Emerging viruses, such as filoviruses (Ebola, Marburg), SARS and MERS coronaviruses, and Zika, pose significant threats to global public health, particularly for individuals with co-morbidities. To address these challenges, this review article explores multidisciplinary strategies for combatting emerging viruses. We emphasize the importance of developing accurate diagnostics, innovative therapeutic gene and vaccine delivery systems, and long-acting nanotherapeutics. These approaches are designed to enhance the safety and efficacy of treatments against these deadly pathogens. We discuss the collaborative efforts of virologists, geneticists, formulation scientists, clinicians, immunologists, and medicinal chemists in advancing these therapeutic modalities.

Papaya ringspot virus (PRSV) is one of the most devastating viruses of papaya that has significantly hampered papaya production across the globe. Although PRSV resistance is known in some of its wild relatives, such as Vasconcellea cauliflora and in some of the improved papaya genotypes, the molecular basis of this resistance mechanism has not been studied and understood. Plant microRNAs are an important class of small RNAs that regulate the gene expression in several plant species against the invading plant pathogens. These miRNAs are known to manifest the expression of genes involved in resistance against plant pathogens, through modulation of the plant\'s biochemistry and physiology. In this study we made an attempt to study the overall expression pattern of small RNAs and more specifically the miRNAs in different papaya genotypes from India, that exhibit varying levels of tolerance or resistance to PRSV. Our study found that the expression of some of the miRNAs was differentially regulated in these papaya genotypes and they had entirely different miRNA expression profile in healthy and PRSV infected symptomatic plants. This data may help in improvement of papaya cultivars for resistance against PRSV through new breeding initiatives or biotechnological approaches such as genome editing.

Low levels of high-density lipoprotein (HDL) and impaired HDL functionality have been consistently associated with increased susceptibility to infection and its serious consequences. This has been attributed to the critical role of HDL in maintaining cellular lipid homeostasis, which is essential for the proper functioning of immune and structural cells. HDL, a multifunctional particle, exerts pleiotropic effects in host defense against pathogens. It functions as a natural nanoparticle, capable of sequestering and neutralizing potentially harmful substances like bacterial lipopolysaccharides. HDL possesses antiviral activity, preventing viruses from entering or fusing with host cells, thereby halting their replication cycle. Understanding the complex relationship between HDL and the immune system may reveal innovative targets for developing new treatments to combat infectious diseases and improve patient outcomes. This review aims to emphasize the role of HDL in influencing the course of bacterial and viral infections and its and its therapeutic potential.

In this review, we explore how pseudotyped viruses (PVs) are being applied to the study of viruses affecting both humans and horses. For the purposes of this review, we define PVs as non-replicative viruses with the core of one virus and the surface protein(s) of another and encapsulating a reporter gene such as luciferase. These \'reporter\' PVs enable receptor-mediated entry into host cells to be quantified, and thus can be applied to study the initial stages of viral replication. They can also be used to test antiviral activity of compounds and measure envelope protein-specific antibodies in neutralisation tests.

SUMMARYUnderstanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the mechanism(s) of action of chemical microbicides commonly used in infection prevention and control. Contrary to the typical site-specific mode of action of antibiotics, microbicides often act via multiple targets, causing rapid and irreversible damage to microbes. In the case of viruses, the envelope or protein capsid is usually the primary structural target, resulting in loss of envelope integrity or denaturation of proteins in the capsid, causing loss of the receptor-binding domain for host cell receptors, and/or breakdown of other viral proteins or nucleic acids. However, for certain virucidal microbicides, the nucleic acid may be a significant site of action. The region of primary damage to the protein or nucleic acid is site-specific and may vary with the virus type. Due to their greater complexity and metabolism, bacteria and fungi offer more targets. The rapid and irreversible damage to microbes may result from solubilization of lipid components and denaturation of enzymes involved in the transport of nutrients. Formulation of microbicidal actives that attack multiple sites on microbes, or control of the pH, addition of preservatives or potentiators, and so on, can increase the spectrum of action against pathogens and reduce both the concentrations and times needed to achieve microbicidal activity against the target pathogens.

Clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 virus was detected in the South American sea lions found dead in Santa Catarina, Brazil, in October 2023. Whole genome sequencing and comparative phylogenetic analysis were conducted to investigate the origin, genetic diversity, and zoonotic potentials of the H5N1 viruses. The H5N1 viruses belonged to the genotype B3.2 of clade 2.3.4.4b H5N1 virus, which was identified in North America and disseminated to South America. They have acquired new amino acid substitutions related to mammalian host affinity. Our study provides insights into the genetic landscape of HPAI H5N1 viruses in Brazil, highlighting the continuous evolutionary processes contributing to their possible adaptation to mammalian hosts.

