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ABSTRACTNewcastle disease virus (NDV) typically induces severe illness in poultry and results in significant economic losses for the worldwide poultry sector. NDV, an RNA virus with a single-stranded negative-sense genome, is susceptible to mutation and immune evasion during viral transmission, thus imposing enormous challenges to avian health and poultry production. NDV is composed of six structural proteins and two nonstructural proteins that exert pivotal roles in viral infection and antiviral responses by interacting with host proteins. Nowadays, there is a particular focus on the mechanisms of virus-host protein interactions in NDV research, yet a comprehensive overview of such research is still lacking. Herein, we briefly summarize the mechanisms regarding the effects of virus-host protein interaction on viral infection, pathogenesis, and host immune responses. This review can not only enhance the present comprehension of the mechanism underlying NDV and host interplay, but also furnish a point of reference for the advancement of antiviral measures.

The cellular SFPQ protein is involved in several stages of the HIV-1 life cycle, but the detailed mechanism of its involvement is not yet fully understood. Here, the role of SFPQ in the early stages of HIV-1 replication has been studied. It is found that changes in the intracellular level of SFPQ affect the integration of viral DNA, but not reverse transcription, and SFPQ is a positive factor of integration. A study of the SFPQ interaction with HIV-1 integrase (IN) has revealed two diRGGX 1-4 motifs in the N-terminal region of SFPQ, which are involved in IN binding. Substitution of a single amino acid residue in any of these regions led to a decrease in binding efficiency, while mutations in both motifs almost completely disrupted the SFPQ interaction with IN. The effect of the SFPQ mutants with impaired ability to bind IN on viral replication has been analyzed. Unlike the wild-type protein, the SFPQ mutants did not affect viral integration. This confirms that SFPQ influences the integration stage through direct interaction with IN. Our results indicate that the SFPQ/IN complex can be considered as a potential therapeutic target for the development of new inhibitors of HIV replication. • SFPQ protein positively affect HIV-1 integration due to integrase binding. • SFPQ protein interacts with HIV-1 integrase via its N-terminal domain. • Two diRGGX 1-4 motifs of SFPQ are involved in integrase binding. [ABSTRACT FROM AUTHOR]

The review article conducts an in-depth analysis of information gleaned from a comprehensive literature search across Scopus, Web of Science, and MedLine databases. The focal point of this search revolves around the identification and exploration of the mechanisms orchestrated by host cell factors in the replication cycle of the human immunodeficiency virus (HIV-1, Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1). The article delves into two primary categories of proteins, namely HIV dependence factors (such as CypA, LEDGF, TSG101) and restriction factors (including SERINС5, TRIM5α, APOBEC3G), providing illustrative examples. The current understanding of the functioning mechanisms of these proteins is elucidated, and an evaluation is presented on the potential development of drugs for treating HIV infection. These drugs aim to either inhibit or stimulate the activity of host factors, offering insights into promising avenues for future research and therapeutic advancements.

Background and Aim: Dengue infection is a global issue which is caused by insect transmitted, positive sense single-stranded RNA dengue virus (DENV). Around 50 million cases of dengue infection is being reported per year whereas population at risk of dengue of infection reaches about 2.5 billion in the tropical and subtropical regions of the world. The present study aimed to develop global consensus sequence of dengue NS1 protein and modelling interaction of NS1 with various host proteins of different cellular pathways. Methods: Serotype specific consensus sequences of Dengue NS1 were generated using CLC-Work Bench software. The Consensus sequences of NS1 and Cellular proteins were modelled using Protein Model Portal (PMP). Comparative interaction of NS1 of various dengue serotypes were analyzed by means of Haddock server. The biomolecular complexes of dengue NS1 and various host proteins (PTBP1, NF-kB, TRAF6, PAIP1, SRFBP1, FGB, TCF7L2 and EIF4G1) thus formed were evaluated for interacting residues through Protein Interaction Calculator (PIC). Results: The serotype-specific consensus sequences revealed high degree of conservation among the various NS1 domains of different isolates of same serotype but is more heterogeneous among different serotypes. The docking results demonstrated that most of the host proteins including (PTBP1, NF-kB, TRAF6, PAIP1, SRFBP1, FGB, TCF7L2 and EIF4G1) have comparable affinity for the NS1 of different serotypes despite considerable degree of variability among the serotypes. Analysis of interactive residues demonstrated involvement of different domains of NS1 for interaction with host partners even within the NS1 of different serotypes for a particular host protein. Conclusion: The in silico study revealed that various NS1 domains of different isolates were relatively conserved among different serotypes but highly heterogeneous from serotype to serotypes. The Wing domain of NS1 protein plays a vital role in interaction with the host proteins.

