Antivirals

Viruses which have their genomic material made of DNA and are incorperated into the nucleus of host cells for transcription of said DNA into mRNA by host polymerases

Viruses which have their genomic material made of RNA and use their own enzymes to synthesize mRNA in the cytoplasm
Can be positive sense (which is what our normal mRNA is and can be directly used by ribosomes to make viral protein)
negative sense (which has to then have synthesis into positive sense mRNA)
Or both

It is a type of RNA virus which rather than being directly used by ribosomes to make proteins or used to make mRNA, it instead encodes for DNA, which is then incorperated into the host nucleus

nonenveloped viruses are more stable

+RNA viruses (can be directly used to produce viral proteins)
enveloped (less stable outside the host)

Infect upper respiratory tract only, about 15% of common colds?

Infect lower respiratory tract, high mortality, zoonotic

Viruses which jump from another animal to humans. Tend to be the source of more deadly viruses as viruses ideally don't want to kill their host, but animal viruses are not well attuned to infecting humans

A protein found on the membranes of human cells, mainly in the respiratory tract

They are covered in spike proteins, which bind to ACE2 on vulnerable (permissive) cells, and allows them to enter the cell (vaccines make these spike proteins so that antibodies know to target them when coronavirus enters the body)
These spike proteins mutate often which is why there is vaccine resistance and new variants of COVID

Virus attaches to target cell

Virus penetrates into cell

Viral genomic material is unleashed into the cell

Production of viral mRNA from viral genome (not needed for +RNA viruses as they come ready to translate)

Synthesis of viral proteins and nucleic acids from viral mRNA

Creation of a new capsid and virus using the viral proteins made by the cell

Buddy from the cell membrane (in enveloped viruses) or rupture of the cell (in nonenveloped viruses) to release newly formed viruses and allow further infection

Hemagglutinin (HA)
M2
Neuraminidase (NA)

Binds to terminal sialic acids on target cells which triggers endocytosis of the virus

Activates once in the low pH environment of the endosome. This lets acid into the virus and triggers the release of the viral ribonucleoprotein (RPN)

After replication, it cleaves sialic acids from the cell receptors and allows release of influenza to non infected cells

Zoonotic strains of influenza, H1N1, H2N2, H3N2, etc. These classifications are named for the different variations of hemagglutinin and neuraminidase on the virus

Mostly exclusive to humans, slower mutation with less diversity

Humans and dogs, less common

Pigs and cattle, little human transmission

Not super clear, but seem to interfere with M2, preventing uncoating of influenza to stop release of viral components into the cell

amantadine
rimantadine
memantine

amantadine

M2 alterations, high levels of resistance

They mimic the intermediate of the reaction neuraminidase (NA) performs to cleave sialic acids from the host membrane. This causes them to bind to NA and prevent them from completing the cleave, leaving the newly made influenza stuck in the membrane of the host cell. Effective in influenza A and B

zanamivir
oseltamivir

a transition state inhibitor (zanamivir)

Have to take very early in the course of the disease
high resistance through conformation changes of NA

-RNA viruses, use RNA-dependent RNA polymerase to make +RNA (mRNA) from the -RNA which can then be used by ribosomes in the cell to make viral proteins

In order for a ribosome to read mRNA and produce proteins from it, it requires a specific 5'-cap which is difficult for viruses to make. Different viruses have different methods to cap their mRNA so that our cells will make proteins with them.

It steals the 5'-cap from mRNA that is in the cell already using an endonuclease and attaches it to the mRNA that it is producing

Inhibits the endonucleases of influenza to prevent them from stealing 5'-caps from host mRNA

baloxavir marboxil

High potency, only taken with a single dose
Frequent resistance

Drugs that look like nucleosides, but when they are incorperated into the RNA or DNA chain will cause some type of issue. Chain terminators prevent the addition of more nucleosides, mutagenetic nucleosides cause rapid mutations that make the virus unstable

It is a prodrug which is only activated by viral thymidine kinase, after which it is incorperated into the viral DNA and prevent additon of the next nucleoside in the chain. Very little side effect because without the viral thymidine kinase it will not be activates and won't be incorperated into human RNA or DNA. Used against HSV

Aciclovir

Loss of the viral thymidine kinase which activates it, not very common

Valaciclovir
Penciclovir
Ganciclovir

Doesn't cause chain termination like aciclovir and valaciclovir, instead caused mutations. Also doesn't require activation by viral thymidine kinase

It is used by and inhibits DNA polymerase and causes rapid mutations or inhibition, used for herpes. Nucleoside antimetabolites

Doesn't require activation like aciclovir because it has an analog of the first phosphate group which allows human cells to finish activation. Gets around aciclovir resistance but much more toxic.

Cidofovir

Incorperated into viral RNA, and allows pairing with both cytidine and uridine depending on configuration. Eventually leads to lethal mutagenesis

Fairly broad spectrum against RNA viruses

Ribavirin

They inhibit proteases which hepatitis C uses to process their proteins

boceprevir
telaprevir

They inhibit NS5A in hepatis C. It is unknown what NS5A does, but it's inhibition leads to cell death

Ombitasvir
Daclatasvir
Ledipasvir

Inhibitors of the RNA dependent RNA polymerase found in hepatitis B viruses, used together with NS5A inhibitors as the mainstay of anti hepatits C therapy

Dasabuvir
Sofosbuvir

Combination of ledipasvir and sofosbuvir, curative for hepatitis C

It contains a proofreading exonuclease that detects the error and cuts it out

Remdesivir
Molnupiravir

C3-like protease in COVID which prevents processing of COVID proteins

Retrovirus

It acts as an RNA dependent DNA polymerase that makes DNA from the RNA strand
Then it acts as an RNase that breaks down the RNA strand
Then it acts as a DNA dependent DNA polymerase to make a new strand from the now single DNA strand

They inhibit reverse transcriptase by binding to an allosteric site and preventing its function

Nevirapine
Efavirenz
Etravirine