Published 20/4 - long paper worth the read to those interested. I have pasted (and highlighted) excerpts I think are relevant to BIT
Novel 2019 Coronavirus Structure, Mechanism of Action,
Antiviral drug promises and rule out against its treatment4- Protein Ion Channel Activity (
https://www.tandfonline.com/doi/full/10.1080/07391102.2020.1758788 )
The COVID-19 E-protein is a short and integral membrane protein that contains 76-109 amino acids, size ranging between 8.4 and 12 kDa, consist of 35 α-helices and 40 loops. The protein has short hydrophilic amino terminus consisting of 7–12 amino acids, followed by a large hydrophobic transmembrane domain of 25 amino acids long hydrophilic C-terminal domain (shown in box). The hydrophobic region can generate oligomerization and form an ion-conductive pore in membranes,
it plays a significant role in the assembly of the viral genome. This protein is involved in several aspects of the virus life cycle, such as assembly, budding, envelope formation, and pathogenesis (Schoeman & Fielding, 2019). E protein’s ion channel activity is found in the transmembrane region of the protein(Verdiá-Báguena et al., 2012; Wilson, Mckinlay, Gage, & Ewart, 2004). The membrane potential has been regulated by E-protein controlling the ion flow between the intracellular and extracellular environment.
The ion conductivity triggered by E-protein via the manipulation of COVID-19 genome seems to be a novel route involved in virus pathogenesis. Although, the E-protein has been interacted with other coronavirus proteins as well as host cell proteins.
E-protein’s ion channel activity and the alteration of coronavirus cell ion balance by E-protein is a necessary process for virus production but the effect of E-protein ion channel activity in virus pathogenesis remains elusive.Few efforts have been found that mutation of the E-protein in the extracellular membrane could disrupt the ion-conductivity and the normal viral assembly (Torres et al., 2007; Verdiá-Báguena et al., 2012),
hence control the E protein dynamics is a promising target for preventing pathogenesis associated with the COVID-19 (Pervushin et al., 2009). For example, Nieto-torres et al., (Nieto-torres et al., 2014)have demonstrated that, Mice infected with COVID-19 viruses exhibited E-protein ion channel activity, with wild-type E-protein sequence, that restored ion transport, resulting in the mice death with the loss of weight. In contrast, mice infected with mutant E-protein showed lack of ion channel activity and has result they recovered from the disease and most survived. This evidence confirmed that ion channel activity correlated well with the virus growth. The strong E-protein ion channel activity is generated a higher chance for the mortality of mice is observed.
Hence, inhibitor target to E-protein process can help to prevent virus production. In this respect, Wilson et al., showed that hexamethylene amiloride inhibitor has shown to block the E-protein ion channel conductance in cell membrane and inhibits replication of the parent coronavirus in cultured cells(Wilson, Gage, &
Ewart, 2006). Recently, Gupta et al., (Gupta et al., 2020) have identified the medicinal properties of Belachinal, Macaflavanone E and Vibsanol B inhibitors which are successfully passed the ADMET test and Lipinski’s rule 5s. These compounds are reduced the random motion of the human COVID-19 E protein in terms of inhibiting the function of the human “COVID-19 E” protein. So far, our understanding about the mechanism of the E-protein ion channel activity in the viral assembly is an ongoing debate.
This is one of the most important research topics to investigated which deals with E-protein ion channel activity in viral production to reduce the mortality rate of diseased human by deletion of E-protein by inhibitor.
8. Conclusion
......... Both the computational and experimental outcomes in terms of novel drugs should be recommended a new drug to test in vivo experiments that may be suitable for the disease patient. Following fundamental knowledge of research is required by using computer simulations
1. To elucidate the role of E-protein ion channel activity in virus pathogenesis by study the E-protein ion conductivity with the manipulation of COVID-19 genome. 2. To identify inhibitor block the E-protein ion channel activity as well as inhibits COVID-19 RNA polymerase.......
The above is pretty much (to my limited knowledge) what BIT have been claiming they are able to do on previous SARS viruses - so hopefully on the right track for positive Covid-19 antiviral results in the very near future.
