Metallo therapeutics for COVID-19. Exploiting metal-based compounds for the discovery of new antiviral drugs

Abstract

Introduction: The COVID-19 pandemic poses an unprecedented challenge for the rapid discovery of drugs against this life-threatening disease. Owing to the peculiar features of the metal centers that are currently used in medicinal chemistry, metallodrugs might offer an excellent opportunity to achieve this goal. Areas covered: Two main strategies for developing metal-based drugs against the SARS-CoV-2 are herein illustrated. Firstly, a few clinically approved metallodrugs could be evaluated in patients according to a 'drug repurposing' approach. To this respect, the gold drug auranofin seems a promising candidate, but some other clinically established metal compounds are worthy of a careful evaluation as well. On the other hand, libraries of inorganic compounds, featuring a large chemical diversity, should be screened to identify the most effective molecules. This second strategy might be assisted by a pathway-driven discovery approach arising from a preliminary knowledge of the mode of action, exploitable to inhibit the functional activities of the key viral proteins. Also, attention must be paid to selectivity and toxicity issues. Expert opinion: The medicinal inorganic chemistry community may offer a valuable contribution against COVID-19. The screening of metallodrugs' libraries can expand the explored 'chemical space' and increase the chance of finding effective anti-COVID agents.

Antiviral performance of graphene-based materials with emphasis on COVID-19: A review

“…Metallodrugs such as the gold drug auranofin (2,3,4,6-tetra-o-acetyl-L-thio-β-D-glycol-pyranoses-S-(triethyl-phosphine)-gold(I)) has shown antiviral influences against COVID-19 in vitro [96] . However, the general problems associated with the use of metal compounds is valid here as well, including the systemic toxicity [97] . Based on molecular mechanics-assisted structure-based virtual screening method, Teralı et al [98] reported a list of drug repurposing candidates which can be used as inhibitors of COVID-19.…”

Will Auranofin Become a Golden New Treatment Against COVID-19?

“…Ultimately, this oral therapy could be added to supportive therapies administered to patients under monitoring in hospital settings and could benefit COVID-19 patients with mild to moderate symptoms recovering at home. We therefore join our voices with other researchers (33,49,53,54,62) to encourage the evaluation in animal models and clinical trials of chrysotherapy with auranofin, or possibly other gold metallodrugs, alone or in combination with other immunomodulatory molecules for the treatment of COVID-19.…”

Strategies for the Improvement of Metal-Based Chemotherapeutic Treatments

“…Consequently, two clinical trials involving auranofin for HIV treatment have begun (ClinicalTrials.gov, Identifiers: NCT02961829 and NCT02176135). Furthermore, the antiviral activity of auranofin prompted us to suggest its evaluation for the treatment of COVID-19 infections within the wide drug repositioning program that was initiated to find effective drugs to counter the rapid spread of the pandemic [ 5 , 42 ].…”

“…However, only with the advent of modern medicine in the early 20th century, were metallodrugs first used on a scientific basis for the treatment of several diseases, including bacterial and parasitic infections [ 1 , 3 , 4 ]. More recently, with the rapid improvement of organic synthetic chemistry and the discovery of various organic molecules as effective antibiotics and anticancer agents, the use of metal complexes in medicine has undergone a rapid decrease [ 5 ]. This trend has been further extended due to concerns regarding their systemic toxicity [ 6 ].…”