Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural viricides are produced by some plants such as eucalyptus and Australian tea trees.
The rhinovirus is the most common viral infectious agent in humans and is the predominant cause of the common cold. Rhinovirus infection proliferates in temperatures of 33–35 °C (91–95 °F), the temperatures found in the nose. Rhinoviruses belong to the genus Enterovirus in the family Picornaviridae.
In chemistry, an ionophore is a chemical species that reversibly binds ions. Many ionophores are lipid-soluble entities that transport ions across the cell membrane. Ionophores catalyze ion transport across hydrophobic membranes, such as liquid polymeric membranes or lipid bilayers found in the living cells or synthetic vesicles (liposomes). Structurally, an ionophore contains a hydrophilic center and a hydrophobic portion that interacts with the membrane.
Pleconaril (Picovir) is an antiviral drug that was being developed by Schering-Plough for prevention of asthma exacerbations and common cold symptoms in patients exposed to picornavirus respiratory infections. Pleconaril, administered either orally or intranasally, is active against viruses in the Picornaviridae family, including Enterovirus and Rhinovirus. It has shown useful activity against the dangerous enterovirus D68.
The maturation inhibitors are a class of antiviral drugs for the treatment of infection with HIV. They act by interfering with the maturation of the virus. Specifically, drugs in this class disrupt the final step in the processing of the HIV-1 gag protein, the cleavage of its immediate precursor by the enzyme HIV-1 protease. Unlike the class of drugs known as protease inhibitors, maturation inhibitors bind the gag protein, not the protease. This leads to the formation of noninfectious, immature virus particles, incapable of infecting other cells. No other class of drugs shares this mechanism of action, thus maturation inhibitors retain inhibitory activity against HIV infections with resistance.
Picornain 3C is a protease found in picornaviruses, which cleaves peptide bonds of non-terminal sequences. Picornain 3C’s endopeptidase activity is primarily responsible for the catalytic process of selectively cleaving Gln-Gly bonds in the polyprotein of poliovirus and with substitution of Glu for Gln, and Ser or Thr for Gly in other picornaviruses. Picornain 3C are cysteine proteases related by amino acid sequence to trypsin-like serine proteases. Picornain 3C is encoded by enteroviruses, rhinoviruses, aphtoviruses and cardioviruses. These genera of picoviruses cause a wide range of infections in humans and mammals.
The 3C-like protease (3CLpro) or main protease (Mpro), formally known as C30 endopeptidase or 3-chymotrypsin-like protease, is the main protease found in coronaviruses. It cleaves the coronavirus polyprotein at eleven conserved sites. It is a cysteine protease and a member of the PA clan of proteases. It has a cysteine-histidine catalytic dyad at its active site and cleaves a Gln–(Ser/Ala/Gly) peptide bond.
Scytovirin is a 95-amino acid antiviral protein isolated from the cyanobacteria Scytonema varium. It has been cultured in E. coli and its structure investigated in detail. Scytovirin is thought to be produced by the bacteria to protect itself from viruses that might otherwise attack it, but as it has broad-spectrum antiviral activity against a range of enveloped viruses, scytovirin has also been found to be useful against a range of major human pathogens, most notably HIV / AIDS but also including SARS coronavirus and filoviruses such as Ebola virus and Marburg virus. While some lectins such as cyanovirin and Urtica dioica agglutinin are thought likely to be too allergenic to be used internally in humans, studies so far on scytovirin and griffithsin have not shown a similar level of immunogenicity. Scytovirin and griffithsin are currently being investigated as potential microbicides for topical use.
MK-608 is an antiviral drug, an adenosine analog. It was originally developed by Merck & Co. as a treatment for hepatitis C, but despite promising results in animal studies, it was ultimately unsuccessful in clinical trials. Subsequently it has been widely used in antiviral research and has shown activity against a range of viruses, including Dengue fever, tick-borne encephalitis virus, poliovirus, and most recently Zika virus, in both in vitro and animal models. Since it has already failed in human clinical trials previously, it is unlikely MK-608 itself will be developed as an antiviral medication, but the continuing lack of treatment options for these emerging viral diseases means that much research continues using MK-608 and related antiviral drugs.