Simple Summary: Research on GP5 protein is of great significance in the diagnosis, prevention, and control of porcine reproductive and respiratory syndrome virus (PRRSV). We summarize its genetic variation, immunity, replication, apoptosis, virulence, interaction with viral protein and host proteins, which provides a theoretical foundation for exploring the PRRSV replication mechanisms and developing new vaccines. Porcine reproductive and respiratory syndrome (PRRS) is an acute, febrile, and highly contagious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). Glycoprotein 5 (GP5) is a glycosylated envelope protein encoded by the PRRSV ORF5, which has good immunogenicity and can induce the body to produce neutralizing antibodies. Therefore, study of GP5 protein is of great significance in the diagnosis, prevention, and control of PRRSV and the development of new vaccines. We reviewed GP5 protein genetic variation, immune function, interaction with viral protein and host proteins, induction of cell apoptosis, and stimulation of neutralizing antibodies. GP5 protein's influence on virus replication and virulence, as well as its use as a target for viral detection and immunization are reviewed. [ABSTRACT FROM AUTHOR]

The emergence of pandemic situations originated from severe acute respiratory syndrome (SARS)‐CoV‐2 and its new variants created worldwide medical emergencies. Due to the non‐availability of efficient drugs and vaccines at these emergency hours, repurposing existing drugs can effectively treat patients critically infected by SARS‐CoV‐2. Finding a suitable repurposing drug with inhibitory efficacy to a host‐protein is challenging. A detailed mechanistic understanding of the kinetics, (dis)association pathways, key protein residues facilitating the entry–exit of the drugs with targets are fundamental in selecting these repurposed drugs. Keeping this target as the goal of the paper, the potential repurposing drugs, Nafamostat, Camostat, Silmitasertib, Valproic acid, and Zotatifin with host‐proteins HDAC2, CSK22, eIF4E2 are studied to elucidate energetics, kinetics, and dissociation pathways. From an ensemble of independent simulations, we observed the presence of single or multiple dissociation pathways with varying host‐proteins‐drug systems and quantitatively estimated the probability of unbinding through these specific pathways. We also explored the crucial gateway residues facilitating these dissociation mechanisms. Interestingly, the residues we obtained for HDAC2 and CSK22 are also involved in the catalytic activity. Our results demonstrate how these potential drugs interact with the host machinery and the specific target residues, showing involvement in the mechanism. Most of these drugs are in the preclinical phase, and some are already being used to treat severe COVID‐19 patients. Hence, the mechanistic insight presented in this study is envisaged to support further findings of clinical studies and eventually develop efficient inhibitors to treat SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

High Temperature Requirement A (HtrA) was identified as a secreted virulence factor in many pathogenic bacteria, including Listeria monocytogenes. Recently, it was discovered that Helicobacter pylori and Campylobacter jejuni HtrAs can directly cleave the human cell-adhesion molecule E-cadherin, which facilitates bacterial transmigration. HtrAs also interact with extracellular matrix (ECM) molecules. However, only a limited number of studies have been carried out in this regard. In the present study, the protease and ECM binding properties of L. monocytogenes HtrA (LmHtrA) were studied using native rLmHtrA, catalytically inactive rLmHtrA(S343A) and rLmHtrA lacking the PDZ domain (∆PDZ) to gain more insights into HtrA–ECM molecule interaction. The results show that (1) native rLmHtrA cleaves fibrinogen, fibronectin, plasminogen and casein in a time and temperature dependent manner, (2) interaction of rLmHtrA with various host proteins was found in the micromolar to nanomolar range, (3) in the absence of PDZ domain, rLmHtrA exhibits no drastic change in binding affinity toward the host molecules when compared with native rLmHtrA and (4) the PDZ domain plays an important role in the substrate cleavage as rLmHtrA1-394∆PDZ cleaves the substrates only under certain conditions. The proteolysis of various ECM molecules by rLmHtrA possibly highlights the role of HtrA in L. monocytogenes pathogenesis involving ECM degradation. [ABSTRACT FROM AUTHOR]

Faecal proteomics targeting biomarkers of immunity and inflammation have demonstrated clinical application for the identification of changes in gastrointestinal function. However, there are limited comprehensive analyses of the host faecal proteome and how it may be influenced by dietary factors. To examine this, the Homo sapiens post-diet proteome of older males was analysed at the completion of a 10-week dietary intervention, either meeting the minimum dietary protein recommendations (RDA; n = 9) or twice the recommended dietary allowance (2RDA, n = 10). The host faecal proteome differed markedly between individuals, with only a small subset of proteins present in ≥ 60% of subjects (14 and 44 proteins, RDA and 2RDA, respectively, with only 7 common to both groups). No differences were observed between the diet groups on the profiles of host faecal proteins. Faecal proteins were detected from a wide range of protein classes, with high inter-individual variation and absence of obvious impact in response to diets with markedly different protein intake. This suggests that well-matched whole food diets with two-fold variation in protein intake maintained for 10 weeks have minimal impact on human faecal host proteins.

