Avian Flu Talk is reporting pangolin as an intermediate host, while here we are following the ACE2-leucine trajectory for snake (post #314). One study links DPP4 (posted earlier in the thread linking Thai oseltamivir), to leucine:
Mar 2017 DPP4 / Leucine Aminopeptidase
Serum protease activity in chronic kidney disease patients: The GANI_MED renal cohort. - PubMed - NCBI
We note that the second hotspot for 2019-nCoV was position 494 (post #299), but also the leucine at position 455.
Another important link in the studies of post #314 is the mouse hepatitis virus strain A59 (previous posts) link:
WHV A59 / Proteosomal Inhibitor MG132
Severe acute respiratory syndrome coronavirus replication is severely impaired by MG132 due to proteasome-independent inhibition of M-calpain. - PubMed - NCBI
'....strongly inhibits SARS-CoV viral life cycle....bortezomib actually led to increased viral titers and pathology....Since MG132, a tripeptide aldehyde (benzyloxycarbonyl-leucyl-leucyl-leucinyl, or ZLLLa1, comprised an unparalleled capability of inhibiting SARS-CoV replication
, we hypothesized that inhibition of another proteolytic enzyme is responsible for inhibition of viral titer: m-calpain, a cysteine protease.'
When immediately searching for calpain links to snakes, we come up with both suspects for intermediate hosts (Bungarus and Naja) of 2019-nCoV. We'll link Naja first, because of the plant potyvirus link to papain (previous posts):
Snake / Calpain
snake calpain - PubMed - NCBI
Naja, Taiwan Cobra Inhibits Cysteine Protease
Purification and characterization of a new cystatin inhibitor from Taiwan cobra (Naja naja atra) venom. - PubMed - NCBI
'....S-carboxymethylpapain....inhibits cysteine proteases of the papain family....most closely related to the recently described human cystatin M which also has a similar five-residue insertion starting at position 76.'
This is an interesting clue to why mice and rats do not figure into the 2019-nCoV host hypothesis (previous posts):
Bungarus multicinctus / Apoptosis of Rat Neurons
Beta-bungarotoxin is a potent inducer of apoptosis in cultured rat neurons by receptor-mediated internalization. - PubMed - NCBI
We next link another Thai med used against 2019-nCoV, ritonavir, to calpain:
(2002) HIV Protease / m-Calpain
Ritonavir inhibition of calcium-activated neutral proteases. - PubMed - NCBI
'....Both human HIV protease and calpains share a similar secondary structure, where the active site is flanked by hydrophobic regions. Ritonavir, a hydrophobic HIV protease inhibitor, also inhibits calpain activity.'