Identification of potential therapeutic targets and mechanisms of COVID-19 through network analysis and screening of chemicals and herbal ingredients.

After experiencing the COVID-19 pandemic, it is widely acknowledged that a rapid drug repurposing method is highly needed. A series of useful drug repurposing tools have been developed based on data-driven modeling and network pharmacology. Based on the disease module, we identified several hub proteins that play important roles in the onset and development of the COVID-19, which are potential targets for repositioning approved drugs. Moreover, different network distance metrics were applied to quantify the relationship between drug targets and COVID-19 disease targets in the protein-protein-interaction (PPI) network and predict COVID-19 therapeutic effects of bioactive herbal ingredients and chemicals. Furthermore, the tentative mechanisms of candidates were illustrated through molecular docking and gene enrichment analysis. We obtained 15 chemical and 15 herbal ingredient candidates and found that different drugs may play different roles in the process of virus invasion and the onset and development of the COVID-19 disease. Given pandemic outbreaks, our method has an undeniable immense advantage in the feasibility analysis of drug repurposing or drug screening, especially in the analysis of herbal ingredients.

The peripheral and core regions of virus-host network of COVID-19.

Two thousand nineteen novel coronavirus SARS-CoV-2, the pathogen of COVID-19, has caused a catastrophic pandemic, which has a profound and widespread impact on human lives and social economy globally. However, the molecular perturbations induced by the SARS-CoV-2 infection remain unknown. In this paper, from the perspective of omnigenic, we analyze the properties of the neighborhood perturbed by SARS-CoV-2 in the human interactome and disclose the peripheral and core regions of virus-host network (VHN). We find that the virus-host proteins (VHPs) form a significantly connected VHN, among which highly perturbed proteins aggregate into an observable core region. The non-core region of VHN forms a large scale but relatively low perturbed periphery. We further validate that the periphery is non-negligible and conducive to identifying comorbidities and detecting drug repurposing candidates for COVID-19. We particularly put forward a flower model for COVID-19, SARS and H1N1 based on their peripheral regions, and the flower model shows more correlations between COVID-19 and other two similar diseases in common functional pathways and candidate drugs. Overall, our periphery-core pattern can not only offer insights into interconnectivity of SARS-CoV-2 VHPs but also facilitate the research on therapeutic drugs.