Incidentally, also strong evidence against it being a lab-strain. It’s a wild strain.
Closest related viruses: bats and Malayan pangolins
Mutation Descriptions
Polybasic Cleavage Sites (PCS): They seem to have something to do with increased rates of cell-cell fusion (increased rate of virus-induced XL multi-nucleated cells). Mutations generating PCS have been seen in Influenza strains to increase their pathogenicity, and they had similar effects in a few other viruses. So it’s not exactly increasing virus-cell fusion, it’s actually… increasing the rate at which infected cells glom into nearby cells. Fused cells are called syncytia.
O-linked glycans : Are theorized (with uncertainty) to help the virions masquerade as mucin, so hiding from the immune system. (Mutation unlikely to evolve in a lab on a petri dish)
Arguments strongly in favor of it being a wild strain
It’s not that similar to one of the known lab-strains, so it probably was wild
The “polybasic cleavage site” and “O-linked glycans” mutations would have required a very human-like ACE-protein binding site, so basically only human or ferret cells
O-linked glycans are usually evolved as an immune defense, which isn’t something cell cultures do.
(Just following the recommendation to move this out of shortform so it can be tagged later.)
Chinese virology researcher released something claiming it SARS-2 might even be genetically-manipulated after all? ZC45 and/or ZXC21 backbone. Claims that the RaTG13 genome was a concocted cover-up. After assessing, I’m not really convinced of the GMO claims, but the RaTG13 story seems to have something weird going on.
EDIT: After assessing, I’m not finding the GMO claims convincing. The RaTG13 story does seem to have something weird going on, and there’s several people and papers that note weird inconsistencies (See the further thoughts, I don’t have a simple explanation.).
Additional little bit that reminded me of that cell-cell fusion trait… another paper described the SARS-CoV-2 autopsy results, and included this:
Multinucleated syncytial cells with atypical enlarged pneumocytes showed viral cytopathic-like changes, without obvious intranuclear or intracytoplasmic viral inclusions.
Translation: The paper-thin, high-surface-area (for gas exchange) cells wrapping your lung balloons (the pneumocytes in your alveoli) fuse together with each other into an ineffectual, clumpy mess with a way lower surface-area-to-volume ratio. These are fragile cells to begin with; they don’t even replicate themselves (other cells have to replace them when they break). They don’t seem to be producing virus themselves, but they do seem to be getting badly screwed up by things the virus is doing.
It was not genetically modified for use as a bioweapon
The mutations don’t resemble other well-known and well-characterized pathogenicity mutations too closely, in sequence or location
It probably wasn’t cultured as cell-culture in a lab-setting for an extended period
The virus was not notable to science prior to this event
Or in other words, it doesn’t look planned. Its most recent mutations look much more like a “natural variation let it jump species” sort of situation.
This doesn’t address situations like, for example, “dead bats with a wild-type virus being left near a bunch of ferrets or pangolins,” or something to that effect.
(ETA: Or… accidental release like this is still possible.)
Despite the virus being characterized in pangolins, after looking into this, I now think it is basically incorrect to think of this as primarily a “pangolin virus.” The pangolins were a dying canary in a coal mine, and probably caught it from something else that serves as the real reservoir species for this nCOV precursor*.
Paper on some of nCOV’s mutations
Incidentally, also strong evidence against it being a lab-strain. It’s a wild strain.
Closest related viruses: bats and Malayan pangolins
Mutation Descriptions
Polybasic Cleavage Sites (PCS): They seem to have something to do with increased rates of cell-cell fusion (increased rate of virus-induced XL multi-nucleated cells). Mutations generating PCS have been seen in Influenza strains to increase their pathogenicity, and they had similar effects in a few other viruses. So it’s not exactly increasing virus-cell fusion, it’s actually… increasing the rate at which infected cells glom into nearby cells. Fused cells are called syncytia.
O-linked glycans : Are theorized (with uncertainty) to help the virions masquerade as mucin, so hiding from the immune system. (Mutation unlikely to evolve in a lab on a petri dish)
Arguments strongly in favor of it being a wild strain
It’s not that similar to one of the known lab-strains, so it probably was wild
The “polybasic cleavage site” and “O-linked glycans” mutations would have required a very human-like ACE-protein binding site, so basically only human or ferret cells
O-linked glycans are usually evolved as an immune defense, which isn’t something cell cultures do.
(Just following the recommendation to move this out of shortform so it can be tagged later.)
Chinese virology researcher released something claiming it SARS-2 might even be genetically-manipulated after all? ZC45 and/or ZXC21 backbone. Claims that the RaTG13 genome was a concocted cover-up. After assessing, I’m not really convinced of the GMO claims, but the RaTG13 story seems to have something weird going on.
https://zenodo.org/record/4028830#.X2EJo5NKj0v
See here for my further thoughts on this.
EDIT: After assessing, I’m not finding the GMO claims convincing. The RaTG13 story does seem to have something weird going on, and there’s several people and papers that note weird inconsistencies (See the further thoughts, I don’t have a simple explanation.).
Additional little bit that reminded me of that cell-cell fusion trait… another paper described the SARS-CoV-2 autopsy results, and included this:
Translation: The paper-thin, high-surface-area (for gas exchange) cells wrapping your lung balloons (the pneumocytes in your alveoli) fuse together with each other into an ineffectual, clumpy mess with a way lower surface-area-to-volume ratio. These are fragile cells to begin with; they don’t even replicate themselves (other cells have to replace them when they break). They don’t seem to be producing virus themselves, but they do seem to be getting badly screwed up by things the virus is doing.
What exactly does “lab-strain” mean here? Does it means a strain with a already published sequence?
More specifically:
It was not genetically modified for use as a bioweapon
The mutations don’t resemble other well-known and well-characterized pathogenicity mutations too closely, in sequence or location
It probably wasn’t cultured as cell-culture in a lab-setting for an extended period
The virus was not notable to science prior to this event
Or in other words, it doesn’t look planned. Its most recent mutations look much more like a “natural variation let it jump species” sort of situation.
This doesn’t address situations like, for example, “dead bats with a wild-type virus being left near a bunch of ferrets or pangolins,” or something to that effect.
(ETA: Or… accidental release like this is still possible.)
Despite the virus being characterized in pangolins, after looking into this, I now think it is basically incorrect to think of this as primarily a “pangolin virus.” The pangolins were a dying canary in a coal mine, and probably caught it from something else that serves as the real reservoir species for this nCOV precursor*.
See: further explanation here