Host-pathogen protein-nucleic acid interactions: A comprehensive review

Jain, Anuja; Mittal, Shikha; Tripathi, Lokesh P.; Nussinov, Ruth; Ahmad, Shandar

doi:10.1016/j.csbj.2022.08.001

Cited by 12 publications

(7 citation statements)

References 377 publications

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“…Viral-derived nucleic acids can interact with TLRs, thus, eliciting febrile responses [ 81 ]. In this respect, TLR3 recognizes viral dsRNA, such as reovirus, respiratory syncytial virus, west Nile virus, dengue virus, influenza A virus, Epstein Barr virus and herpes simplex virus [ 82 ]. Conversely, TLR7, TLR8 and TLR9 recognize ssRNA in viruses [ 83 , 84 , 85 ].…”

Section: Fever Of Microbial Originmentioning

confidence: 99%

Microbial and Host Metabolites at the Backstage of Fever: Current Knowledge about the Co-Ordinate Action of Receptors and Molecules Underlying Pathophysiology and Clinical Implications

et al. 2023

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Fever represents an elevation of body temperature, that exerts a protective effect against pathogens. Innate immune cells and neurons are implicated in the regulation of body temperature. Pathogen-associated molecular patterns, i.e., lipopolysaccharides from Gram-negative bacteria and peptidoglycan and lipoteichoic acid from Gram-positive bacteria are exogenous pyrogens, that bind to Toll-like receptors on immune and non-immune cells. The subsequent release of pro-inflammatory cytokines [interleukin-1 (IL-1), IL-6 and Tumor necrosis factor-alpha] and their passage through the brain trigger the febrile response. In fact, neurons of the pre-optic area produce prostaglandin E2 (PGE2), that, in turn, bind to the PGE2 receptors; thus, generating fever. Apart from classical non-steroidal anti-inflammatory drugs, i.e., aspirin and acetaminophen, various botanicals are currently used as antipyretic agents and, therefore, their mechanisms of action will be elucidated.

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Section: Fever Of Microbial Originmentioning

confidence: 99%

Microbial and Host Metabolites at the Backstage of Fever: Current Knowledge about the Co-Ordinate Action of Receptors and Molecules Underlying Pathophysiology and Clinical Implications

et al. 2023

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“…Pathogens can interact with the host through different mediators, such as proteins, metabolites, and nucleic acids (3,4). Pathogenic organisms or their products enter the cytoplasm of a target cell to function, survive and replicate.…”

Section: The Importance Of Predicting and Understanding The Hp Ppismentioning

confidence: 99%

“…HPIs do not only refer to physical interactions of these two parties. It encapsulates the whole spectrum, starting from the population level to the organism level and down to the detailed molecular level, that is, physical interactions of a pathogen protein with host receptors, other proteins, and nucleic acids (1)(2)(3)(4). This makes HPI studies important toward both a better understanding of pathogen invasion and host cell subversion strategies, as well as therapeutic development to abort these processes.…”

Section: Introductionmentioning

confidence: 99%

“…Pro-inflammatory cytokines and growth factors released by senescent cells can induce proliferation in neighboring cells stimulating tumor evolution (6,7). Pathogens frequently interfere with cellular mechanisms of host cells; they cause DNA damage and an imbalance in tumor suppressor/oncogene expression, resulting in cancer development (3,6,7). They can also evolve to mimic a host protein or an available PPI interface in the host.…”

Section: Introductionmentioning

confidence: 99%

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Pathogen-driven cancers from a structural perspective: Targeting host-pathogen protein-protein interactions

Ozdemir

Nussinov²

2023

Front. Oncol.

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Host-pathogen interactions (HPIs) affect and involve multiple mechanisms in both the pathogen and the host. Pathogen interactions disrupt homeostasis in host cells, with their toxins interfering with host mechanisms, resulting in infections, diseases, and disorders, extending from AIDS and COVID-19, to cancer. Studies of the three-dimensional (3D) structures of host-pathogen complexes aim to understand how pathogens interact with their hosts. They also aim to contribute to the development of rational therapeutics, as well as preventive measures. However, structural studies are fraught with challenges toward these aims. This review describes the state-of-the-art in protein-protein interactions (PPIs) between the host and pathogens from the structural standpoint. It discusses computational aspects of predicting these PPIs, including machine learning (ML) and artificial intelligence (AI)-driven, and overviews available computational methods and their challenges. It concludes with examples of how theoretical computational approaches can result in a therapeutic agent with a potential of being used in the clinics, as well as future directions.

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“…Thus, adjuvants can be categorized into inflammatory adjuvants and dendritic cell adjuvants by clear definitions, and the current categorization based on identified and unidentified receptors is merely a historical convenience [ 107 ]. Adjuvants should be defined based on their comprehensive analysis [ 108 , 109 ], molecular interaction and activation of the immune system, especially involving innate immune receptors (PRRs), and it is necessary to evaluate their functional identification, efficacy, and safety separately. It is molecularly understood that adjuvants command dendritic cells to activate the main response, acquired immunity, while the accompanied induction of excessive inflammation and cytokine storms is a separate side response.…”

Section: Perspectivesmentioning

confidence: 99%

Toward Establishing an Ideal Adjuvant for Non-Inflammatory Immune Enhancement

Seya

Tatematsu

Matsumoto

2022

Cells

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The vertebrate immune system functions to eliminate invading foreign nucleic acids and foreign proteins from infectious diseases and malignant tumors. Because pathogens and cancer cells have unique amino acid sequences and motifs (e.g., microbe-associated molecular patterns, MAMPs) that are recognized as “non-self” to the host, immune enhancement is one strategy to eliminate invading cells. MAMPs contain nucleic acids specific or characteristic of the microbe and are potential candidates for immunostimulants or adjuvants. Adjuvants are included in many vaccines and are a way to boost immunity by deliberately administering them along with antigens. Although adjuvants are an important component of vaccines, it is difficult to evaluate their efficacy ex vivo and in vivo on their own (without antigens). In addition, inflammation induced by currently candidate adjuvants may cause adverse events, which is a hurdle to their approval as drugs. In addition, the lack of guidelines for evaluating the safety and efficacy of adjuvants in drug discovery research also makes regulatory approval difficult. Viral double-stranded (ds) RNA mimics have been reported as potent adjuvants, but the safety barrier remains unresolved. Here we present ARNAX, a noninflammatory nucleic acid adjuvant that selectively targets Toll-like receptor 3 (TLR3) in antigen-presenting dendritic cells (APCs) to safely induce antigen cross-presentation and subsequently induce an acquired immune response independent of inflammation. This review discusses the challenges faced in the clinical development of novel adjuvants.

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Host-pathogen protein-nucleic acid interactions: A comprehensive review

Cited by 12 publications

References 377 publications

Microbial and Host Metabolites at the Backstage of Fever: Current Knowledge about the Co-Ordinate Action of Receptors and Molecules Underlying Pathophysiology and Clinical Implications

Microbial and Host Metabolites at the Backstage of Fever: Current Knowledge about the Co-Ordinate Action of Receptors and Molecules Underlying Pathophysiology and Clinical Implications

Pathogen-driven cancers from a structural perspective: Targeting host-pathogen protein-protein interactions

Toward Establishing an Ideal Adjuvant for Non-Inflammatory Immune Enhancement

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