Antiviral drug for herpes virus

Genital Herpes. Section Navigation. Facebook Twitter LinkedIn Syndicate. Genital Herpes Treatment and Care. Minus Related Pages. Medicine can reduce symptoms and the chance of spreading it to others. Is there a cure or treatment for genital herpes? The NS5A protein in the form of a dimer or multimer localizes to the ER-derived membranes via its amphipathic helix domain.

These NS5A inhibitors efficiently block in vitro and in vivo viral replication, though their exact models of drug actions are yet to be elucidated Ross-Thriepland and Harris, Many experimental NS5A inhibitors such as ravidasvir are still under development. Ravidasvir plus sofosbuvir offered promising virologic response rates in patients infected with HCV genotype 4 Esmat et al.

As a promising drug target, the catalytic site of NS5B is encircled by the finger and thumb domains. The NS5B inhibitors can be mainly divided into either nucleoside inhibitors e. On the one hand, nucleoside inhibitors block the viral RNA synthesis by mimicking natural substrates and competing with incoming nucleoside triphosphates at the catalytic site of NS5B Li and De Clercq, On the other hand, non-nucleotide inhibitors noncompetitively block the allosteric pockets outside the catalytic site to prevent viral RNA synthesis Li and De Clercq, For instance, dasabuvir Kati et al.

Due to its unique features and essential nature, the large polymerase protein has proved to be a promising drug target for the development of nucleoside and non-nucleoside inhibitors.

As of today, ribavirin is an FDA-approved nucleoside inhibitor that inhibits the activity of RSV RdRp, whereas it is largely discontinued to treat RSV infections due to limited efficacy and risk of serious side effects Shook and Lin, RSV fusion glycoprotein is a class I fusion protein that anchors in the membrane of viral particles via a transmembrane domain Gilman et al.

During the viral entry, RSV fusion glycoprotein in the trimeric form is undergoing dramatic changes from the metastable prefusion confirmation to the highly stable post-fusion conformation, thereby driving the fusion of viral membrane with the human cell membranes Gilman et al. RSV fusion glycoprotein that induces RSV-neutralizing antibody responses is a key antigen for protective immunity Tang et al. As a leading target of neutralizing antibodies and vaccines, RSV fusion glycoproteins have conserved sequences across different isolates of RSV type A and B strains Tang et al.

As of September , palivizumab that binds to RSV fusion glycoprotein remains the only monoclonal antibody approved for the prevention of RSV infection in high-risk infants. The UL30 subunit belongs to the B-family of polymerases and forms a typical hand-shaped structure with the catalytic residues D, D located in the palm domain for dNTP polymerization Vashishtha and Kuchta, Due to its indispensable role, the UL30 subunit has been considered as a promising drug target to block viral DNA replication Zarrouk et al.

As of September , many UL30 inhibitors such as idoxuridine, brivudine, trifluridine foscarnet, aciclovir, famciclovir, valaciclovir, and penciclovir have been approved for HSV treatment. Because current compounds face the challenge of drug resistance and adverse reactions Vollmer et al. Antiviral agents such as pritelivir and amenamevir that target HSV helicase-primase complex are still under development Poole and James, Although HSV particles harbor at least 15 envelope proteins, four envelope glycoproteins gD, gB, gH, gL play an indispensable role in viral entry into all permissive cell types Agelidis and Shukla, The viral entry begins with the binding of gD to a human receptor nectin-1, herpesvirus entry mediator, or 3-O-sulfated heparan sulfate Atanasiu et al.

This gD-receptor binding drives the conformation changes in gD to activate the regulatory proteins gH and gL, leading to the activation of gB into a fusogenic state for membrane fusion Agelidis and Shukla, Docosanol n -docosanol; behenyl alcohol is a naturally occurring antiherpetic agent approved by the US FDA as a topical treatment for herpes labialis, as well as the over-the-counter medication for cold sores and fever blisters De Clercq and Li, Although its exact mechanism of action remains unclear, docosanol may inhibit the interactions between HSV envelope proteins and human receptors De Clercq and Li, As of today, cidofovir, ganciclovir, foscarnet, valganciclovir, and fomivirsen discontinued have been approved for HCMV treatment.

UL54 gene is prone to mutations that limit the efficiency of antiviral agents Chou et al. Furthermore, cidofovir may induce nephrotoxicity especially in bone marrow transplant patients Piret et al.

