Broad-spectrum antiviral drug

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Broad-spectrum antivirals (BSAs) are a class of molecules or compounds, which inhibit the replication of a broad range of viruses (i.e. viruses belonging to two or more viral families). BSAs could be divided into experimental and investigational agents, and approved drugs. BSAs work by inhibiting viral proteins (such as polymerases and proteases) or by targeting host cell factors and processes exploited by different viruses during infection. [1] As of 2021, there are 150 known BSAs in varying stages of development, effective against 78 human viruses. [2] BSAs are potential candidates for treatment of emerging and re-emerging viruses, such as ebola, marburg, and SARS-CoV-2. [3] [4] Many BSAs show antiviral activity against other viruses than originally investigated (such as remdesivir and interferon alpha). Efforts in drug repurposing for SARS-CoV-2 is currently underway. A database of BSAs and viruses they inhibit could be found here (https://drugvirus.info/).

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<span class="mw-page-title-main">Antiviral drug</span> Medication used to treat a viral infection

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.

<span class="mw-page-title-main">Ribavirin</span> Antiviral medication

Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a. Among the viral hemorrhagic fevers it is used for Lassa fever, Crimean–Congo hemorrhagic fever, and Hantavirus infection but should not be used for Ebola or Marburg infections. Ribavirin is taken by mouth or inhaled.

Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS and hepatitis C. These protease inhibitors prevent viral replication by selectively binding to viral proteases and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.

<span class="mw-page-title-main">Umifenovir</span> Chemical compound

Umifenovir, sold under the brand name Arbidol, is an antiviral medication for the treatment of influenza and COVID infections used in Russia and China. The drug is manufactured by Pharmstandard. It is not approved by the U.S. Food and Drug Administration (FDA) for the treatment or prevention of influenza.

<span class="mw-page-title-main">Nitazoxanide</span>

Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.

<span class="mw-page-title-main">Griffithsin</span>

Griffithsin is a protein isolated from the red algae Griffithsia. It has a 121-amino acid sequence which exhibits a Jacalin-like lectin fold. Several structures of this protein have been solved by X-ray crystallography and deposited in the PDB. It has been shown in vitro to be a highly potent HIV entry inhibitor. It is currently being investigated as a potential microbicide for use in the prevention of the transmission of HIV.

A virucide is any physical or chemical agent that deactivates or destroys viruses. The substances are not only virucidal but can be also bactericidal, fungicidal, sporicidal or tuberculocidal.

<span class="mw-page-title-main">FGI-104</span>

FGI-104 is the name of an experimental broad-spectrum antiviral drug, with activity against a range of viruses including hepatitis B, hepatitis C, HIV, Ebola virus, and Venezuelan equine encephalitis virus.

<span class="mw-page-title-main">3C-like protease</span> Class of enzymes

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.

<span class="mw-page-title-main">Favipiravir</span> Experimental antiviral drug with potential activity against RNA viruses

Favipiravir, sold under the brand name Avigan among others, is an antiviral medication used to treat influenza in Japan. It is also being studied to treat a number of other viral infections, including SARS-CoV-2. Like the experimental antiviral drugs T-1105 and T-1106, it is a pyrazinecarboxamide derivative.

<span class="mw-page-title-main">MK-608</span> Chemical compound

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.

<span class="mw-page-title-main">NITD008</span> Chemical compound

NITD008 is an antiviral drug classified as an adenosine analog. It was developed as a potential treatment for flavivirus infections and shows broad spectrum antiviral activity against many related viruses such as dengue virus, West Nile virus, yellow fever virus, Powassan virus, hepatitis C virus, Kyasanur Forest disease virus, Omsk hemorrhagic fever virus, and Zika virus. However, NITD008 proved too toxic in pre-clinical animal testing to be suitable for human trials, but it continues to be used in research to find improved treatments for emerging viral diseases.

<span class="mw-page-title-main">EICAR (antiviral)</span> Chemical compound

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.

<span class="mw-page-title-main">COVID-19 drug repurposing research</span> Drug repurposing research related to COVID-19

Drug repositioning is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed. This is one line of scientific research which is being pursued to develop safe and effective COVID-19 treatments. Other research directions include the development of a COVID-19 vaccine and convalescent plasma transfusion.

<span class="mw-page-title-main">COVID-19 drug development</span> Preventative and therapeutic medications for COVID-19 infection

COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research, with 419 potential COVID-19 drugs in clinical trials, as of April 2021.

<span class="mw-page-title-main">3CLpro-1</span>

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.

<span class="mw-page-title-main">GC376</span> Broad-spectrum antiviral medication

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.

<span class="mw-page-title-main">IDX-184</span>

IDX-184 is an antiviral drug which was developed as a treatment for hepatitis C, acting as a NS5B RNA polymerase inhibitor. While it showed reasonable effectiveness in early clinical trials it did not progress past Phase IIb. However research using this drug has continued as it shows potentially useful activity against other emerging viral diseases such as Zika virus, and coronaviruses including MERS, and SARS-CoV-2.

<span class="mw-page-title-main">GS-441524</span>

GS-441524 is a nucleoside analogue antiviral drug which was developed by Gilead Sciences. It is the main plasma metabolite of the antiviral prodrug remdesivir, and has a half-life of around 24 hours in human patients. Remdesivir and GS-441524 were both found to be effective in vitro against feline coronavirus strains responsible for feline infectious peritonitis (FIP), a lethal systemic disease affecting domestic cats. Remdesivir was never tested in cats, but GS-441524 has been found to be effective treatment for FIP and is widely used despite no official FDA approval due to Gilead's refusal to license this drug for veterinary use. An isopropylester pro-drug of GS-441524 - Obeldesivir has been developed by GILEAD Sciences and is in Phase III clinical trials. A deuterated form has been developed by Vigonvita Life Sciences and is also in Phase III clinical trials.

COVID Moonshot is a collaborative open-science project started in March 2020 with the goal of developing an un-patented oral antiviral drug to treat SARS-CoV-2, the virus causing COVID-19. COVID Moonshot researchers are targeting the proteins needed to form functioning new viral proteins. They are particularly interested in proteases such as 3C-like protease (Mpro), a coronavirus nonstructural protein that mediates the breaking and replication of proteins.

References

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  2. "DrugVirus.info". drugvirus.info. Retrieved 2020-03-28.
  3. García-Serradilla M, Risco C, Pacheco B (April 2019). "Drug repurposing for new, efficient, broad spectrum antivirals". Virus Research. 264: 22–31. doi:10.1016/j.virusres.2019.02.011. PMC   7114681 . PMID   30794895.
  4. Andersen PI, Ianevski A, Lysvand H, Vitkauskiene A, Oksenych V, Bjørås M, et al. (April 2020). "Discovery and development of safe-in-man broad-spectrum antiviral agents". International Journal of Infectious Diseases. 93: 268–276. doi: 10.1016/j.ijid.2020.02.018 . PMC   7128205 . PMID   32081774.