MATERIALS: Glycoprotein G of the Nipah virus sequence was retrieved from NCBI. Different prediction tools were used to analyze the epitopes, namely, BepiPred-2.0: Sequential B Cell Epitope Predictor for B cell and T cell MHC classes II and I. Then, the proposed peptides were docked using Autodock 4.0 software program. Results and Conclusions. The two peptides TVYHCSAVY and FLIDRINWI have showed a very strong binding affinity to MHC class I and MHC class II alleles. Furthermore, considering the conservancy, the affinity, and the population coverage, the peptide FLIDRINWIT is highly suitable to be utilized to formulate a new vaccine against glycoprotein G of Nipah henipavirus. An in vivo study for the proposed peptides is also highly recommended.

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.

Review on the Characteristic, Properties and Analytical Methods of Cefquinomesulphate: ß-lactam Veterinary Drug.

BACKGROUND: Chemotherapy as a science began within the 1st decade of the twentieth century with understanding of the principles of selective toxicity, the particular chemical relationships between microorganism pathogens and medicines, the event of drug resistance, and also the role of combined medical aid. OBJECTIVES: This review aims to highlight the characteristics, specifically the pharmacokinetic parameters and the analytical methods reported in literature for the determination of Cefquinome, a fourth generation cephalosporine used to treat Gram-positive and Gram-negative caused infections. CONCLUSION: Analysis of such drugs, whether used for the treatment of human or animal illness, is essential in understanding the bioavailability and therapeutic control which will ensure their activity and safety.

Development of stability-indicating methods for cefquinome sulphate.

The degradation behavior of cefquinome sulphate in alkaline medium at different temperatures was investigated using both first derivative spectrophotometric and HPLC methods. The drug degradation was found to be pH and temperature dependant. The pH-rate profile indicated a first order dependence of Kobs on [OH(-)] at pHs ranging between 9 and 11. Arrhenius plot obtained at pH 10 was linear between 65° and 100°C. The estimated activation energy of the hydrolysis was found to be 21.1 kcal mol(-1). Stability-indicating thin-layer chromatographic method for the separation of the drug and its alkaline hydrolysis product has been developed.