Danoprevir (INN) is an orally available 15-membered macrocyclic peptidomimetic inhibitor of NS3/4A HCV protease. It contains acylsulfonamide, fluoroisoindole and tert-butyl carbamate moieties. Danoprevir is a clinical candidate based on its favorable potency profile against multiple HCV genotypes 1–6 and key mutants (GT1b, IC50 = 0.2–0.4 nM; replicon GT1b, EC50 = 1.6 nM). Danoprevir has been evaluated in an open-label, single arm clinical trial in combination with ritonavir for treating COVID-19 and favourably compared to lopinavir/ritonavir in a second trial.
Pibrentasvir is an NS5A inhibitor antiviral agent. In the United States and Europe, it is approved for use with glecaprevir as the combination drug glecaprevir/pibrentasvir for the treatment of hepatitis C. It is sold by Abbvie.
GS-6620 is an antiviral drug which is a nucleotide analogue. It was developed for the treatment of Hepatitis C but while it showed potent antiviral effects in early testing, it could not be successfully formulated into an oral dosage form due to low and variable absorption in the intestines which made blood levels unpredictable. It has however continued to be researched as a potential treatment for other viral diseases such as Ebola virus disease.
EICAR is a drug which acts as an inhibitor of the enzyme IMP dehydrogenase. It is a nucleoside derivative which has both anti-cancer and antiviral effects, and was originally developed for the treatment of leukemia, but was unsuccessful in human clinical trials. It has broad spectrum antiviral effects with activity against pox viruses, Semliki forest virus, Junin virus, reovirus, influenza, measles virus and respiratory syncytial virus among others, although it is not active against coronaviridae such as SARS-CoV-1. This useful spectrum of activity means that EICAR and related derivatives continue to be investigated for the treatment of viral diseases.
3CLpro-1 is an antiviral drug related to rupintrivir which acts as a 3CL protease inhibitor and was originally developed for the treatment of human enterovirus 71. It is one of the most potent of a large series of compounds developed as inhibitors of the viral enzyme 3CL protease, with an in vitroIC50 of 200 nM. It also shows activity against coronavirus diseases such as SARS and MERS, and is under investigation as a potential treatment agent for the viral disease COVID-19.
GC376 is a broad-spectrum antiviral medication under development by the biopharmaceutical company Anivive Lifesciences for therapeutic uses in humans and animals. Anivive licensed the exclusive worldwide patent rights to GC376 from Kansas State University. As of 2020, GC376 is being investigated as treatment for COVID-19. GC376 shows activity against many human and animal viruses including coronavirus and norovirus; the most extensive research has been multiple in vivo studies in cats treating a coronavirus which causes deadly feline infectious peritonitis. Other research supports use in porcine epidemic diarrhea virus.
Valopicitabine (NM-283) is an antiviral drug which was developed as a treatment for hepatitis C, though only progressed as far as Phase III clinical trials. It acts as a RNA-dependent RNA polymerase inhibitor. It is a prodrug which is converted inside the body to the active form, 2'-C-methylcytidine triphosphate.
TMC-310911 is an antiviral drug which was originally researched as a treatment for HIV/AIDS. It is a protease inhibitor related to darunavir. While TMC-310911 was not ultimately developed as a medication for the treatment of AIDS, research has continued into potential applications in the treatment of other viral diseases, and in March 2020 it was entered into clinical trials for the treatment of COVID-19.
CMX521 is an antiviral drug discovered by Chimerix, which was developed for the treatment of norovirus, though it also shows efficacy against related viral diarrheas such as rotovirus and some sapoviruses, astroviruses and adenoviruses. It is a nucleoside analogue which acts as an inhibitor of viral RNA-dependant RNA polymerase.
Nirmatrelvir is an antiviral medication developed by Pfizer which acts as an orally active 3C-like protease inhibitor. It is part of a nirmatrelvir/ritonavir combination used to treat COVID-19 and sold under the brand name Paxlovid.
Lufotrelvir (PF-07304814) is an antiviral drug developed by Pfizer which acts as a 3CL protease inhibitor. It is a prodrug with the phosphate group being cleaved in vivo to yield the active agent PF-00835231. Lufotrelvir is in human clinical trials for the treatment of COVID-19, and shows good activity against COVID-19 including several variant strains, but unlike the related drug nirmatrelvir it is not orally active and must be administered by intravenous infusion, and so has been the less favoured candidate for clinical development overall.
