[Tomassci (OP)]

We all know viruses work by entering the cell and then hijacking its machinery to make copies of itself. Now my question is, if it's possible for a virus to do all of this in vitro, basically replicating without a cell.

I was thinking of using a virus that doesn't utilise membranes to do the work, as well as putting it in the appropriate solution of the basic building blocks (+ enzymes). Could that work?

[evan_au]

if it's possible for a virus to (replicate) in vitro

"In vitro" means in glass, eg the ubiquitous Petri dish.

A lot of biological research (eg COVID, as a recent example) is done in vitro, because:
- In vitro research is cheap and quick
- It is unethical to infect a lot of people with COVID and then give them some untested medication, just to see if that medication has a chance of working. The initial promising results for Ivermectin were found using in vitro lab screening of known medicines.
Original paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129059/

(virus) replicating without a cell

Viruses are specifically tuned to enter a specific cell. For example, SARS-COV-2 interacts with two proteins found at the surface of a cell before it can enter the cell, triggering release of its RNA. Once inside the cell, it interacts with the ribosome to generate all the proteins to build new virus particles, and replicate the RNA too. This requires a steady supply of transfer RNA, loaded with amino acid building blocks. These are normal functions of every living cell, but they are beyond our abilities to reproduce outside a cell, without the cell's DNA carefully regulating thousands of genes and thousands of enzymes on a second-by-second basis.

In vitro does not mean that the virus is there by itself. You also put cells from a host organism, and watch how the virus infects and kills the living cells. Typically, these cells come from an immortalised cell line, so, provided with nutrients, it will keep multiplying.
- The original Ivermectin tests were performed with kidney cells from an African green monkey

One of these cell lines came from a woman who died of cervical cancer in 1951 (HeLa cells); others have come from an aborted baby in 1973 (HEK 293 cells). Some people object to the COVID vaccines (developed in 2020/2021), on the basis that the virus was tested using fetal tissue, and they object to the original abortion. But other cell lines are becoming available which are donated by consenting adults, so should raise fewer ethical concerns.

See: https://en.wikipedia.org/wiki/Immortalised_cell_line#Examples

if it's possible for a virus to do all of this in vitro

In vitro research is very valuable, as you can investigate many leads cheaply and quickly. But it has severe limitations, too.

For example, Ivermectin looked good in a dish - you can just drop Ivermectin into the cell culture and see what happens. But Ivermectin has so far shown itself useless against COVID in living organisms.
- The cellular concentration of Ivermectin used in the lab work was far higher than can be achieved in living organisms.
- As a large molecule, Ivermectin is not well absorbed by the gut, so it does not enter the bloodstream where the SARS-COV2 virus is busy infecting cells in every organ. But Ivermectin is great at killing intestinal parasites - which is what it is marketed for.

Vaccines can't be tested in vitro, either. Vaccines require the interaction of many types of immune cells, over a period of days to weeks. In vitro research usually has one or a few types of cell, and can't replicate the complexity of the immune system (at least, today).

[Bored chemist]

Ivermectin is not well absorbed by the gut,

It is absorbed well enough to be toxic.

One problem with in vitro testing is that you can use essentially any dose you like.
At a high enough dose Ivermectin may well inhibit SARS 19
But, at that dose, it is too toxic to humans to be useful as a treatment.