Oh, isn't it Ironic due to the FDA… Ranitidine bismuth citrate showed promise in killing the SARScoronavirus (2003) why was it removed by the FDA in 2019?
In November 2019, the FDA stated that their tests have found levels of NDMA in ranitidine and nizatidine that are similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats.[72][73]
These data suggest that bismuth-based drugs should be evaluated in vivo for the treatment of SARS infections.
One of the most obvious targets is the RNA-dependent RNA polymerase (Nsp12) that produces genome- and subgenome-sized RNAs of both polarities [44,45]. The zinc ionophore, pyrithione, when in combination with ZnOAc2, inhibited SARS-CoV replication in Vero E6 cells, even at a high multiplicity of infection of 4, EC50 of 0.5 µM and with a SI of 164 [46]. The combination of the ionophore-promoting uptake of zinc into cells plus exogenously added zinc increased the intracellular Zn2+ concentrations to levels that presumably inhibited RNA synthesis. This postulate was supported by the fact that ZnOAc2 was shown to inhibit RNA transcription in SARS-CoV transcription complexes and SARS-CoV RNA polymerase activity in an RNA-dependent RNA polymerase assay [46]. In both cases, adding the Zn2+ chelator Mg-ethylenediaminetetraacetic acid abrogated the inhibition. This study provides an interesting mechanism to study the function of the Nsp12 protein, and perhaps it provides basic data that could enable the development of zinc ionophores as antiviral agents, although one might expect such an approach to be fraught with difficulties because of the global effects on host homeostasis [47].
Nonstructural protein 13 is a 5′–3′ helicase with associated NTPase and RNA 5′-tri-phosphatase activities [48–50]. Bismuth compounds have been shown to inhibit SARS-CoV replication [51,52]. Ranitidine bismuth citrate was found to be a good inhibitor of the ATPase activity of the SARS-CoV helicase protein, with an IC50 value of 0.3 µM. FRET-based assays demonstrated inhibition of the DNA duplex unwinding activity with an IC50 value of 0.6 µM. These data were fitted to the logistic equation to give an EC50 value of 5.9 µM for viable SARS-CoV. Expressing this by using a logarithmic scale for cell viability, the compound was relatively nontoxic with a CC50 of 5 mM. Thus, the SI of the compound was 847. In addition, a 90% effective concentration (EC90) was determined and was equal to 50 µM. These data suggest that bismuth-based drugs should be evaluated in vivo for the treatment of SARS infections.
https://pubs.rsc.org/en/content/articlelanding/2007/cc/b709515e#!divAbstract
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136164/
https://en.wikipedia.org/wiki/Ranitidine