Submission Details

Design Rationale:

Rationale: This tripeptide matches the three amino acids at the angiotensin I C-terminus. Pantoliano and coworkers speculated (in their 2004 publication on the crystallographic characterization of ACE2) that the conformational distortion induced in ACE2 by substrate binding (within the active site cleft) might be adequate to disfavor viral binding. They incidentally noted that ACE2 could operate on non-native substrates, and that catalytic efficiency processing angiotensin I was orders of magnitude less than that of angiotensin II, despite good binding. This may imply that simple peptides may function as quasi-inhibitors. To be clear, the goal here would be to induce the "protected conformation" of ACE2. This peptide is not intended to target viral proteins. (Fragment x0072 was arbitrarily selected just to be able to submit the form.) If true, then perhaps simple digestion of protein could supply meaning levels of suitable peptides. This would suggest that diet may be a contributing factor to people's vastly differing levels of susceptibility to COVID-19. Otherwise, other modes of delivery could be considered (IV, aerosol). Furthermore, it will be noted that the aliphatic component of chloroquine is similar to remdesivir, nitazoxanide, and a number of other small molecules believed to have in vitro efficacy against SARS-CoV-2. This structure may actually fit well within what Pantoliano and coworkers called the "Try510 lid" of ACE2. A summary document is provided here: https://pdfhost.io/v/YJCy0DEiO_covid19pdf.pdf (I apologize for the crudeness of Figure 2 therein, given the specialization/sophistication of those with whom I am currently sharing!)

Other Notes:

Also, along the same lines you may be interested in these simple molecules which can probably be obtained in two steps from thymidine and adenine, respectively: CC1=CN(C(NC1=O)=O)[C@H]2C[C@@H]([C@H](O2)CN(CC)CC)O, CCN(CC)CCCCNC1=NC=NC2=C1N=CN2

Inspired By: