Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children and causes chronic diarrhea in AIDS patients, but the only approved treatment is ineffective in malnourished children and immunocompromised people. We here use a drug repositioning strategy and identify a promising anticryptosporidial drug candidate. Screening a library of benzoxaboroles comprised of analogs to four antiprotozoal chemical scaffolds under pre-clinical development for neglected tropical diseases for Cryptosporidium growth inhibitors identifies the 6-carboxamide benzoxaborole AN7973. AN7973 blocks intracellular parasite development, appears to be parasiticidal, and potently inhibits the two Cryptosporidium species most relevant to human health, C. parvum and C. hominis . It is efficacious in murine models of both acute and established infection, and in a neonatal dairy calf model of cryptosporidiosis. AN7973 also possesses favorable safety, stability, and PK parameters, and therefore, is an exciting drug candidate for treating cryptosporidiosis.

H7N9, a novel strain of avian origin influenza was the first recorded incidence where a human was transited by a N9 type influenza virus. Effective vaccination against influenza A (H7N9) is a major concern, since it has emerged as a life threatening viral pathogen. Here, an in silico reverse vaccinology strategy was adopted to design a unique chimeric subunit vaccine against avian influenza A (H7N9). Induction of humoral and cell-mediated immunity is the prime concerned characteristics for a peptide vaccine candidate, hence both T cell and B cell immunity of viral proteins were screened. Antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach were adopted to generate the most antigenic epitopes of avian influenza A (H7N9) proteome. Further, a novel subunit vaccine was designed by the combination of highly immunogenic epitopes along with suitable adjuvant and linkers. Physicochemical properties and secondary structure of the designed vaccine were assessed to ensure its thermostability, hydrophilicity, theoretical PI and structural behavior. Homology modeling, refinement and validation of the designed vaccine allowed to construct a three dimensional structure of the predicted vaccine, further employed to molecular docking analysis with different MHC molecules and human immune TLR8 receptor present on lymphocyte cells. Moreover, disulfide engineering was employed to lessen the high mobility region of the designed vaccine in order to extend its stability. Furthermore, we investigated the molecular dynamic simulation of the modeled subunit vaccine and TLR8 complexed molecule to strengthen our prediction. Finally, the suggested vaccine was reverse transcribed and adapted for E. coli strain K12 prior to insertion within pET28a(+) vector for checking translational potency and microbial expression.

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32 33 H7N9, a novel strain of avian origin influenza was the first recorded incidence where a human was 34 transited by a N9 type influenza virus. Effective vaccination against influenza A (H7N9) is a major 35 concern, since it has emerged as a life threatening viral pathogen. Here, an in silico reverse 36 vaccinology strategy was adopted to design a unique chimeric subunit vaccine against avian 37 influenza A (H7N9). Induction of humoral and cell-mediated immunity is the prime concerned 38 characteristics for a peptide vaccine candidate, hence both T cell and B cell immunity of viral 39 proteins were screened. Antigenicity testing, transmembrane topology screening, allergenicity and 40 toxicity assessment, population coverage analysis and molecular docking approach were adopted 41 to generate the most antigenic epitopes of avian influenza A (H7N9) proteome. Further, a novel 42 subunit vaccine was designed by the combination of highly immunogenic epitopes along with 43 suitable adjuvant and linkers. Physicochemical properties and secondary structure of the designed 44 vaccine were assessed to ensure its thermostability, hydrophilicity, theoretical PI and 45 structural behavior. Homology modeling, refinement and validation of the designed vaccine 46 allowed to construct a three dimensional structure of the predicted vaccine, further employed to 47 molecular docking analysis with different MHC molecules and human immune TLR8 receptor 48 present on lymphocyte cells. Moreover, disulfide engineering was employed to lessen the high 49 mobility region of the designed vaccine in order to extend its stability. Furthermore, we 50 investigated the molecular dynamic simulation of the modeled subunit vaccine and TLR8 51 complexed molecule to strengthen our prediction. Finally, the suggested vaccine was reverse 52 transcribed and adapted for E. coli strain K12 prior to insertion within pET28a(+) vector for 53 checking translational potency and microbial expression. 54 55

The novel coronavirus disease 2019 (COVID-19) has unfolded an unprecedented worldwide public health emergency with disastrous economic consequences. Around 96 million coronavirus cases have already been identified with over half a million deaths. Despite numerous efforts by the government as well as international organizations, these numbers are still increasing with a surprising rate. Although urgent and absolutely necessary, a reliable therapeutic or vaccine is still elusive and this status quo may remain for an uncertain period of time. Taken that into account, boosting up adaptive immunity through nutritional interventions may help subside this epidemic and save many lives. This review focuses on the nexus between a balanced diet and adaptive immunity, particularly, how a poor diet may lead to compromised immunity resulting in susceptibility to viral infections. Additionally, we discuss how nutrients (vitamins, minerals, trace elements) can be used as a tool to modulate immune response and thus impede viral infections. The study also summarizes nutritional recommendations to combat COVID-19 in different countries and territories as well as dietary sources of those key nutrients. Moreover, different nutritional intervention strategies based on different age groups, physiological and medical conditions were also included, and the challenges of nutritional interventions towards the care of COVID-19 patients are also discussed. Since the availability of a drug or vaccine is still uncertain, a balanced diet or nutrient therapy can be used as a robust strategy to combat COVID-19. Thus, we hope this review may help to make an informed decision with regard to diet choice both at individual level as well as clinical settings.

Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) cause a variety of infections including oral-facial infections, genital herpes, herpes keratitis, cutaneous infection and so on. To date, FDA-approved licensed HSV vaccine is not available yet. Hence, the study was conducted to identify and characterize an effective epitope based polyvalent vaccine against both types of Herpes Simplex Virus through targeting six viral proteins. The selected proteins were retrieved from viralzone and assessed to design highly antigenic epitopes by binding analyses of the peptides with MHC class-I and class-II molecules, antigenicity screening, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach. The final vaccine was constructed by the combination of top CTL, HTL and BCL epitopes from each protein along with suitable adjuvant and linkers. Physicochemical and secondary structure analysis, disulfide engineering, molecular dynamic simulation and codon adaptation were further employed to develop a unique multi-epitope peptide vaccine. Docking analysis of the refined vaccine structure with different MHC molecules and human immune TLR-2 receptor demonstrated higher interaction. Complexed structure of the modeled vaccine and TLR-2 showed minimal deformability at molecular level. Moreover, translational potency and microbial expression of the modeled vaccine was analyzed with pET28a(+) vector for E. coli strain strain K12. The study enabled design of a novel chimeric polyvalent vaccine to confer broad range immunity against both HSV serotypes. However, further wet lab based research using model animals are highly recommended to experimentally validate our findings.

Marburg virus causes severe hemorrhagic fever in both humans and non-human primates with high degree of infectivity and lethality. To date no approved treatment is available for Marburg virus infection. A study was employed to design a novel chimeric vaccine against Marburg virus by adopting reverse vaccinology approach. Envelope glycoprotein and matrix protein VP40 were identified as most antigenic viral proteins which generated a plethora of antigenic epitopes. Results showed that vaccine construct V1 was superior in terms of various physicochemical properties and structural stability. Molecular docking analysis of the refined vaccine with different MHCs and human immune TLR8 receptor demonstrated higher binding affinity. Moreover, complexed structure of the modeled vaccine and TLR8 indicated minimal deformability at molecular level. Translational potency and microbial expression of the modeled vaccine within E. coli strain K12 by pET28a(+) vector were also biologically significant. However, further in vitro and in vivo investigation could be implemented for the acceptance and validation of the designed vaccine against Marburg virus.

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