Dengue infection is a global issue which is caused by insect transmitted, positive sense single-stranded RNA dengue virus (DENV). Around 50 million cases of dengue infection is being reported per year whereas population at risk of dengue of infection reaches about 2.5 billion in the tropical and subtropical regions of the world. The present study aimed to develop global consensus sequence of dengue NS1 protein and modelling interaction of NS1 with various host proteins of different cellular pathways. Serotype specific consensus sequences of Dengue NS1 were generated using CLC-Work Bench software. The Consensus sequences of NS1 and Cellular proteins were modelled using Protein Model Portal (PMP). Comparative interaction of NS1 of various dengue serotypes were analyzed by means of Haddock server. The biomolecular complexes of dengue NS1 and various host proteins (PTBP1, NF-kB, TRAF6, PAIP1, SRFBP1, FGB, TCF7L2 and EIF4G1) thus formed were evaluated for interacting residues through Protein Interaction Calculator (PIC). The serotype-specific consensus sequences revealed high degree of conservation among the various NS1 domains of different isolates of same serotype but is more heterogeneous among different serotypes. The docking results demonstrated that most of the host proteins including (PTBP1, NF-kB, TRAF6, PAIP1, SRFBP1, FGB, TCF7L2 and EIF4G1) have comparable affinity for the NS1 of different serotypes despite considerable degree of variability among the serotypes. Analysis of interactive residues demonstrated involvement of different domains of NS1 for interaction with host partners even within the NS1 of different serotypes for a particular host protein. The in silico study revealed that various NS1 domains of different isolates were relatively conserved among different serotypes but highly heterogeneous from serotype to serotypes. The Wing domain of NS1 protein plays a vital role in interaction with the host proteins. [ABSTRACT FROM AUTHOR]

Understanding of the construction and function of the HIV capsid has advanced considerably in the last decade. This is due in large part to the development of more sophisticated structural techniques, particularly cryo-electron microscopy (cryoEM) and cryo-electron tomography (cryoET). The capsid is known to be a pleomorphic fullerene cone comprised of capsid protein monomers arranged into 200–250 hexamers and 12 pentamers. The latter of these induce high curvature necessary to close the cone at both ends. CryoEM/cryoET, NMR, and X-ray crystallography have collectively described these interactions to atomic or near-atomic resolutions. Further, these techniques have helped to clarify the role the HIV capsid plays in several parts of the viral life cycle, from reverse transcription to nuclear entry and integration into the host chromosome. This includes visualizing the capsid bound to host factors. Multiple proteins have been shown to interact with the capsid. Cyclophilin A, nucleoporins, and CPSF6 promote viral infectivity, while MxB and Trim5α diminish the viral infectivity. Finally, structural insights into the intra- and intermolecular interactions that govern capsid function have enabled development of small molecules, peptides, and truncated proteins to disrupt or stabilize the capsid to inhibit HIV replication. The most promising of these, GS6207, is now in clinical trial.

The capsid (CA) protein of the human immunodeficiency virus type 1 (HIV-1) is an essential structural component of a virion and facilitates many crucial life cycle steps through interactions with host cell factors. Capsid shields the reverse transcription complex from restriction factors while it enables trafficking to the nucleus by hijacking various adaptor proteins, such as FEZ1 and BICD2. In addition, the capsid facilitates the import and localization of the viral complex in the nucleus through interaction with NUP153, NUP358, TNPO3, and CPSF-6. In the later stages of the HIV-1 life cycle, CA plays an essential role in the maturation step as a constituent of the Gag polyprotein. In the final phase of maturation, Gag is cleaved, and CA is released, allowing for the assembly of CA into a fullerene cone, known as the capsid core. The fullerene cone consists of ~250 CA hexamers and 12 CA pentamers and encloses the viral genome and other essential viral proteins for the next round of infection. As research continues to elucidate the role of CA in the HIV-1 life cycle and the importance of the capsid protein becomes more apparent, CA displays potential as a therapeutic target for the development of HIV-1 inhibitors.

