Tolcapone for COVID-19

Coronavirus (CoV) disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has claimed many lives worldwide and is still spreading since December 2019. The 3C-like protease (3CL pro ) and papain-like protease (PL pro ) are essential for maturation of viral polyproteins in SARS-CoV-2 life cycle and thus regarded as key drug targets for the disease.

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.

Context: The whole universe is facing a coronavirus catastrophe, and prompt treatment for the health crisis is primarily significant. The primary way to improve health conditions in this battle is to boost our immunity and alter our diet patterns. A common bulb veggie used to flavor cuisine is garlic. Compounds in the plant that are physiologically active are present, contributing to its pharmacological characteristics. Among several food items with nutritional value and immunity improvement, garlic stood predominant and more resourceful natural antibiotic with a broad spectrum of antiviral potency against diverse viruses. However, earlier reports have depicted its efficacy in the treatment of a variety of viral illnesses. Nonetheless, there is no information on its antiviral activities and underlying molecular mechanisms. Objectives: The bioactive compounds in garlic include organosulfur (allicin and alliin) and flavonoid (quercetin) compounds. These compounds have shown immunomodulatory effects and inhibited attachment of coronavirus to the angiotensin-converting enzyme 2 (ACE2) receptor and the Mpro of SARS-CoV-2. Further, we have discussed the contradictory impacts of garlic used as a preventive measure against the novel coronavirus. Method: The GC/MS analysis revealed 18 active chemicals, including 17 organosulfur compounds in garlic. Using the molecular docking technique, we report for the first time the inhibitory effect of the under-consideration compounds on the host receptor ACE2 protein in the human body, providing a crucial foundation for understanding individual compound coronavirus resistance on the main protease protein of SARS-CoV-2. Allyl disulfide and allyl trisulfide, which make up the majority of the compounds in garlic, exhibit the most potent activity. Results: Conventional medicine has proven its efficiency from ancient times. Currently, our article's prime spotlight was on the activity of Allium sativum on the relegation of viral load and further highlighted artificial intelligence technology to study the attachment of the allicin compound to the SARS-CoV-2 receptor to reveal its efficacy. Conclusions: The COVID-19 pandemic has triggered interest among researchers to conduct future research on molecular docking with clinical trials before releasing salutary remedies against the deadly malady.