Herpes simplex Virus (HSV)

CAS No.	Product Name	Inquiry
78582-17-9	3-Deaza-2'-deoxyadenosine It has a strong inhibitory effect on lymphocyte-mediated cytolysis, but has low cytotoxicity at 100 μM. This nucleoside can also be used to evaluate the role of adenine N3 nitrogen in DNA structure and function.
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80685-22-9	9-Carboxymethoxymethylguanine 9-Carboxymethoxymethylguanine is the main metabolite of Aciclovir, which is an orally active antiviral drug.
82410-32-0	Ganciclovir Ganciclovir is an antiviral drug for feline herpesvirus type-1 with IC50 of 5.2 μM.
84558-93-0	Netivudine Netivudine, a nucleoside analogue, has potent anti-varicella zoster virus activity.
867-44-7	S-Methylisothiourea hemisulfate salt (S)-Methylisothiourea sulfate is a more potent than NMMA as an inhibitor of inducible nitric oxide synthetase (iNOS). The Ki values are 120, 200, and 160 nM using purified human iNOS, eNOS, and nNOS, respectively.
873061-79-1	Ganoderone A
88546-96-7	Minumicrolin Minumicrolin isolated from the herbs of Murraya exotica L.
88901-43-3	Mogroside III-A2 Mogroside III-A2 is found in Siraitia grosvenorii.
89419-23-8	Antiviral agent 47
896106-16-4	Imiquimod maleate Imiquimod maleate is an immune response modifier. It acts as a toll-like receptor 7 agonist. It is commonly used topically to treat warts on the skin of the genital and anal areas. It is also used to treat certain diseases of the skin, including skin cancers, such as basal cell carcinoma, Bowen's disease, superficial squamous cell carcinoma, some superficial malignant melanomas, and actinic keratosis. It can lead to the activation of Langerhans cells, which subsequently migrate to local lymph nodes to activate the adaptive immune system when applied to skin.
9061-39-6	Galactofucan Galactofucan (Fucogalactan) is a sulfated polysaccharide. Galactofucan can be extracted from brown seaweed Saccharina longicruris with anticoagulant, anti-tumor, anti-thrombosis, anti-inflammatory and antiviral properties. Galactofucan shows antiviral activities to HSV-1 and HSV-2 with IC50s of 0.76 and 1.34 µg/mL, respectively. Galactofucan can be used for the research of cancer and inflammation.
908112-37-8	AT-533
936541-36-5	Lactoferrin
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957890-42-5	HIV-1 integrase inhibitor 2 HIV-1 integrase inhibitor 2 is useful for anti-HIV, which can target HIV-1 integrase and depress the activity in the treatment of HIV infection, AIDS, and other similar diseases characterized by integration of a retroviral genome into a host chromosome. It did not affect integrase-DNA binding and only weakly inhibited the catalytic activities of integrase.
96412-41-8	Guanosine-8-d Guanosine-8-d is a deuterium labeled Guanosine. Guanosine is a purine nucleoside comprising guanine attached to a ribose(ribofuranose) ring via a β-N9-glycosidic bond. Guanosine possesses anti-HSV activity.
97845-62-0	Penciclovir sodium Penciclovir (VSA 671) sodium is a potent and selective anti-herpesvirus agent with EC50 values of 0.5, 0.8 µg/ml for HSV-1 (HFEM), HSV-2 (MS), respectively. Penciclovir sodium shows anti-herpesvirus activity with no-toxic. Penciclovir sodium preventes mortality in mouse
99011-78-6	Imiquimod hydrochloride Imiquimod hydrochloride is an immune response modifier. It acts as a toll-like receptor 7 agonist. It is commonly used topically to treat warts on the skin of the genital and anal areas. It is also used to treat certain diseases of the skin, including skin cancers, such as basal cell carcinoma, Bowen's disease, superficial squamous cell carcinoma, some superficial malignant melanomas, and actinic keratosis. It can lead to the activation of Langerhans cells, which subsequently migrate to local lymph nodes to activate the adaptive immune system when applied to skin.
16595-80-5	Levamisole hydrochloride Levamisole hydrochloride, the hydrochloride salt of a water-soluble imidazothiazole derivative, selectively activates acetylcholine receptor ion channels in nerve and muscle of nematodes (EC50 = 6 µM). It has anthelminthic and immunomodulating activities.