The 14-3-3 proteins are a family of ubiquitous and exclusively eukaryotic proteins with an astoundingly significant number of binding partners. Their binding alters the activity, stability, localization, and phosphorylation state of a target protein. The association of 14-3-3 proteins with the regulation of a wide range of general and specific signaling pathways suggests their crucial role in health and disease. Recent studies have linked 14-3-3 to several RNA and DNA viruses that may contribute to the pathogenesis and progression of infections. Therefore, comprehensive knowledge of host–virus interactions is vital for understanding the viral life cycle and developing effective therapeutic strategies. Moreover, pharmaceutical research is already moving towards targeting host proteins in the control of virus pathogenesis. As such, targeting the right host protein to interrupt host–virus interactions could be an effective therapeutic strategy. In this review, we generated a 14-3-3 protein interactions roadmap in viruses, using the freely available Virusmentha network, an online virus–virus or virus–host interaction tool. Furthermore, we summarize the role of the 14-3-3 family in RNA and DNA viruses. The participation of 14-3-3 in viral infections underlines its significance as a key regulator for the expression of host and viral proteins.

Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV−) and co-infected (HIV+) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV− individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV+ individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV− TB, 0.95 for HIV+ TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB.

Viruses hijack the host cell machinery and recruit host proteins to aid their replication. Several host proteins also play vital roles in inhibiting viral replication. Emerging class of host proteins central to both of these processes are the DEAD-box helicases: a highly conserved family of ATP-dependent RNA helicases, bearing a common D-E-A-D (Asp-Glu-Ala-Asp) motif. They play key roles in numerous cellular processes, including transcription, splicing, miRNA biogenesis and translation. Though their sequences are highly conserved, these helicases have quite diverse roles in the cell. Interestingly, often these helicases display contradictory actions in terms of the support and/or clearance of invading viruses. Increasing evidence highlights the importance of these enzymes, however, little is known about the structural basis of viral RNA recognition by the members of the DEAD-box family. This review summarizes the current knowledge in the field for selected DEAD-box helicases and highlights their diverse actions upon viral invasion of the host cell. We anticipate that through a better understanding of how these helicases are being utilized by viral RNAs and proteins to aid viral replication, it will be possible to address the urgent need to develop novel therapeutic approaches to combat viral infections. [ABSTRACT FROM AUTHOR]

Lentiviral vectors (LVs) have been successfully used in clinical trials showing long term therapeutic benefits. Studying the role of cellular proteins in lentivirus HIV-1 life cycle can help understand virus assembly and budding, leading to improvement of LV production for gene therapy. Lentiviral vectors were purified using size exclusion chromatography (SEC). The cellular protein composition of LVs produced by two different methods was compared: the transient transfection system pseudotyped with the VSV-G envelope, currently used in clinical trials, and a stable producer cell system using a non-toxic envelope derived from cat endogenous retrovirus RD114, RDpro. Proteins of LVs purified by size exclusion chromatography were identified by tandem mass spectrometry (MS/MS). A smaller number of cellular protein species were detected in stably produced vectors compared to transiently produced vector samples. This may be due to the presence of co-purified VSV-G vesicles in transiently produced vectors. AHNAK (Desmoyokin) was unique to RDpro-Env vectors. The potential role in LV particle production of selected proteins identified by MS analysis including AHNAK was assessed using shRNA gene knockdown technique. Down-regulation of the selected host proteins AHNAK, ALIX, and TSG101 in vector producer cells did not result in a significant difference in vector production. [ABSTRACT FROM AUTHOR]

The human ATPase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3X) emerged as a novel therapeutic target in the fight against both infectious diseases and cancer. Herein, a new family of DDX3X inhibitors was designed, synthesized, and tested for its inhibitory action on the ATPase activity of the enzyme. The potential use of the most promising derivatives it has been investigated by evaluating their anti-HIV-1 effects, revealing inhibitory activities in the low micromolar range. A preliminary ADME analysis demonstrated high metabolic stability and good aqueous solubility. The promising biological profile, together with the suitable in vitro pharmacokinetic properties, make these novel compounds a very good starting point for further development.

After invasion of a susceptible target cell, HIV-1 completes the early phase of its life cycle upon integration of reverse-transcribed viral DNA into host chromatin. The viral capsid, a conical shell encasing the viral ribonucleoprotein complex, along with its constitutive capsid protein, plays essential roles at virtually every step in the early phase of the viral life cycle. Recent work has begun to reveal how the viral capsid interacts with specific cellular proteins to promote these processes. At the same time, cellular restriction factors target the viral capsid to thwart infection. Comprehensive understanding of capsid–host interactions that promote or impede HIV-1 infection may provide unique insight to exploit for novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Retroviral integration is an essential stage in the life cycle of retroviruses. Viruses need to insert their DNA into the chromosomal DNA of the host cells. Retroviral integration is a complex process which involves viral and host proteins and requires the movement of the retroviral DNA from the cytoplasm to the nucleus. The viral integrase is a key enzyme in this process that catalyzes two reactions: 3´ processing of viral DNA that take place in the cytoplasm following reverse transcription and the strand transfer that inserts viral DNA in a host cell chromosome. Development of a successful treatment for the human immunodeficiency virus (HIV) infection using the strand transfer inhibitor, Raltegravir, has demonstrated that retroviral integration is a suitable step for drug intervention. Different types of inhibitors targeting HIV integrase or any of the other components of the retroviral integration process are currently being designed or developed. This work contains a summary of the retroviral integration process as well as, many of the latest advances in this topic which were exposed at the recently held IVth International Meeting on Retroviral Integration.

