1)"The only measurement of a mutation rate in a β-coronavirus suggests that this site will accumulate ~10^–6 mutations in each round of replication. Each replication cycle takes ~10 hr, and so there are 10^3 cycles/year. "
2) but the argument that there are 1000 cycles of replication/year is *only* true if one considers 10^4 being ~8760, *and* only 1 viral mRNA replicates.
there are numerous other issues with this math.
3)if anyone thinks the math on estimating the chances of obtaining a furin cleavage site is simple... its not. the assumptions about the system, entropy of mrna, evolutionary fitness, parallel virion replications and mutations, host attacking virions cutting down #'s are critical
4) but the nice thing about this paper is it allows me to double down on my hypothesis of the impossibility of generating just 1 full codon at the s1/s2 junction in 1 replication.
in fact, for *any* codon to be inserted in 1 transcript, it would take
1.56e18 hours.
5) The universe is 1.38e10 years old or only
1.21e14 hours old.
so any model or algorithm that focuses only on 1 strand replicating won't recapitulate whole that site, ever.
take note, you'll need to factor how many virions are produced on average per cell/host infection...
6)the same by the numbers paper mentions 1mL sputum having 1e7 virions. ok. lets assume this is how much someone infectious has when finally clearing out the virus and it finishes replicating as its being fought off. ok? because it CANT replicate forever and we need some limits.
7) thats 2^23 (23 rounds of replication) if 1 round is 10 hours. so ~10 days. that lines up nicely. in 1 person(or bat, but given what @BillyBostickson and @KevinMccairn know about this virus killing the host through depriving them of olfaction, bats arent the natural host)...
8) in 10 days, we've had 2^23 pulls at this lever, which I've mentioned is ((1*10^-5)/5)^3 = 8e-18 chance to create 1 codon. (you divide by 5 not 4, since an event being 4x more common means there's a 1/5 chance LOL basic math)
then to finish the FCS, you need to repeat this 3x.
9) (8e-18)^3 = 5.12e-52
no. absolutely not happening. not in 1 host. not in humans, god no in bats that it would be killing if it were even from bats and replicating long enough to be transmissible and then kill them from lack of olfaction + detecting food.
check my math.
10/11) even if all the cells in my body were host to 1m virions each (3.4e13 * 1e6), thats only 3.4e19 pulls at one go. it cannot be enough to statistically account for the mathematical impossibility of generating a fully functional FCS.
11/11) in that example, google says a cell weighs 3.5e−9 g, and if 1 virion is 1fg, then 1e6 of them = 1e-9g. so nearly a third of all my cells would be virions by weight.
For example, SARS-CoV-2’s genome closely resembles that of a bat coronavirus, but a small section of the
genome called the “polybasic cleavage site,” believed to provide a selective advantage for disease transmission, would have been expected to evolve over time but instead
is present in the earliest sequences of the virus. Investigators can further determine whether the infecting agent’s genome so closely resembles a given reference
strain that a period of limited or no replication is likely. Such socalled “frozen evolution,” when an infecting
agent’s genome lacks the expected accumulation of mutations over time, suggests that alternate origin hypotheses such as a laboratory accident must be explored.