What is Herpes simplex Virus (HSV)?

Herpes simplex virus (HSV) is a linear double-stranded DNA virus belonging to the α subfamily of the family Herpesviridae, one of the earliest discovered human herpesviruses, is a neurotropic double-stranded DNA envelope virus, which survives in large numbers in nature, can invade human and animal bodies and cause infection, the virus usually infects the body through mucous membranes, skin, nervous tissues, etc. and causes related lesions, and herpes simplex caused by its infection is a common infectious skin disease.

Herpes simplex Virus structure

Herpes simplex virus is spherical in shape, and the intact virus consists of a core, capsid, tegument, and envelope, and the core contains double-stranded DNA, which is wound into a filament reel. The capsid is icosahedral symmetrical, composed of 162 shell particles, and has a diameter of 100 nm. The outer layer of the capsid is covered by a membrane with uneven thickness, and the outermost layer is a typical lipid bilayer capsule with protrusions. The diameter of the enveloped virus is 150~200nm. The surface of the envelope contains gb, gC, gD, gE, gG, and gH glycoproteins, which are related to virus adsorption/penetration into cells (gB, gC, gD, gE), control of virus budding release (gH) from the nuclear membrane, and induction of cell fusion (gb gC gD gH). It also has induced neutralizing antibodies (the strongest gd) and cytotoxic effects (known HSV glycoproteins).

Type of Herpes simplex Virus

The seroprevalence of HSV-1 and HSV-2 in the population is 68% and 22%, respectively. HSV-1 is one of the most prevalent viral infections in the world, with a seropositivity rate of more than 85% in adults and even 100% in some countries and regions. According to statistics, 90% of the causative agents of genital herpes are HSV-2 and only 10% are HSV-1. It is estimated that 20% of people worldwide are HSV-2 positive, and the incidence is increasing by about 25% every year.

It is important to note that infections caused by HSV-1 and HSV-2 have different manifestations, but there is no absolute boundary. HSV-1 is mainly transmitted through oral contact, causing infections in or around the mouth (such as oral herpes or cold sores), but a few can cause genital herpes. HSV-2 is mainly transmitted through sexual contact and causes genital herpes. Most infected people have no symptoms or only mild symptoms, and HSV-2 infection can cause painful blisters or sores that may recur over time.

Herpes simplex Virus stages

Depending on the characteristic gene expression, herpesvirus infection hosts present two types of infection processes, namely the incubation phase and the lysis phase. During the incubation period, the viral genome is cyclized within the cell and bound to the chromosome in the form of episomes. No virus particles are produced during this period, and only a small fraction of genes are expressed.

Under external stimuli, the herpes virus can enter the lysis phase from the incubation period. During the lysis phase, de novo infected virus first binds to receptors on the surface of the host cell membrane through glycoproteins on the envelope, and subsequently enters the cell through fusion of the viral envelope with the cell membrane. After the viral particle enters the cell, some of the mesenchymal proteins are dissociated from the nucleocapsid, which is transported through microtubules near the nucleus, and the viral genomic DNA is released into the nucleus through the nuclear pore. Genomic DNA replication and viral protein expression are carried out in the nucleus, and the viral genome is packaged and assembled into a new nucleocapsid. The assembled nucleocapsid needs to cross two layers of nuclear membrane with the assistance of the nuclear release complex (NEC) and thus enter the cytoplasm. The viral particles then acquire interstitial proteins and envelopes in the cytoplasm for further maturation. Finally, mature viral particles are released outside the cell by exocytosis and infect other cells.

Fig.1 Diagram of the HSV replication cycle. Fig.1 Overview of the herpes virus replication cycle. (Draganova Elizabeth B., et al., 2021)

Triggers for HSV

Cold: When a cold occurs, the body's immunity is weakened, and the latent virus multiplies and is active, invading important parts of the body to induce herpes simplex virus infection.