The cylindrical inclusion (CI) protein of potyviruses is involved in virus replication and cell-to-cell movement. These two processes should rely on multiple plant-virus interactions; however, little is known about the host factors that are involved in, or that may interfere with, CI functions. By using a yeast two-hybrid system, the CI protein from Plum pox virus (PPV) was found to interact with the photosystem I PSI-K protein, the product of the gene psaK, of Nicotiana benthamiana. Coexpression of PPV CI was shown to cause a decrease in the accumulation level of PSI-K transiently expressed in N. benthamiana leaves. To test the biological relevance of this interaction, we have analyzed the infection of PPV in N. benthamiana plants in which psaK gene expression has been silenced by RNA interference, as well as in Arabidopsis thaliana psaK knockout plants. Our results show that downregulation of the psaK gene leads to higher PPV accumulation, suggesting a role for the CI-PSI-K interaction in PPV infection.

The movement of potexviruses through the cytoplasm to plasmodesmata (PD) and through PD to adjacent cells depends on the viral and host cellular proteins. Potexviruses encode three movement proteins (referred to as the triple gene block or TGB1–3). TGB1 protein moves cell-to-cell through PD and requires TGB2 and TGB3, which are endoplasmic reticulum (ER)-located proteins. TGB3 protein directs the movement of the ER-derived vesicles induced by TGB2 protein from the perinuclear ER to the cortical ER. TGB2 protein physically interacts with TGB3 protein in a membrane-associated form and also interacts with either CP or TGB1 protein at the ER network. Recent studies indicate that potexvirus movement involves the interaction between TGB proteins and CP with host proteins including membrane rafts. A group of host cellular membrane raft proteins, remorins (REMs), can serve as a counteracting membrane platform for viral RNP docking and can thereby inhibit viral movement. The CP, which is a component of the RNP movement complex, is also critical for viral cell-to-cell movement through the PD. Interactions between TGB1 protein and/or the CP subunit with the 5'-terminus of genomic RNA (vRNA) form RNP movement complexes and direct the movement of viral RNAs through the PD. Recent studies show that tobacco proteins such as NbMPB2C or NbDnaJ-like proteins interact with the stem-loop 1 RNA located at the 5'-terminus of PVX vRNA and regulate intracellular as well as intercellular movement. Although several host proteins that interact with vRNAs or viral proteins and that are crucial for vRNA transport have been screened and characterized, additional host proteins and details of viral movement remain to be characterized. In this review, we describe recent progress in understanding potexvirus movement within and between cells and how such movement is affected by interactions between viral RNA/proteins and host proteins.

Herpesviruses are highly prevalent viruses associated with numerous pathologies both in animal and human populations. Until now, most of the strategies used to prevent or to cure these infections have been unsuccessful because these viruses have developed numerous immune evasion mechanisms. Therefore, a better understanding of their complex lifecycle is needed. In particular, while the genome of numerous herpesviruses has been sequenced, the exact composition of virions remains unknown for most of them. Mass spectrometry has recently emerged as a central method and has permitted fundamental discoveries in virology. Here, we review mass spectrometry-based approaches that have recently allowed a better understanding of the composition of the herpesvirus virion. In particular, we describe strategies commonly used for proper sample preparation and fractionation to allow protein localization inside the particle but also to avoid contamination by nonstructural proteins. A collection of other important data regarding post-translationalmodifications or the relative abundance of structural proteins is also described. This review also discusses the poorly studied importance of host proteins in herpesvirus structural proteins and the necessity to develop a quantitative workflow to better understand the dynamics of the structural proteome. In the future, we hope that this collaborative effort will assist in the development of new strategies to fight these infections. [ABSTRACT FROM AUTHOR]

