Morphine for COVID-19

Background:The development and roll-out of vaccines, and the use of various drugs have contributed to controlling the COVID-19 pandemic. Nevertheless, challenges such as the inequitable distribution of vaccines, the influence of emerging viral lineages and immune evasive variants on vaccine efficacy, and the inadequate immune defense in subgroups of the population continue to motivate the development of new drugs to combat the disease. Aim:In this study, we sought to identify, prioritize, and characterize drug repurposing candidates appropriate for treating mild, moderate, or severe COVID-19 using a network-based integrative approach that systematically integrates drug-related data and multi-omics datasets. Methods: We leveraged drug data, and multi-omics data, and used a random walk restart algorithm to explore an integrated knowledge graph comprised of three sub-graphs: (i) a COVID-19 knowledge graph, (ii) a drug repurposing knowledge graph, and (iii) a COVID-19 disease-state specific omics graph. Results:We prioritized twenty FDA-approved agents as potential candidate drugs for mild, moderate, and severe COVID-19 disease phases. Specifically, drugs that could stimulate immune cell recruitment and activation including histamine, curcumin, and paclitaxel have potential utility in mild disease states to mitigate disease progression. Drugs like omacetaxine, crizotinib, and vorinostat that exhibit antiviral properties and have the potential to inhibit viral replication can be considered for mild to moderate COVID-19 disease states. Also, given the association between antioxidant deficiency and high inflammatory factors that trigger cytokine storms, antioxidants like glutathione can be considered for moderate disease states. Drugs that exhibit potent anti-inflammatory effects like (i) anti-inflammatory drugs (sarilumab and tocilizumab), (ii) corticosteroids (dexamethasone and hydrocortisone), and (iii) immunosuppressives (sirolimus and cyclosporine) are potential candidates for moderate to severe disease states that trigger a hyperinflammatory cascade of COVID-19. Conclusion:Our study demonstrates that the multi-omics data-driven integrative analysis within the drug data enables prioritizing drug candidates for COVID-19 disease phases, offering a comprehensive basis for therapeutic strategies that can be brought to market quickly given their established safety profiles. Importantly, the multi-omics data-driven integrative analysis within the drug data approach implemented here can be used to prioritize drug repurposing candidates appropriate for other diseases.

ABSTRACT The COVID 19 pandemic is an outbreak caused by the coronavirus disease 2019 (COVID-19) with clinical manifestations of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which has caused a large number of deaths worldwide. The most common complications of COVID-19 are cardiovascular and kidney disorders. The urgency to develop natural medicines with natural ingredients that are effective against COVID-19 is very important to maintain body immunity and at the same time protect the body from close contact with sufferers of COVID-19. Moringa plants have the potential to increase the body's resistance (immune booster) of sufferers against SARS-CoV-2. (COVID-19) and moringa plants have other health functions such as anti-inflammatory, antimicrobial, antidiabetic, antioxidant, antitumor, anticancer, antihypertensive, antiasthma, anticoagulation, antiurolithiasis, anthelmintic, antifertility, antihyperthyroid, and antialzheimer's. Several components of Moringa that play a role in the antiviral COVID-19 are Kaempferol, Pterygospermin, Morphine, Quercetin, and Apigenin-7-O-rutinoside. This Literature Review provides a basis for further research on the development of clinical applications of Moringa Oleifera for the treatment of SARS-CoV-2. Keywords: Covid-19, Potential Effects, Literature Review ABSTRAK Pandemi COVID 19 adalah wabah yang disebabkan penyakit coronavirus 2019 (COVID-19) dengan manisfestasi klinis sindrom pernapasan akut coronavirus 2 (SARS-CoV-2) yang menyebabkan kematian yang cukup besar di seluruh dunia. Komplikasi tersering COVID-19 adalah gangguan kardiovaskular dan ginjal. Urgensi mengembangkan pengobatan natural bahan alam yang mempunyai efektivitas terhadap COVID 19 menjadi sangat penting untuk menjaga imunitas tubuh dan sekaligus menjaga tubuh terhadap kontak erat penderita COVID 19. Tanaman kelor mempunyai potensi meningkatkan daya tahan tubuh (booster imun )penderita terhadap penyakit SARS-CoV-2 (COVID 19) dan tanaman kelor memiliki fungsi Kesehatan lainnya seperti antiradang, antimikroba, antidiabetes, antioksidan, antitumor, antikanker, antihipertensi, antiasma, antikoagulasi, antiurolitiasis, anthelmintik, antifertilitas, antihipertiroid, dan antialzheimer. Beberapa komponen kelor yang berperan pada antivirus COVID-19 adalah Kaempferol, Pterygospermin, Morfin, Quercetin, dan Apigenin-7-O-rutinoside. Tinjauan Pustaka ini memberikan dasar untuk penelitian lebih lanjut pengembangan aplikasi klinis Moringa Oleifera untuk pengobatan SARS-CoV-2. Kata Kunci: Covid-19, Efek Potensial, Tinjauan Pustaka

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.