Novel compounds such as CMX brincidofovir are currently under development. CMX can be converted to cidofovir. The drug potency is much higher for CMX than for cidofovir. Cidofovir from CMX does not accumulate in the kidneys, therefore nephrotoxicity could be greatly reduced during the treatment Marty et al. As an indispensable viral protein, UL65 has been considered to be a promising drug target. Subsequently, the PB1 active site undertakes the prime template-directed RNA synthesis, followed by the initiation, elongation, termination, and recycling of typical polymerase activities Wandzik et al.

As a pyrazine derivative, favipiravir received conditional marketing approval only for patients with a novel or reemerging influenza when other antivirals are ineffective because favipiravir increases the risk for teratogenicity and embryotoxicity Takashita, As a cyclohexyl carboxylic acid analog, pimodivir inhibits viral RNA binding by occupying the cap-binding domain of PB2, and it shows strong activity against influenza A but not B viruses Takashita, Other novel polymerase inhibitors are still under development.

Influenza surface glycoprotein neuraminidase is known for its multifunctional roles in viral entry and viral release. During the viral entry, the glycoprotein neuraminidase contributes to the viral binding to the sialic acid receptors of human cell glycoproteins, leading to the enhancement of hemagglutinin receptor binding Wen and Wan, Due to its importance, neuraminidase has been recognized as a promising antiviral target Kumar et al.

As of September , neuraminidase inhibitors such as oseltamivir, zanamivir, peramivir, and laninamivir have been approved for clinical use Table 1. Oseltamivir is used orally as the first-line therapy, but its effectiveness is compromised by the development of drug resistance mutations in influenza A genotypes such as H3N2 and H5N1 Kumar et al.

Due to the emergence of drug resistance, it remains an urgent need to develop anti-influenza agents. Novel antivirals such as A and A are still under development Gubareva and Mohan, The influenza matrix protein 2 M2 is a residue single-pass membrane protein that forms pH-gated proton channels in the viral lipid envelope Schnell and Chou, By shuttling protons inwards and outwards through the viral membrane, matrix protein 2 equilibrates pH across the viral membrane during the viral entry and across the trans-Golgi membrane of host cells during the viral maturation Mandala et al.

Because the channel pore is essential for the proton shuttling, the pore of the M2 channel is a promising drug-binding pocket Gu et al. As of September , rimantadine and amantadine that target the M2 channel pore have been approved for anti-influenza treatment. For instance, amantadine targets the M2 channel by hydrophobic interactions between the adamantane group and the N-terminal gate of the channel Gu et al.

Mutations e. Novel inhibitors that are less prone to mutations may lead to better antiviral efficacy. The extinction of variola virus, the etiological agent of human smallpox was declared by the WHO in Jordan et al. The F13L gene of variola virus encodes a highly conserved 37 kDa peripheral membrane protein called VP Before the viral budding, the wrapping complex requires VP37 and other viral proteins to interact with human membrane proteins; subsequently, it catalyzes the maturation of intracellular viral particles into the egress-competent form of the variola virus particles Jordan et al.

VP37 interacts with human proteins Rab9 and TIP47 a Rab9-specific effector in membrane fractions from infected cells to facilitate assembly of extracellular virus Chen et al. As of September , tecovirimat ST remains the only VP37 inhibitor approved for treating human smallpox, although its effectiveness has only been shown in animal models but not humans due to the extinction of the virus in human populations.

As an 4-trifluoromethyl phenol derivative, tecovirimat blocks the interactions of VP37 with Rab8 and TIP47, thereby inhibiting the maturation of egress-competent enveloped virions for viral budding Jordan et al. Remdesivir acts as a delayed chain terminator to interfere with the RNA synthesis of viral polymerase and evades the proofreading of viral exoribonuclease Eastman et al.

VZV DNA polymerase is an ideal target for the development of nucleoside analogs because it plays a critical role in viral DNA replication during the life cycle.

As of September , nucleoside analogs such as aciclovir, famciclovir, valaciclovir, brivudine, and vidarabine have been approved for VZV treatment De Clercq and Li, As a prodrug of penciclovir, famciclovir effectively prevents the recurrence of VZV, and it has only mild adverse events Wang et al. Furthermore, both aciclovir and famciclovir interventions offer high rates of benefit and showed a similar time to full crusting of lesions Pott Junior et al.

The catalytic site of the polymerase domain is considered as a promising drug target, whilst nucleos t ide inhibitors have been developed to compete with the incorporation of natural nucleotide substrates into the elongating DNA chain, thereby blocking viral DNA synthesis De Clercq and Li, As of September , many nucleos t ide inhibitors entecavir, telbivudine, adefovir dipivoxil, tenofovir disoproxil fumarate, tenofovir alafenamide, clevudine, and besifovir have been approved for clinical use.

Note that clevudine was only approved in South Korea and the Philippines, while besifovir was approved in South Korea. Despite the success of nucleos t ide inhibitors to suppress the viral replication, they do not eliminate the virus from the hepatocytes, and a cure of HBV infection remains yet to be discovered.

Novel HBV polymerase inhibitors such as tenofovir exalidex are still under clinical development Martinez et al. Based on the classification of approved antiviral agents, several features could be summarized. First, antiviral agents mostly target the viral proteins with high specificity, leading to less toxicity compared with human protein targets.

Second, among 9 infectious diseases, the most popular drug targets could be listed as follows: viral polymerase, viral envelope glycoproteins, and viral protease.

These three viral proteins play a dispensable role in viral replication, making them promising viral targets for most human viruses. Compared with monoclonal antibodies and peptides, small molecules are typically cheaper, chemically stabler, structurally simpler and better permeable.

Although this article only describes 10 infectious diseases with approved drugs, future antiviral development should also focus on emerging infectious diseases such as coronaviruses, dengue, Zika, and Ebola. On October 14, , the US FDA approved a mixture of three monoclonal antibodies atoltivimab, maftivimab, odesivimab-ebgn , which marks the first FDA approval for the treatment of Ebola virus infection.

Furthermore, it remains critical improving antivirals to combat emerging drug resistance mutations because drug resistance mutations have been observed in many viruses e. National Center for Biotechnology Information , U. Encyclopedia of Virology. Published online Mar 1. Erik De Clercq. Guest Editor s : Dennis H. Bamford and Mark Zuckerman. Copyright and License information Disclaimer. All rights reserved. Elsevier hereby grants permission to make all its COVIDrelated research that is available on the COVID resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source.

Abstract Over the past 60 years, more than antiviral drugs or their combinations have been approved for clinical use. Glossary Allosteric inhibitors Inhibitors block the enzymatic activity by targeting outside the active site of viral enzymes.

Antiviral drug resistance The reduction in the effectiveness of an antiviral agent to treat an infectious disease, probably caused by amino acid mutations within or outside the drug-binding site. Drug susceptibility The sensitivity of viruses to one or more drugs. The most common antiviral medications used to manage herpes simplex symptoms are available by prescription. They will first diagnose if you have herpes simplex. Then they will prescribe an appropriate medication to manage your symptoms.

Only docosanol Abreva is an antiviral medication available over the counter as a cream to manage oral symptoms such as cold sores or fever blisters.

If you have mild symptoms from a recurring oral herpes infection, you may be able to use nonprescription methods or some home remedies to manage your symptoms.

Before trying over the counter medications or supplements, be sure to talk with your doctor or pharmacist about your symptoms. They will tell you about prescription and nonprescription alternatives to treat your HSV infection. Tell your doctor if you have any serious health conditions including if you have a weakened immune system.

Your doctor will also tell you what you can expect with an HSV infection, how long it may last, and what do to prevent spreading HSV to others while you have an active infection. No, herpes simplex is not curable. But antiviral medications and OTC products are effective at managing symptoms of the condition such as lesions and sores. After your first episode, the virus becomes dormant and may reappear at any time.

Stress, hormonal changes, illness, or sun exposure can trigger an outbreak. Talk with your doctor about steps you can take to minimize outbreaks of herpes simplex.

Most of the approved antiviral medications to treat HSV symptoms are available by prescription. But there are OTC options for repeat episodes of oral herpes. Docosanol Abreva is an OTC option to manage herpes cold sores. Be sure to check with your doctor before taking an OTC medication. A study comparing the antiviral medications acyclovir, famciclovir, penciclovir and valacyclovir to treat herpes simplex labialis oral herpes found all antiviral medications were effective to shorten healing time for lesions and reducing pain.

The comparison study found valacyclovir had the fastest healing time and pain reduction. Yes, even while taking an antiviral medication, you can infect close direct contacts with herpes simplex oral or genital contact while you have sores or blisters.

Take steps to avoid sharing personal hygiene products lip balm, towels, etc. Herpes simplex virus is a common viral infection. And while HSV-2 is less common, in there were around million HSV-2 infections worldwide affecting people aged 15 to 49 years. There is no cure for HSV, but antiviral medications can help reduce painful symptoms.

Most people have mild symptoms that resolve in a few days. Your risk for more serious symptoms is higher if you have a weakened immune system. A healthcare professional can tell you more about the types of HSV infection, and all your treatment options. There are two types of herpes: oral and genital.

Find out what each type of herpes feels like. If you think you may have herpes, see a doctor as soon…. Do you have sores near your mouth or persistent itchiness in your groin area?