Host proteins are the integral part of a successful infection caused by a given RNA virus pathogenic to plants. Therefore, identification of crucial host proteins playing an important role in establishing the infection process is likely to help in devising approaches to curbing disease spread. Cucumber mosaic virus (Q-CMV) and its satellite RNA (QsatRNA) are important pathogens of many economically important crop plants worldwide. In a previous study, we demonstrated the biological significance of a Bromodomain containing RNA-binding Protein (BRP1) in the infection cycle of QsatRNA, making BRP1 an important host protein to study. To further shed a light on the mechanistic role of BRP1 in the replication of Q-CMV and QsatRNA, we analyzed the Nicotiana benthamiana host protein interactomes either for BRP1 alone or in the presence of Q-CMV or QsatRNA. Co-immunoprecipitation, followed by LC–MS/MS analysis of BRP1-FLAG on challenging with Q-CMV or QsatRNA has led us to observe a shift in the host protein interactome of BRP1. We discuss the significance of these results in relation to Q-CMV and its QsatRNA infection cycle. Biological significance Host proteins play an important role in replication and infection of eukaryotic cells by a wide-range of RNA viruses pathogenic to humans, animals and plants. Since a given eukaryotic cell typically contains ~ 30,000 different proteins, recent advances made in proteomics and bioinformatics approaches allowed the identification of host proteins critical for viral replication and pathogenesis. Although Cucumber mosaic virus (CMV) and its satRNA are well characterized at molecular level, information concerning the network of host factors involved in their replication and pathogenesis is still on its infancy. We have recently observed that a Bromodomain containing host protein (BRP1) is obligatory to transport satRNA to the nucleus. Consequently, it is imperative to apply proteomics and bioinformatics approaches in deciphering how host interactome network regulates the replication of CMV and its satRNA. In this study, first we established the importance of BRP1 in CMV replication. Then, application of co-immunoprecipitation in conjunction with LC–MS/MS allowed the identification of a wide range of host proteins that are associated with the replication of CMV and its satRNA. Interestingly, a shift in the plant proteome was observed when plants infected with CMV were challenged with its satRNA. [ABSTRACT FROM AUTHOR]

Viruses significantly impact global health because they are the leading cause of death everywhere they are found. Despite the rapid development of human healthcare, more effective viricidal or antiviral therapies must be developed. The need to find safe, novel, and effective alternatives against viral diseases is heightened by the rapid emergence of resistance to, and the high cost of, synthetic antiviral drug(s). The development of novel multi-target antiviral compounds that affect multiple steps of the viral life cycle and host proteins has benefited tremendously from looking to nature for guidance and inspiration. Hundreds of natural molecules are preferred over synthetic drugs because of concerns regarding efficacy and safety and a high resistance rate to conventional therapies. In addition, naturally occurring antiviral agents have demonstrated reasonable antiviral value in both animal and human studies. Therefore, finding new antiviral drugs is crucial, and natural products provide an excellent opportunity. This brief review examines the evidence of antiviral effects exhibited by various plants and herbs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Pigeon paramyxovirus type 1 (PPMV-1) belongs to the avian paramyxovirus type 1 group of viruses, which can cause tremors, torticollis, and respiratory signs in domestic and wild pigeons. The M protein of PPMV-1 is a multifunctional structural protein. It not only helps in the assembly, budding, and positioning of the virus but also inhibits the host's immune response and promotes replication of the virus in the host. In this study, the GST pull-down method was used to screen host proteins that interact with PPMV-1 M protein, and then mass spectrometry (MS) was used to analyse the screened host proteins. Enrichment analysis of the differentially expressed genes showed that the 77 screened proteins were highly associated with the gene ontology categories: protein synthesis, metabolism, and cell signalling pathway transduction. We selected NIMA-related kinase 7 (NEK7) as the candidate protein for co-localization analysis and co-immunoprecipitation verification. The results revealed that PPMV-1 M protein interacts with NEK7 of the host cell. This interactome study of PPMV-1 M protein will serve to clarify its function during viral replication and will provide a crucial theoretical basis for studying the pathogenic mechanism of PPMV-1. • GST pull-down identified 77 endogenous proteins that interact with PPMV-1 M protein. • The M proteins of the three strains can participate in viral replication by interaction with host factors. • The M protein/NEK interaction is one of the pathogenic mechanisms of PPMV-1. [ABSTRACT FROM AUTHOR]

Rhabdoviridae, characterized by bullet-shaped viruses, is known for its diverse host range, which includes plants, arthropods, fishes and humans. Understanding the viral-host interactions of this family can prove beneficial in developing effective therapeutic strategies. The host proteins interacting with animal rhabdoviruses have been reviewed in this report. Several important host proteins commonly interacting with animal rhabdoviruses are being reported, some of which, interestingly, have molecular features, which can serve as potential antiviral targets. This review not only provides the generalized importance of the functions of animal rhabdovirus-associated host proteins for the first time but also compares them among the two most studied viruses, i.e. Rabies virus (RV) and Vesicular Stomatitis virus (VSV). The comparative data can be used for studying emerging viruses such as Chandipura virus (CHPV) and the lesser studied viruses such as Piry virus (PIRYV) and Isfahan virus (ISFV) of the Rhabdoviridae family. [ABSTRACT FROM AUTHOR]