Use of immunosuppressive drugs: It can suppress the body's immune mechanism, causing the body's immunity to decrease, causing herpes simplex.

Trauma: When trauma occurs, the body's resistance is weakened and is not enough to resist the invasion of the virus, causing the virus to spread in the body and induce herpes simplex.

Herpes simplex Virus infection route

The transmission route of herpes simplex virus mainly includes airborne transmission, as well as close contact transmission, sexual contact transmission, and mother-to-child transmission.

Saliva: Saliva is one of the most common forms of infection among many infectious diseases, and in the herpes simplex virus, it can also be transmitted through saliva, through the virus to carry talking, arguing, etc., once the saliva is in contact with the body without the disease, then it is possible to be infected by the herpes simplex virus.

Contact: For this type of contact, it is often aimed at relatives and friends around the patient, especially some physical contact is the most likely way to be transmitted by herpes simplex virus, so once infected with herpes simplex virus, then be careful not to make close contact with others to prevent infecting others.

Sexual life: For sexual life, the main target is herpes simplex virus type 2, because for herpes simplex virus type 1, there is no sexual infection, and type 2 can also be regarded as this sexually transmitted disease, and the infection of this type of infection is very large.

Herpes simplex Virus treatment

Treatment of herpes simplex virus (HSV) consists mainly of antiviral drugs, topical therapy, and supportive care. The following are common treatments:

Antiviral therapy

Acyclovir: Acyclovir is a commonly used antiviral drug that is widely used to treat a variety of viral infections. The drug can be administered orally, intravenously or topically to reduce symptoms and shorten the course of the disease. The main mechanism of acyclovir is to inhibit viral reproduction and transmission by inhibiting viral DNA polymerase, thus preventing viral DNA replication.

Valacyclovir: Valacyclovir is a prodrug of acyclovir that is rapidly converted to acyclovir in the body when taken orally. Valacyclovir has better bioavailability than direct acyclovir, meaning it is more fully absorbed in the body and more effective. It is mainly used to treat infections caused by herpes simplex virus (HSV) and herpes zoster virus (VZV).

Famciclovir: Famciclovir is another antiviral drug used to treat herpes simplex virus infection and can be given by mouth. After being converted into an active metabolite in vivo, famciclovir works by inhibiting viral DNA polymerase. The drug is commonly used to treat acute herpes zoster and recurrent genital herpes and helps reduce symptoms and shorten the duration of the disease.

Topical treatments

Topical antiviral creams: Acyclovir creams, such as acyclovir creams, can be applied directly to the affected area to effectively relieve local symptoms and promote healing. Acyclovir ointment reduces pain and discomfort by inhibiting viral DNA synthesis and reducing the number of viruses.

Local anesthetics: Lidocaine gel, for example, can be used for pain and discomfort caused by herpes infection. Lidocaine is a local anesthetic that reduces pain by blocking nerve signals, making patients more comfortable during treatment.

Supportive care

Keep the affected area clean and dry to prevent secondary infection. Avoid irritating substances such as spicy foods, alcohol and tobacco to reduce irritation to the affected area. Use painkillers, such as ibuprofen or acetaminophen, to reduce pain and inflammation.

As neurotropic and neuroinvasive viruses, HSV-1 and HSV-2 persist in the body through the immune system that is latent and hidden in the neuronal cell body. Currently, drugs are being developed that target different stages of herpes virus replication. There are several drugs that target herpesvirus DNA replication, including non-nucleoside inhibitors of viral DNA polymerase and helicase-primase inhibitors, that show considerable promise.

References

Cole, Shannon. Herpes simplex virus: epidemiology, diagnosis, and treatment. Nursing Clinics 55.3 (2020): 337-345.
Draganova, Elizabeth B., et al., Heldwein. The ins and outs of herpesviral capsids: divergent structures and assembly mechanisms across the three subfamilies. Viruses 13.10 (2021): 1913.

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