Here are a few ideas and thoughts I put together as a pharmacologist on possible theoretic interventions and theoretical mechanisms of action of drugs against #Covid_19.
Thread.
Thread.
Coronavirus virus particles contain FOUR main structural proteins. These are the spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins. Targeting any of these proteins with drugs will be a potential pharmacological intervention. 
The initial attachment of the virion to the host cell is initiated by interactions between the S protein and its receptor.
This S-protein/receptor interaction is the primary determinant for a coronavirus to infect a host species and also governs the tissue tropism of the virus.
This S-protein/receptor interaction is the primary determinant for a coronavirus to infect a host species and also governs the tissue tropism of the virus.
Following receptor binding, the virus must next gain access to the host cell cytosol. This is possible with viral protease enzyme, followed by fusion of the viral and cellular membranes. Therefore, a coronavirus specific protease inhibitor is an attractive pharmacological option.
The next step in the coronavirus lifecycle is the translation of the replicase gene from the viral genomic RNA.
So a replicase inhibitor is another drug option. However, in pharmacology, replicase inhibitors USUALLY have LOWER genetic barrier to resistance vs protease inhibitors.
So a replicase inhibitor is another drug option. However, in pharmacology, replicase inhibitors USUALLY have LOWER genetic barrier to resistance vs protease inhibitors.
Viral RNA synthesis follows the translation and assembly of the viral replicase complexes. Viral RNA synthesis produces both genomic and sub-genomic RNAs.
Following replication and subgenomic RNA synthesis, the viral structural proteins, S, E, and M are translated and inserted into the endoplasmic reticulum (ER).
The M protein directs most protein-protein interactions required for assembly of mature coronaviruses.
The M protein directs most protein-protein interactions required for assembly of mature coronaviruses.
Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.
The S protein mediates cell-cell fusion between infected cells and uninfected cells. This leads to the formation of giant, multinucleated cells, which allows the virus to spread within an infected organism without being detected or neutralized by virus-specific antibodies.
Thus, M or S protein analogs are theoretically other options for pharmacological intervention, but this will probably require the drugs to be biological in nature (i.e monoclonal antibodies -mAbs), which is not easy (or cheap) to manufacture on a large scale.
This is a cartoon summarizing the replication cycle of the coronavirus, and possible targets for drug therapy I just discussed in this thread.
So as summary, potential drug targets include:
1) Attachment inhibitors
2) Polymerase inhibitors
3) Replicase inhibitors
4) Protease inhibitors
5) Maturation inhibitors
1) Attachment inhibitors
2) Polymerase inhibitors
3) Replicase inhibitors
4) Protease inhibitors
5) Maturation inhibitors
