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ShaiberAlon / COVID19

A place to put COVID19 public resources
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COVID-19 literature #1

Open ShaiberAlon opened 4 years ago

ShaiberAlon commented 4 years ago

A place to dump relevant literature and possibly summaries too.

Tags in the format [tag_name] are added below each paper to allow for searching for specific topic.

ShaiberAlon commented 4 years ago

image https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1 [genomic variation][genome][genomic deletion]

A 382 nt deletion covering part of ORF-7 and most of ORF-8 results in attenuation of ORF-8 as well as downstream ORFs (protein N). Possibly leading to attenuation. A similar deletion was observed in the SARS epidemic.

They also mention that a common mutation in ORF8 partitions clades of SARS-COV-2. Here is a zoom-on on entropy of mutations on that ORF (from Nextstrain): image And how it partitions genomes: image

ShaiberAlon commented 4 years ago

image https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa036/5775463 [genomic variation][genome]

Sequenced genomes from 10 patients in Wuhan early in the epidemic.

One interesting thing: they say that there is evidence of an early (occurring in bat before the emergence of SARS-COV-2) of a recombination event in ORF 1b. According to their figure 4 (and text) the receptor binding domain of the spike protein spans area of amino acid positions ~343-536.

They show that despite the fact that SARS-COV and SARS-COV-2 belong to two different clusters according to full genome phylogeny, the spike protein sequence of SARS-COV-2 is more similar to that of SARS-COV than to that of more closely related coronaviruses from bats. Very interesting. This suggests (and since then has been shown to my understanding) that SARS-COV-2 binds to the same receptor (ACE2) as SARS-COV. The more distantly related MERS-COV binds to a different receptor (Cd26).

They also say:

Our results suggest that recombination events are complex and are more likely occurring in bat coronaviruses than in 2019-nCoV.

ShaiberAlon commented 4 years ago

image https://www.nature.com/articles/s41586-020-2196-x [general][epidemiology]

Studied 9 patients in Gernany. They successfully culture the virus from swab and sputum samples, but not from stool samples (regardless of viral RNA load in stool sample, which could be as high as in upper respiratory at times). They also could not culture the virus after day 8 (from onset of symptoms), "despite ongoing high viral load".

They also use ratio of sgRNA (subgenomic RNA) to genomic RNA to indicate presence of replication in throat and lack thereof in stool.

They detect the rise of a single nucleotide polymorphism (SNP) in the RNA sequenced from one patient which appears to have risen during infection. They confirm the SNP using RT-PCR and show that it has differential presence in swab and sputum samples, and say that this indicates that the virus is truly replicating in sputum and that it's presence there is not merely due to shedding from the lung. This mutation is G6446A. Interestingly, I don't see such a mutation at all on Nextstrain.

They show that peak viral load of SARS-COV-2 are much higher than that of SARS.

Very confusing: from their Figure 2 (and corresponding text): they say that in one patient it looks like the virus in independently replicating in the gut. But then, why are they not successful in culturing in from stool? is it replicating in upper GI, and then just dies on the way down? Is ACE2 known to express more highly in upper GI than lower GI? They discuss this a bit, but don't really address it. Their conclusion is that it definitely replicates in the GI.

They mention the presence of a poly-basic cleavage site in the spike protein in SARS-COV-2 that is absent from SARS-COV and say that this might allow SARS-COV-2 to infect throat cells efficiently despite low density of ACE2.