Retroviral integration is an essential stage in the life cycle of retroviruses. Viruses need to insert their DNA into the chromosomal DNA of the host cells. Retroviral integration is a complex process which involves viral and host proteins and requires the movement of the retroviral DNA from the cytoplasm to the nucleus. The viral integrase is a key enzyme in this process that catalyzes two reactions: 3' processing of viral DNA that take place in the cytoplasm following reverse transcription and the strand transfer that inserts viral DNA in a host cell chromosome. Development of a successful treatment for the human immunodeficiency virus (HIV) infection using the strand transfer inhibitor, Raltegravir, has demonstrated that retroviral integration is a suitable step for drug intervention. Different types of inhibitors targeting HIV integrase or any of the other components of the retroviral integration process are currently being designed or developed. This work contains a of the retroviral integration process as well as, many of the latest advances in this topic which were exposed at the recently held IVth International Meeting on Retroviral Integration. [ABSTRACT FROM AUTHOR]

Abstract: Cysteine peptidases have potent activities in the pathogenesis of various parasitic infections, and are considered as targets for chemotherapy and antigens for vaccine. In this study, two cathepsin B-like cysteine peptidases (EmCBP1 and EmCBP2) from Echinococcus multilocularis metacestodes were identified and characterized. Immunoblot analyses demonstrated that EmCBP1 and EmCBP2 were present in excretory/secretory products and extracts of E. multilocularis metacestodes. By immunohistochemistry, EmCBP1 and EmCBP2 were shown to localize to the germinal layer, the brood capsule and the protoscolex. Recombinant EmCBP1 and EmCBP2 expressed in Pichia pastoris, at optimum pH 5.5, exhibited substrate preferences for Z-Phe-Arg-MCA, Z-Val-Val-Arg-MCA, and Z-Leu-Arg-MCA, and low levels of hydrolysis of Z-Arg-Arg-MCA. Furthermore, recombinant enzymes degraded IgG, albumin, type I and IV collagens, and fibronectin. These results suggested that EmCBP1 and EmCBP2 may play key roles in protein digestion for parasites’ nutrition and in parasite–host interactions. [Copyright &y& Elsevier]

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Since the onset of global pandemic, the most focused research currently in progress is the development of potential drug candidates and clinical trials of existing FDA approved drugs for other relevant diseases, in order to repurpose them for the COVID-19. At the same time, several high throughput screenings of drugs have been reported to inhibit the viral components during the early course of infection but with little proven efficacies. Here, we investigate the drug repurposing strategies to counteract the coronavirus infection which involves several potential targetable host proteins involved in viral replication and disease progression. We report the high throughput analysis of literature-derived repurposing drug candidates that can be used to target the genetic regulators known to interact with viral proteins based on experimental and interactome studies. In this work we have performed integrated molecular docking followed by molecular dynamics (MD) simulations and free energy calculations through an expedite in silico process where the number of screened candidates reduces sequentially at every step based on physicochemical interactions. We elucidate that in addition to the pre-clinical and FDA approved drugs that targets specific regulatory proteins, a range of chemical compounds (Nafamostat, Chloramphenicol, Ponatinib) binds to the other gene transcription and translation regulatory proteins with higher affinity and may harbour potential for therapeutic uses. There is a rapid growing interest in the development of combination therapy for COVID-19 to target multiple enzymes/pathways. Our in silico approach would be useful in generating leads for experimental screening for rapid drug repurposing against SARS-CoV-2 interacting host proteins.Communicated by Ramaswamy H. Sarma.

The capsid (CA) protein of the human immunodeficiency virus type 1 (HIV-1) is an essential structural component of a virion and facilitates many crucial life cycle steps through interactions with host cell factors. Capsid shields the reverse transcription complex from restriction factors while it enables trafficking to the nucleus by hijacking various adaptor proteins, such as FEZ1 and BICD2. In addition, the capsid facilitates the import and localization of the viral complex in the nucleus through interaction with NUP153, NUP358, TNPO3, and CPSF-6. In the later stages of the HIV-1 life cycle, CA plays an essential role in the maturation step as a constituent of the Gag polyprotein. In the final phase of maturation, Gag is cleaved, and CA is released, allowing for the assembly of CA into a fullerene cone, known as the capsid core. The fullerene cone consists of ~250 CA hexamers and 12 CA pentamers and encloses the viral genome and other essential viral proteins for the next round of infection. As research continues to elucidate the role of CA in the HIV-1 life cycle and the importance of the capsid protein becomes more apparent, CA displays potential as a therapeutic target for the development of HIV-1 inhibitors. [ABSTRACT FROM AUTHOR]

