The Intricacy of the Viral-Human Protein Interaction Networks: Resources, Data, and Analyses.

Viral infections are one of the major causes of human diseases that cause yearly millions of deaths and seriously threaten global health, as we have experienced with the COVID-19 pandemic. Numerous approaches have been adopted to understand viral diseases and develop pharmacological treatments. Among them, the study of virus-host protein-protein interactions is a powerful strategy to comprehend the molecular mechanisms employed by the virus to infect the host cells and to interact with their components. Experimental protein-protein interactions described in the scientific literature have been systematically captured into several molecular interaction databases. These data are organized in structured formats and can be easily downloaded by users to perform further bioinformatic and network studies. Network analysis of available virus-host interactomes allow us to understand how the host interactome is perturbed upon viral infection and what are the key host proteins targeted by the virus and the main cellular pathways that are subverted. In this review, we give an overview of publicly available viral-human protein-protein interactions resources and the community standards, curation rules and adopted ontologies. A description of the main virus-human interactome available is provided, together with the main network analyses that have been performed. We finally discuss the main limitations and future challenges to assess the quality and reliability of protein-protein interaction datasets and resources.

RNA-protein interactomes as invaluable resources to study RNA viruses: Insights from SARS CoV-2 studies.

Understanding the molecular mechanisms of severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is essential for the successful development of therapeutic strategies against the COVID-19 pandemic. Numerous studies have focused on the identification of host factors and cellular pathways involved in the viral replication cycle. The speed and magnitude of hijacking the translation machinery of host mRNA, and shutting down host transcription are still not well understood. Since SARS-CoV-2 relies on host RNA-binding proteins for the infection progression, several efforts have been made to define the SARS-CoV-2 RNA-bound proteomes (RNA-protein interactomes). Methodologies that enable the systemic capture of protein interactors of given RNA in vivo have been adapted for the identification of the SARS-CoV-2 RNA interactome. The obtained proteomic data aided by genome-wide and targeted CRISPR perturbation screens, revealed host factors with either pro- or anti-viral activity and highlighted cellular processes and factors involved in host response. We focus here on the recent studies on SARS-CoV-2 RNA-protein interactomes, with regard to both the technological aspects of RNA interactome capture methods and the obtained results. We also summarize several related studies, which were used in the interpretation of the SARS-CoV-2 RNA-protein interactomes. These studies provided the selection of host factors that are potentially suitable candidates for antiviral therapy. Finally, we underscore the importance of RNA-protein interactome studies in regard to the effective development of antiviral strategies against current and future threats. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA in Disease and Development > RNA in Disease RNA Methods > RNA Analyses in Cells.

Exploiting the molecular basis of age and gender differences in outcomes of SARS-CoV-2 infections.

Motivation: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease, 2019; COVID-19) is associated with adverse outcomes in patients. It has been observed that lethality seems to be related to the age of patients. While ageing has been extensively demonstrated to be accompanied by some modifications at the gene expression level, a possible link with COVID-19 manifestation still need to be investigated at the molecular level. Objectives: This study aims to shed out light on a possible link between the increased COVID-19 lethality and the molecular changes that occur in elderly people. Methods: We considered public datasets of ageing-related genes and their expression at the tissue level. We selected human proteins interacting with viral ones that are known to be related to the ageing process. Finally, we investigated changes in the expression level of coding genes at the tissue, gender and age level. Results: We observed a significant intersection between some SARS-CoV-2 interactors and ageing-related genes, suggesting that those genes are particularly affected by COVID-19 infection. Our analysis evidenced that virus infection particularly involves ageing molecular mechanisms centred around proteins EEF2, NPM1, HMGA1, HMGA2, APEX1, CHEK1, PRKDC, and GPX4. We found that HMGA1 and NPM1 have different expressions in the lung of males, while HMGA1, APEX1, CHEK1, EEF2, and NPM1 present changes in expression in males due to ageing effects. Conclusion: Our study generated a mechanistic framework to clarify the correlation between COVID-19 incidence in elderly patients and molecular mechanisms of ageing. We also provide testable hypotheses for future investigation and pharmacological solutions tailored to specific age ranges.