Many pathogens enter the host through mucosal sites. Thus, interfering with pathogen entry through local neutralization at mucosal sites therefore is an effective strategy for preventing disease. Mucosally administered vaccines have the potential to induce protective immune responses at mucosal sites. This manuscript delves into some of the latest developments in mucosal vaccination, particularly focusing on advancements in adjuvant technologies and the role of these adjuvants in enhancing vaccine efficacy against respiratory pathogens. It highlights the anatomical and immunological complexities of the respiratory mucosal immune system, emphasizing the significance of mucosal secretory IgA and tissue-resident memory T cells in local immune responses. We further discuss the differences between immune responses induced through traditional parenteral vaccination approaches vs. mucosal administration strategies, and explore the protective advantages offered by immunization through mucosal routes.

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is an enveloped DNA virus of the Baculoviridae family. This baculovirus is widely exploited for the biological control of insect pest species and as an expression platform to produce recombinant proteins in insect cells. Extracellular vesicles (EVs) are secreted by all cells and are involved in key roles in many biological processes through their cargo consisting of proteins, RNA or DNA. In viral infections, EVs have been found to transfer both viral and cellular cargo that can elicit either a pro- or antiviral response in recipient cells. Here, small EVs (sEVs) released by Spodoptera frugiperda (Sf) insect cells were characterised for the first time. Using S. frugiperda (SfC1B5) cells stably expressing the baculovirus gp64, the viral envelope protein GP64 was shown to be incorporated into sEVs. Sf9 cells were also transfected with a bacmid AcMNPV genome lacking p6.9 (AcΔP6.9) to prevent budded virus production. The protein content of sEVs from both mock- and AcΔP6.9-transfected cells were analysed by mass spectrometry. In addition to GP64, viral proteins Ac-F, ME-53 and viral ubiquitin were identified, as well as many host proteins including TSG101-which may be useful as a protein marker for sEVs.

The 14-3-3 family of proteins are highly conserved acidic eukaryotic proteins (25-32 kDa) abundantly present in the body. Through numerous binding partners, the 14-3-3 is responsible for many essential cellular pathways, such as cell cycle regulation and gene transcription control. Hence, its dysregulation has been linked to the onset of critical illnesses such as cancers, neurodegenerative diseases and viral infections. Interestingly, explorative studies have revealed an inverse correlation of 14-3-3 protein in cancer and neurodegenerative diseases, and the direct manipulation of 14-3-3 by virus to enhance infection capacity has dramatically extended its significance. Of these, COVID-19 has been linked to the 14-3-3 proteins by the interference of the SARS-CoV-2 nucleocapsid (N) protein during virion assembly. Given its predisposition towards multiple essential host signalling pathways, it is vital to understand the holistic interactions between the 14-3-3 protein to unravel its potential therapeutic unit in the future. As such, the general structure and properties of the 14-3-3 family of proteins, as well as their known biological functions and implications in cancer, neurodegeneration, and viruses, were covered in this review. Furthermore, the potential therapeutic target of 14-3-3 proteins in the associated diseases was discussed.

The proteins of Nipah virus ascribe to its lifecycle and are crucial to infections caused by the virus. In the absence of approved therapeutics, these proteins can be considered as drug targets. This study examined the potential of fifty-three (53) natural compounds to inhibit Nipah virus fusion glycoprotein (NiV F) and matrix protein (NiV M) in silico. The molecular docking experiment, supported by the principal component analysis (PCA), showed that out of all the phytochemicals considered, Tribulusamide B had the highest inhibitory potential against the target proteins NiV F and NiV M (-9.21 and -8.66 kcal mol-1, respectively), when compared to the control drug, Ribavirin (-7.01 and -6.52 kcal mol-1, respectively). Furthermore, it was found that Tribulusamide B pharmacophores, namely, hydrogen donors, acceptors, aromatic and hydrophobic groups, contributed towards the effective residual interactions with the target proteins. The molecular dynamic simulation further validated the results of the docking studies and concluded that Tribulusamide B formed a stable complex with the target proteins. The data obtained from MM-PBSA study further explained that the phytochemical could strongly bind with NiV F (-31.26 kJ mol-1) and NiV M (-40.26 kJ mol-1) proteins in comparison with the control drug Ribavirin (-13.12 and -13.94 kJ mol-1, respectively). Finally, the results indicated that Tribulusamide B, a common inhibitor effective against multiple proteins, can be considered a potential therapeutic entity in treating the Nipah virus infection.