Antiviral drugs
Few drugs act against viruses, because a virus uses the host cell's own functions and a drug that poisons the virus poisons the host. A usable antiviral targets a mechanism specific to the virus, at a step of the viral life cycle from entry into the cell through uncoating, translation and protein processing to replication of the genome.
Why few antiviral drugs exist
There is a paradox in antiviral pharmacology: more is known about viruses than about any other type of parasite, and yet very few drugs are available. The reason is that viruses use many of the host's functions, so poisoning the virus means poisoning the host. Antibiotics do not work against viruses, because they are designed to act on the bacterial ribosome or the bacterial cell wall and a virus has neither. A drug therefore has to target mechanisms specific to the virus.
Drug targets along the coronavirus life cycle
In May 2020, some of the most promising pharmacological developments that might help patients already ill with COVID-19 acted at successive steps of the coronavirus life cycle.
Monoclonal antibodies, or convalescent plasma from patients who have been ill and so produced antibodies, could supply antibodies that block the virus's S protein from interacting with its receptor, but they need a large quantity of material. A serine protease is also important for viral entry, and it can be inhibited with camostat mesylate, a general serine protease inhibitor, whose clinical trial was due to complete in May 2020.
Once the virus is inside the cell it sits in a vesicle called the endosome, whose pH normally has to be relatively low to allow the virus to uncoat and disassemble. The idea behind chloroquine is that it inhibits this process, keeping the pH too high so that the virus is trapped in the endosome. As of May 2020 there was no evidence that chloroquine did anything good or anything bad against the coronavirus, and it was used for other purposes.
A coronavirus genome is translated first into two large non-functional polyproteins; a viral protease is then activated and cleaves them at particular residues, producing the 27 or so functional proteins that are important for the viral life cycle. A drug combination considered promising in May 2020 interferes with this protease; it has also been used to treat HIV, which uses a similar protease in its life cycle.
Remdesivir inhibits the virus's RNA-dependent RNA polymerase, without which the virus cannot replicate. In May 2020 it was considered the most promising of these candidates, on the basis of a recent clinical trial across Europe. In that trial it was well tolerated, and patients recovered in 11 days on average against 15 days in the controls, a 30% improvement described as consistent and promising for the future.
Ribosomal frameshifting as a drug target
In May 2020, some steps of the viral life cycle were not being investigated as drug targets, and one of them, ribosomal frameshifting at the translation step, had no clinical studies in sight. Ribosomal frameshifting is a process by which viruses can control their gene expression. Normally a ribosome binds a message, translates it from the start codon to the stop codon, and produces one protein. Some viral messages carry a programmed minus-one ribosomal frameshift signal, a strong secondary structure that blocks the ribosome's progress. The ribosome can fall off there, which is functionally equivalent to a stop codon, and one viral protein is produced. In some cases the ribosome instead goes back by one nucleotide, dissolves the secondary structure and continues translating, making a bigger protein that is entirely different from the one made without frameshifting. A virus can therefore produce two different proteins from a single message, a strategy of genome condensation.
The genome of SARS-CoV, a coronavirus, carries such a frameshift signal. The signal can be targeted pharmacologically, for instance with microRNAs or small-molecule inhibitors that interact with it and break the virus's frameshifting rates. A virus without the right frameshifting rates has an imbalance of proteins, such as of structural to enzymatic proteins, and cannot develop a mature viral particle.