- Genomic analyses of the new coronavirus have revealed that its spike protein differs from those of close relatives, and suggest that the protein has a site on it which is activated by a host-cell enzyme called furin.
Someday I hope to see an objective analysis of covid-19, and get some confidence around whether this was naturally-occurring or a mistake. Labs do work on these viruses and stupid things do happen in high-risk institutional environments. At this point in time, it doesn't matter, and won't make things better. But even if the chance that this was due to a mistake is small, if it was a mistake, then things can and need to be changed.
Ever read The Hot Zone, mk? When we first discovered Ebola we thought it was Marburg. Why? Because we'd seen Marburg from monkeys at an animal testing facility in Germany. Then it showed up in Africa in a few different places. then it showed up in the Ebola Valley but oh holy fuck it was substantially nastier than Marburg but still a filovirus. So everybody knows Ebola, not Marburg, except the bioweapons community because Marburg is the strain that everybody's cabinet of curiosities started to fuck with because stocks were unconstrained prior to 1972. So weaponized it was. Using your logic, Ebola is obviously deliberately weaponized Marburg. Except it's not. It jumps from monkeys on the reg. It's been sequenced jumping from animal hosts on the reg. Viruses mutate. Bacteria mutates. SARS was bad enough but viruses mutate. Ebola and Marburg are both filoviruses but Ebola did not come from Marburg, despite well-documented efforts by numerous bioweapons labs to do just that. That's Bill Gates five years ago.
You've got me wrong. I'm not talking about weaponization. Labs are actively creating these very types of mutations out of scientific curiosity. Sometimes it's by forced mutation: https://www.sciencedirect.com/science/article/pii/S0042682212004187 Sometimes it's by direct engineering: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738192/ https://www.ncbi.nlm.nih.gov/pubmed/26545254 https://www.ncbi.nlm.nih.gov/pubmed/30310104 Scientists are taking these very viruses and mutating them to better understand their functions, including cross-species infection. I am simply wondering if someone goofed when doing something we know is being done.To study the mechanisms underlying the host cell specificity and susceptibility to coronavirus and coronavirus–host interactions, the Beaudette strain of IBV was adapted from chicken embryo to a monkey kidney cell line, Vero, by continuous propagation for 65 passages (Shen et al., 2003, Shen et al., 2004).
Site-directed mutagenesis studies revealed that the S1/S2 cleavage by furin was not necessary for, but could promote, syncytium formation by and infectivity of IBV in Vero cells. In contrast, the second site is involved in the furin dependence of viral entry and syncytium formation. Mutations of the second site from furin-cleavable RRRR/S to non-furin-cleavable PRRRS and AAARS, respectively, abrogated the furin dependence of IBV entry.
Using a molecular cDNA infectious clone to generate a corresponding recombinant virus, we show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein. While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS.
Here we engineered full, partially deleted (-29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor.
I appreciate the clarification, but I also know that generally the people who work with pathogens practice better epidemiological controls than the people who buy bush meat. My mother did epidemiology. She knew a few cases of accidental exposure to nasty shit - one of her coworkers actually injected himself with anthrax and another exposed himself to rabies. But at the same time, my sister spent two weeks in the ICU with hantavirus and I lost a classmate to plague. Yeah crud leaps out of petri dishes sometimes but there's an ocean of the stuff out there just past where the streetlights cease to shine.
I have less faith. I've seen scientists do things that no one with an advanced degree in science would be expected to do. Things with radioactive material, body fluids, cultures. Everyone has stories. Lab casual. It's a thing. Sometimes the worse offenders are those that have been in the lab the longest.
I’m also hesitant to believe that this is anything other than a random mutation (like you say) and subsequent human exposure. But I’m also not as far into virology as mk, for sure. I don’t think mk means to imply that covid was intentionally weaponized, merely that it may be the result of careless laboratory tests gone wrong. Of course, it’s certainly possible, but the pangolin meat market story doesn’t seem too far-fetched to me. But yeah. I’ll gladly research and discuss that with you sorry saps over the coming months, Hubski. Thanks.
Jared Diamond pointed out in Guns, Germs & Steel that one of the dominant factors in the colonization of the world by Northern Europe was the fact that Northern Europeans had, for hundreds of generations, spent the entire winter cooped up with their livestock. Chicken Pox, Cowpox, flu, rabies, glanders, anthrax, chlamydia, toxoplasmosis, Q fever, all have a traced zoonotic origin and Northern Europeans had developed immunity that North Americans, Asians and Africans lacked. Likewise, a lack of immunity to malaria substantially curbed Northern European expansion into Africa even after epidemics had swept through. Bugs come from critters. Critters shed bugs. Sunrise, sunset. The amount of germs in the lab is overwhelmingly swamped by the amount of germs in nature. Not only that people don't really think of evolution in microorganisms the same way they think about it elsewhere. I mean, it took what? 50 years for pigeons to turn black? 500 years for crabs to grow faces? Fruit fly generations happen every two weeks - in a year you can get the same genetic deviation in a fruit fly that you can get from humans in 500 years. Viruses mutate like a mutherfucker and their generation time is in the "hours" range - R0 measures spread in humans, not viral lifecycle time. I can't find a number for SARS or NCOV but HIV is like 6 hours and HIV is considered an exquisitely sensitive and slow-growing virus.
The way “Spike” is used in virology breathes new life into Boris’s hacking scenes in GoldenEye, for me.