Tracking the relevant researches of CADD drug development against COVID-19


Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis. Converts angiotensin I to angiotensin 1-9, a nine-amino acid peptide with anti-hypertrophic effects in cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts as a beneficial vasodilator and anti-proliferation agent, counterbalancing the actions of the vasoconstrictor angiotensin II. Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin. Also cleaves other biological peptides, such as apelins (apelin-13, [Pyr1]apelin-13, apelin-17, apelin-36), casomorphins (beta-casomorphin-7, neocasomorphin) and dynorphin A with high efficiency. In addition, ACE2 C-terminus is homologous to collectrin and is responsible for the trafficking of the neutral amino acid transporter SL6A19 to the plasma membrane of gut epithelial cells via direct interaction, regulating its expression on the cell surface and its catalytic activity. [Uniprot]


Catalytic pocket

Receptor: 1R4L

Pocket Residues:

Chain A: S47 N49 Y50 N51 T52 L120 S124 Y127 S128 L144 E145 P146 N149 E150 M152 A153 L176 W203 D269 M270 W271 R273 F274 T276 M332 T334 D335 P336 A342 V343 C344 H345 P346 T347 A348 W349 D350 L359 M360 C361 T362 K363 V364 D367 D368 L370 T371 H374 E375 H378 D382 H401 E402 E406 S409 T445 T449 T453 R460 L503 F504 H505 V506 N508 D509 Y510 S511 F512 R514 Y515 R518

PPI surface (ACE2:S-glycoprotein)

Receptor: 6M0J

Pocket Residues:

Chain A: S19 T20 I21 E22 E23 Q24 K26 T27 F28 L29 D30 K31 F32 N33 H34 E35 E37 D38 L39 F40 Y41 Q42 L45 W48 N49 N61 K68 F72 Q76 L79 Y83 Q89 V93 Q96 M323 T324 Q325 G326 F327 W328 E329 N330 D350 G352 K353 G354 D355 F356 R357 I379 M383 A386 A387 Q388 P389 F390 R393