Understanding of the construction and function of the HIV capsid has advanced considerably in the last decade. This is due in large part to the development of more sophisticated structural techniques, particularly cryo-electron microscopy (cryoEM) and cryo-electron tomography (cryoET). The capsid is known to be a pleomorphic fullerene cone comprised of capsid protein monomers arranged into 200–250 hexamers and 12 pentamers. The latter of these induce high curvature necessary to close the cone at both ends. CryoEM/cryoET, NMR, and X-ray crystallography have collectively described these interactions to atomic or near-atomic resolutions. Further, these techniques have helped to clarify the role the HIV capsid plays in several parts of the viral life cycle, from reverse transcription to nuclear entry and integration into the host chromosome. This includes visualizing the capsid bound to host factors. Multiple proteins have been shown to interact with the capsid. Cyclophilin A, nucleoporins, and CPSF6 promote viral infectivity, while MxB and Trim5α diminish the viral infectivity. Finally, structural insights into the intra- and intermolecular interactions that govern capsid function have enabled development of small molecules, peptides, and truncated proteins to disrupt or stabilize the capsid to inhibit HIV replication. The most promising of these, GS6207, is now in clinical trial. [ABSTRACT FROM AUTHOR]

The 14-3-3 proteins are a family of ubiquitous and exclusively eukaryotic proteins with an astoundingly significant number of binding partners. Their binding alters the activity, stability, localization, and phosphorylation state of a target protein. The association of 14-3-3 proteins with the regulation of a wide range of general and specific signaling pathways suggests their crucial role in health and disease. Recent studies have linked 14-3-3 to several RNA and DNA viruses that may contribute to the pathogenesis and progression of infections. Therefore, comprehensive knowledge of host–virus interactions is vital for understanding the viral life cycle and developing effective therapeutic strategies. Moreover, pharmaceutical research is already moving towards targeting host proteins in the control of virus pathogenesis. As such, targeting the right host protein to interrupt host–virus interactions could be an effective therapeutic strategy. In this review, we generated a 14-3-3 protein interactions roadmap in viruses, using the freely available Virusmentha network, an online virus–virus or virus–host interaction tool. Furthermore, we summarize the role of the 14-3-3 family in RNA and DNA viruses. The participation of 14-3-3 in viral infections underlines its significance as a key regulator for the expression of host and viral proteins. [ABSTRACT FROM AUTHOR]

The human ATPase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3X) emerged as a novel therapeutic target in the fight against both infectious diseases and cancer. Herein, a new family of DDX3X inhibitors was designed, synthesized, and tested for its inhibitory action on the ATPase activity of the enzyme. The potential use of the most promising derivatives it has been investigated by evaluating their anti-HIV-1 effects, revealing inhibitory activities in the low micromolar range. A preliminary ADME analysis demonstrated high metabolic stability and good aqueous solubility. The promising biological profile, together with the suitable in vitro pharmacokinetic properties, make these novel compounds a very good starting point for further development. [ABSTRACT FROM AUTHOR]

During the study of host-parasite relationships in taeniid parasite diseases, including cysticercosis and hydatidosis, reports have described the presence of host proteins in the cyst fluid and tissue of metacestodes. However, the fate or role of host elements inside the parasite remains barely explored. After the publication of genomes of four cestode species, it became clear that these organisms possess a limited biosynthetic capability. The initial goal of the present study was to determine if uptaken host proteins could be a source of essential amino acids for cysticerci. To track the utilization of uptaken proteins, we added metabolically labeled IgG- 3 H and GFP- 3 H to the culture medium of Taenia crassiceps cysticerci. Incorporation of labeled amino acid was evaluated by fluorography in cysticerci extracts. Our results showed that the use of uptaken proteins by cysticerci as a source of amino acids appeared negligible. Exploring alternative fates for the host proteins, proteomic analysis of the protein matrix in calcareous corpuscles was carried out. Since T. crassiceps does not contain calcareous corpuscles, proteomic analyses were performed in corpuscles of Taenia solium cysticerci. Our results demonstrated that host proteins represented approximately 70% of protein content in the calcareous corpuscles. The presence of the two major uptaken host proteins, namely albumin and IgG, was also demonstrated by Western blot in the matrix of corpuscles. Our findings strongly suggested that the uptake and disposal of host proteins involve calcareous corpuscles, expanding the physiological role of these mineral concretions to a far more important level than previously proposed., (© 2018 The Author(s).)