I repost this free paper which I posted just 2 days ago because IMO it explains why PBT2 will possibly help the Coronapatients. The paper is theoretical and difficult for most of us. But the result and conclusion are easy for us: PBT2 could be helpful because it increases Zn-levels. Many of us take zinc tablets when getting flu symptoms and so this theory is already in everyday practice for some of us. The proof with Coronavirus may be on the way if ATHE has started the in vitro studies with this new virus. Today we know only that Sinclair is likely active in this Corona fight, but ATH has not told anything yet. So if ATH is active in this issue, it is only doing preliminary investigations. If the results are favorable, we will for sure get some new info about the clinical studies planned.
Here is the abstract
:Zn(2+) Inhibits Coronavirus and Arterivirus RNA Polymerase Activity in Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture
Affiliations
- PMID: 21079686
- PMCID: PMC2973827
- DOI: 10.1371/journal.ppat.1001176
Abstract
Increasing the intracellular Zn(2+) concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. For some viruses this effect has been attributed to interference with viral polyprotein processing. In this study we demonstrate that the combination of Zn(2+) and PT at low concentrations (2 µM Zn(2+) and 2 µM PT) inhibits the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture. The RNA synthesis of these two distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase (RdRp), which is the core enzyme of their multiprotein replication and transcription complex (RTC). Using an activity assay for RTCs isolated from cells infected with SARS-CoV or EAV--thus eliminating the need for PT to transport Zn(2+) across the plasma membrane--we show that Zn(2+) efficiently inhibits the RNA-synthesizing activity of the RTCs of both viruses. Enzymatic studies using recombinant RdRps (SARS-CoV nsp12 and EAV nsp9) purified from E. coli subsequently revealed that Zn(2+) directly inhibited the in vitro activity of both nidovirus polymerases. More specifically, Zn(2+) was found to block the initiation step of EAV RNA synthesis, whereas in the case of the SARS-CoV RdRp elongation was inhibited and template binding reduced. By chelating Zn(2+) with MgEDTA, the inhibitory effect of the divalent cation could be reversed, which provides a novel experimental tool for in vitro studies of the molecular details of nidovirus replication and transcription.
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