I am preparing a 16,000 or so word analysis covering the outbreak and comparing several viral proteins of SARS and nCoV2019, in monograph form, to be published on Amazon Kindle within a few days.
I would note here two new findings.
nCoV2019 has a furin-sensitive motif at the traditional S1/S2 border fo the spike protein, i.e. RRAR, that was lacking in SARS (which depends on cathepsin cleavage a few amino acids downstream). nCoV2019 lacks the secondary minimal furin cleavage site, i.e. RNTR, that is found in SARS. Therefore, the endoproteolytic cleavage pattern is expected to be different between nCoV2019 and SARS.
Prediction of O-glycosylation sites reveals a cluster of Serine residues, just before and after the RRAR cleavage site, with a high propensity to form a “mini-mucin” patch at that site. It is positioned to protect the putative fusion peptide region in the native or pre-fusion Swiss-Model projection of the probable nCoV2019 structure.
I highly recommend the article posted on Amazon Kindle by Bill Gallaher. It is written for a lay audience, but packed with important information.
Most pertinent to the new outbreak:
nCoV has an insertion that adds a furin cleavage site - RRXR - at the boundary of S1and S2 in the spike precursor.
This is the same type of mutation that changes H5 influenza virus and other avian viruses into more pathogenic variants
Bottom line is a new furin site upstream of the fusion peptide in the HA makes H5 etc more fusogenic in more tissues.
Likely similar story in nCoV.
This furin site is not present in SARS-CoV or other bat viruses closely related to nCoV.
More complex in 1918 flu - a different mutation in a different protein - but enhanced cleavage also contributed to enhanced spread as well.
This novel insertion in nCoV adds a minipatch of o-linked glycans in the prefusion trimer. These glycans overlay the fusion peptide in the adjacent monomer of the trimer. The fusion peptide is likely to be a major neutralization epitope so this newly added minimucin patch probably makes a difference in virulence and at least perhaps will make it more challenging to develop a vaccine.
Both the new furin site and the o-linked glycans are unique features of nCoV and important. Haven’t see this picked up yet by anyone else.
Both Bob Garry and I have mentioned the monograph my son and I are in the process of publishing on Amazon Kindle, bu this was never about selling books. The following is a pdf file of the book, that may be downloaded, shared, copied or printed for FREE. Just not to be republished in any part without permission of the authors.
An updated and corrected version of the monograph is posted here again for FREE. As for the original version, the following is a pdf file of the book, that may be downloaded, shared, copied or printed for FREE. Just not to be republished in any part without permission of the authors.