ABSTRACT
The emerging COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed over six million lives globally to date. Despite the availability of vaccines, the pandemic still cannot be fully controlled owing to rapid mutation of the virus that renders enhanced transmissibility and antibody evasion. This is thus an unmet need to develop safe and effective therapeutic options for COVID-19, in particular, remedies that can be used at home. Considering the great success of multi-targeted cocktail therapy for the treatment of viral infections, metal-based drugs might represent a unique and new source of antivirals that resemble a cocktail therapy in terms of their mode of actions. In this review, we first summarize the role that metal ions played in SARS-CoV-2 viral replication and pathogenesis, then highlight the chemistry of metal-based strategies in the fight against SARS-CoV-2 infection, including both metal displacement and chelation based approaches. Finally, we outline a perspective and direction on how to design and develop metal-based antivirals for the fight against the current or future coronavirus pandemic.