Copper for COVID-19

The World Health Organization has classified the coronavirus disease outbreak as a worldwide pandemic as a result of the COVID-19 expansion. According to medical professionals, individuals with strong immunity often outlive infections more frequently than those with poor immunity. The COVID-19 pandemic has prompted the need for novel approaches to treating the illness and its symptoms. Natural products from plants are increasingly being seen favorably in comparison to synthetic ones in the fight against diseases. As a result, in order to avoid contracting any unanticipated illnesses, individuals must increase their immunity by eating more dietary supplements and by taking drugs that have immune-boosting properties. This review aimed to give a general overview of some traditional Sudanese foods and drinks that are rich in immune-boosting elements, and accordingly, they could be safely recommended as an adjuvant dietary supplement to improve the immune system's ability to fight such infections as COVID-19. Also, this review aims to bring attention to the fact that immune boosters may be found in natural sources, which will help pharmaceutical companies by taking some of the load off of them. Electronic databases, including Google Scholar, Scopus, and the Web of Science, were searched for relevant material. The selected articles underwent independent eligibility and information extraction reviews. The review focused on certain traditional Sudanese herbs and their derivatives that are rich in immune-stimulating vitamins and minerals and therefore could possibly be recommended as immune-boosting dietary supplements to help fight COVID-19. This review highlights the fact that the pharmaceutical sector, especially community and hospital pharmacists, could play a vital role in supporting the healthcare system by encouraging their communities to add plants and their products that are rich in immune-boosting vitamins and minerals to their diet.

Abstract Background The active pursuit of network medicine for drug repurposing, particularly for combating Covid-19, has stimulated interest in the concept of structural controllability in cellular networks. We sought to extend this theory, focusing on the defense rather than control of the cell against viral infections. Accordingly, we extended structural controllability to total structural controllability and introduced the concept of control hubs. Perturbing any control hub may render the cell uncontrollable by exogenous stimuli like viral infections, so control hubs are ideal drug targets. Results We developed an efficient algorithm to identify all control hubs, applying it to a largest homogeneous network of human protein interactions, including interactions between human and SARS-CoV-2 proteins. Our method recognized 65 druggable control hubs with enriched antiviral functions. Utilizing these hubs, we categorized potential drugs into four groups: antiviral and anti-inflammatory agents, drugs acting on the central nervous system, dietary supplements, and compounds enhancing immunity. An exemplification of our approach’s effectiveness, Fostamatinib, a drug initially developed for chronic immune thrombocytopenia, is now in clinical trials for treating Covid-19. Preclinical trial data demonstrated that Fostamatinib could reduce mortality rates, ICU stay length, and disease severity in Covid-19 patients. Conclusions Our findings confirm the efficacy of our novel strategy that leverages control hubs as drug targets. This approach provides insights into the molecular mechanisms of potential therapeutics for Covid-19, making it a valuable tool for interpretable drug discovery. Our new approach is general and applicable to repurposing drugs for other diseases.

Network medicine has been pursued for Covid-19 drug repurposing. One such approach adopts structural controllability, a theory for controlling a network (the cell). Motivated to protect the cell from viral infections, we extended this theory to total controllability and introduced a new concept of control hubs. Perturbation to any control hub renders the cell uncontrollable by exogenous stimuli, e.g., viral infections, so control hubs are ideal drug targets. We developed an efficient algorithm for finding all control hubs and applied it to the largest homogenous human protein-protein interaction network. Our new method outperforms several popular gene-selection methods, including that based on structural controllability. The final 65 druggable control hubs are enriched with functions of cell proliferation, regulation of apoptosis, and responses to cellular stress and nutrient levels, revealing critical pathways induced by SARS-CoV-2. These druggable control hubs led to drugs in 4 major categories: antiviral and anti-inflammatory agents, drugs on central nerve systems, and dietary supplements and hormones that boost immunity. Their functions also provided deep insights into the therapeutic mechanisms of the drugs for Covid-19 therapy, making the new approach an explainable drug repurposing method. A remarkable example is Fostamatinib that has been shown to lower mortality, shorten the length of ICU stay, and reduce disease severity of hospitalized Covid-19 patients. The drug targets 10 control hubs, 9 of which are kinases that play key roles in cell differentiation and programmed death. One such kinase is RIPK1 that directly interacts with viral protein nsp12, the RdRp of the virus. The study produced many control hubs that were not targets of existing drugs but were enriched with proteins on membranes and the NF-$κ$B pathway, so are excellent candidate targets for new drugs.