Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology.

The need for preparing new strategies for the design of emergency drug therapies against COVID-19 and similar diseases in the future is rather urgent, considering the high rate of morbidity and especially mortality associated with COVID-19, which so far has exceeded 18 million lives. Such strategies could be conceived by targeting the causes and also the serious toxic side effects of the diseases, as well as associated biochemical and physiological pathways. Deferiprone (L1) is an EMA- and FDA-approved drug used worldwide for the treatment of iron overload and also other conditions where there are no effective treatments. The multi-potent effects and high safety record of L1 in iron loaded and non-iron loaded categories of patients suggests that L1 could be developed as a "magic bullet" drug against COVID-19 and diseases of similar symptomatology. The mode of action of L1 includes antiviral, antimicrobial, antioxidant, anti-hypoxic and anti-ferroptotic effects, iron buffering interactions with transferrin, iron mobilizing effects from ferritin, macrophages and other cells involved in the immune response and hyperinflammation, as well as many other therapeutic interventions. Similarly, several pharmacological and other characteristics of L1, including extensive tissue distribution and low cost of production, increase the prospect of worldwide availability, as well as many other therapeutic approach strategies involving drug combinations, adjuvant therapies and disease prevention.

Questioning Established Theories and Treatment Methods Related to Iron and Other Metal Metabolic Changes, Affecting All Major Diseases and Billions of Patients.

The medical and scientific literature is dominated by highly cited historical theories and findings [...].

The need for a multi-level drug targeting strategy to curb the COVID-19 pandemic.

Thousands of drugs, nutraceuticals and their combinations can be used to select candidate therapeutics for targeting SARS-CoV-2 and its symptoms in order to curb COVID-19. A comprehensive, multi-level strategy against COVID-19 should include drug targeting of biomolecules and biochemical pathways involved in the prevention and proliferation of the infection, and the fatal or serious symptoms following infection. Several drugs are routinely used in the treatment of different categories of seriously ill COVID-19 patients including tocilizumab, remdesivir and dexamethasone. The current risk/benefit assessment supports the emergency testing and approval of more drugs. The process for new drug selection could be based on the identification of one drug for one target, or of a multi-potent drug for many targets and drug combinations for one or more targets, that can cause a substantial reduction in the high mortality rate of COVID-19. Several drugs have been identified that can fit this potential role by targeting different stages of COVID-19 including baricitinib, molnupiravir and PF-07321332/ritonavir and also the combination of deferiprone with N-acetylcysteine for inhibiting the vicious circle of oxidative stress toxicity and endothelial cell damage. Most of these drugs are expected to be effective against all the SARS-CoV-2 variants including Omicron (B.1.1.529) and also the associated COVID-19 complications.

Conventional and Unconventional Approaches for Innovative Drug Treatments in COVID-19: Looking Outside of Plato's Cave.

Thousands of drugs and nutraceuticals along with their combinations can be used to select candidate therapeutics for targeting the transmission, proliferation and the fatal or severe symptoms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to reduce the unacceptably high mortality rate observed in the coronavirus disease 2019 (COVID-19) pandemic and its associated negative effects on daily life worldwide [...].