Metal-based strategies for the fight against COVID-19

Abstract

Metallodrugs and metal complexes kill SARS-CoV-2 through inhibition of multiple viral proteins/enzymes.

New nickel(ii) Schiff base complexes as potential tools against SARS-CoV-2 Omicron target proteins: an in silico approach

“…23,24 Recently, several researchers expressed interest in molecular targets and metal-based design for the development of effective therapeutics towards SARS-CoV-2 Omicron variants or other emerging viral diseases. 25–27 Many FDA-approved antiviral drugs (ivermectin and levosalbutamol) are under testing in clinical trials to assess their efficacy against SARS-CoV-2. 28 Our recent report on the in silico antivirus activity of Schiff bases and their metal complexes supported the earlier view of their potential binding affinity and interactions with the spike protein of SARS-CoV-2.…”

Hypothesis: Efficacy of early treatments with some NSAIDs in COVID‐19: Might it also depend on their direct and/or indirect zinc chelating ability?

“…Notably, NAC has been shown to protect from endothelial cell damage induced by SARS‐CoV‐2 spike protein in vitro (Lei et al, 2021 ), and both NAC and GSH can inhibit ADAM17 activity (Stolarczyk et al, 2018 ). More importantly, the combination of NAC with a bismuth‐based drug via an oral route exhibits anti‐SARS‐CoV‐2 potency in a hamster model (Li et al, 2022 ). However, only NAC is expected to functionally inhibit ACE2 (Li et al, 2022 ), whereas bismuth might affect ADAM17 activity interfering with its cysteine‐rich domain.…”

“…More importantly, the combination of NAC with a bismuth‐based drug via an oral route exhibits anti‐SARS‐CoV‐2 potency in a hamster model (Li et al, 2022 ). However, only NAC is expected to functionally inhibit ACE2 (Li et al, 2022 ), whereas bismuth might affect ADAM17 activity interfering with its cysteine‐rich domain. Interestingly, NAC treatment works not only against COVID‐19 but also against both zinc fume inhalation eliminating plasma zinc and paracetamol toxicity by replenishing GSH (Brumas et al, 1992 ; Hjortsø et al, 1988 ; Sestili & Fimognari, 2020 ).…”

Overview of Antiviral Drug Therapy for COVID-19: Where Do We Stand?

“…Phase II clinical trials are ongoing to evaluate the efficacy of ebselen (SPI-1005) in mild and severe COVID-19 patients (NCT04484025/NCT04483973). Ebselen is a synthetic organoselenium with a glutathione peroxidase function which exhibits in vitro antiviral activity against SARS-CoV-2 [ 99 , 100 , 101 ]. Iron level alterations are also detected in COVID-19 patients, related to oxidative stress.…”