Was SARS-CoV-2 (COVID-19) artificially created as a weapon?

There's a lot of people spreading a conspiracy theory that SARS-CoV-2 was artificially created as a weapon:

TL;DR: Nonsense

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You've probably seen pictures or models of the SARS-CoV-2 virus, with its now iconic "spikes" that stick out from the surface. You've probably also heard something about SARS-CoV-2 "binding" to the "ACE2 receptor". What does all that mean?

Some very quick (and tremendously oversimplified) background: (For biochem folks reading this, I'm really simplifying this, leaving out things like "start codons", "stop codons", "open reading frames", etc, on purpose)

A gene can be thought of as a long series of nucleotides (the famous A, T, G, and C). Taken 3 at a time, those nucleotides are called "codons", and each codon is the blueprint for one of 20 amino acids. The encoding scheme is redundant: each amino acid has more than 1 three letter code (a codon) that codes for it. As the biochemical machinery of the cell works its magic, each codon serves as a blueprint for an amino acid, and long strings of these amino acids (folded and knotted up in complex ways) are called a "protein".

When you hear biologists talk about "mutations", the thing being mutated is one of those nucleotides: an A might become a G, or a C might become a T or an A. (Much much larger mutations are possible, but aren't germane to this discussion) Because those "mutated" nucleotides are part of a blueprint, the protein that eventually gets expressed is very slightly different than that protein would have been had it been expressed via the un-mutated blueprint.

For the record, when the mutation consists of a single nucleotide being changed, we call it a SNP: "Single Nucleotide Polymorphism"

Another word I want to introduce is "residues". In this context, the word serves as a shorthand for "amino acid residues." When amino-acids get assembled into a protein, the bits of the molecule that make it an acid (called a "carboxyl group") get chopped off, so we call the remaining bits of the amino acid that actually form the protein an "amino acid residue" or just "residue". It's perfectly fine if that's confusing, just know that when you see the word "residue" in this context, you should think "oh, that's an amino acid"

Are we all together on the relationship between nucleotides, codons, amino acids, and genes, and that the gene serves as a blueprint for a protein? Good, off we go.

When a virus attacks a cell, it does so by binding itself to a "receptor". In the case of SARS-CoV-2, the molecules that do that binding are proteins at the tip of those now famous spikes. The molecules of the cell that are "bound to" are proteins called "receptors". For future reference, when we talk about "antibodies", we are talking about proteins created by your immune system that can recognise and destroy those proteins at the end of the spike.

I need to pause here and note that generically, any small molecule that binds to a much larger one (like say, a protein of a virus binding to a receptor in the cell wall) is referred to as a "ligand".

The traditional model of the way a ligand fits into a receptor is "the way a key fits into a lock". It's a little more complicated than that because unlike physical locks and keys, receptors have a little bit more leeway in deciding what constitutes "fits". A ligand that is "close enough" to the correct ligand (differing by, say, a handful of SNPs in the blueprint) can still fit in that receptor "lock", though not as efficiently. (If you were reading a molecular biology textbook right now, it would be using the word "affinity" to describe how likely the particular ligand is to be able to fit into that particular receptor.)

Within a given ligand, the specific amino acid residues that make up the "docking mechanism" between the ligand and the receptor have the fancy name "receptor binding domain". I will be using the acronym RBD because I am a lazy typist.

Now, with that background, here are some hints that tell us that it's incredibly unlikely that SARS-CoV-2 was created as a weapon and is instead the product of evolution.

1. In coronaviruses, the RBD of the spike protein is the region that contains the most variation between viruses in that family. (That is, when a member of the coronavirus family mutates into a new species, that mutation always involves SNPs in the RBD of the spike protein). There are a half dozen residues in the RBD that serve as the important "binding agents" to the ACE2 receptor. As one would expect from our experience with the rest of the coronavirus family, five of those six residues in SARS-CoV-2 have mutated from their SARS-CoV progenitors. The important thing to note is that with these five mutations, the binding affinity of the SARS-CoV-2 RBD is lower than for SARS-CoV. No one setting out to design a biological weapon would have created an RBD that was less likely to result in an infection that the original form that the virus had. It's also noteworthy that outside the RBD, the spike protein in SARS-CoV-2 is very very similar (evolutionary biologists would use the phrase "highly conserved") to the spike protein in SARS-CoV... an indicator that the handful of changes in the RBD are the product of evolution, not design.

2. Backing up up from the protein, and examining the virus's RNA for a moment: remember a few paragraphs up when we talked about a gene being made up of nucleotides? Those nucleotides are attached to a phosphate backbone. Think of gems hanging from a string necklace, where the nucleotides are the gems, and the the "phosphate backbone" is the string holding them together.
   In modern artificial genomics, there are a handful of phosphate backbones that are used in the creation of synthetic viruses. These are stable, well characterized, and straight-forward to use. Wanna know which one of these SARS-CoV-2 uses as a phosphate RNA backbone? None of them. Instead, the SARS-CoV-2 phosphate backbone is virtually identical to that of SARS-CoV, another indicator that this is the product of evolution and not manufactured.

3. "Phylogenetic tree" is a fancy way to say "the evolutionary history of a genome". The phylogenetics of viruses is well outside of my expertise, but when I read papers of experts discussing the phylogenetics of SARS-CoV-2, the big debate seems to be whether SARS-CoV-2 is a descendant of SARS-CoV, or whether they are both the result of common descent from an older ancestor. No paper I've seen thus far seems to even hint at any other phylogenetic origin.

I'm sorry this presentation didn't have a slick video with fancy graphics and some talking head shouting "well, IT'S OBVIOUS!"

It's not obvious. You have to look at the molecular biology... and now you can.

I'll leave off with a brief mention of the hypothesis floating around that SARS-CoV-2 may not have been man-made, but it could have been collected in the wild, stored in a lab somewhere, and accidentally escaped from the lab.

I don't have any particular opinion on that, and I don't see anything in the biology that rules it out. The biology lesson in this post is only to persuade you that it's incredibly unlikely that SARS-CoV-2 was designed by a human being.

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