Receptors and ligands for herpes simplex viruses: Novel insights for drug targeting

Huang, Yiwei; Song, Yuyun; Li, Jichen; Lv, Changning; Chen, Zhe‐Sheng; Liu, Zhijun

doi:10.1016/j.drudis.2021.10.004

Cited by 14 publications

(18 citation statements)

References 97 publications

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“…Heparin/heparan sulfate (Hp/HS), two members of the superfamily of glycosaminoglycans (GAGs), play important roles in numerous molecular and cellular processes. Classically, Hp/HS have been studied extensively as modulators of coagulation; however, growing evidence indicates that these biopolymers may possess major clinical value as anti-infectives and anti-cancer agents [1] , [2] , [3] , [4] . Hp/HS have also been implicated as major regulators in diverse processes such as axonal growth [5] , neurofibrillary tangles [6] , and native immune response [7] , [8] .…”

Section: Introductionmentioning

confidence: 99%

3-O-Sulfation induces sequence-specific compact topologies in heparan sulfate that encode a dynamic sulfation code

Holmes

Nagarajan

Desai

2022

Computational and Structural Biotechnology Journal

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Section: Introductionmentioning

confidence: 99%

3-O-Sulfation induces sequence-specific compact topologies in heparan sulfate that encode a dynamic sulfation code

Holmes

Nagarajan

Desai

2022

Computational and Structural Biotechnology Journal

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“…The binding of glycoprotein D with one of its receptors triggered the ability of gB to cause membrane fusion, and the gD determined the tropism of the HSV to the host cells. The inhibition of the membrane fusion process was a promising strategy for combating infection [ 50 ]. It was found by QPCR assay that quercetin, corilagin, and geraniin could attenuate the expression of HSV-2 gD and VP16 at the transcription gene level.…”

Section: Discussionmentioning

confidence: 99%

Antiviral Effect of Polyphenolic Substances in Geranium wilfordii Maxim against HSV-2 Infection Using in vitro and in silico Approaches

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Herpes simplex virus type 2 (HSV-2) infestation was the most widespread STD (sexually transmitted diseases) among humans and was the leading cause of infectious recurrent genital herpes. Existing therapies against HSV-2 did incompletely restrain the comeback of activated HSV-2 infestation. Geranium wilfordii Maxim had long been used as traditional Chinese medicine for treating the diseases owing to its anti-inflammatory and antiviral effects. Herein, the study was designed to investigate the antiviral activity of G.wilfordii and its potential effect in regulating the host’s immune response. Methods. To identify the stage of infection at which the compounds inhibited HSV-2, we performed virucidal, therapeutic, and prophylactic assays. The antiviral efficacy was evaluated by the analysis of viral components HSV-2 gD and VP16. The antiviral activities of these compounds were also evaluated by phenotypic analysis, such as cell proliferation and apoptosis. Molecular docking studies on candidate compounds were done to indicate binding interactions between the compounds and adopted compound targets. Results. Quercetin, corilagin, and geraniin inhibited the replication of HSV-2, with geraniin showing greater TI. The obtained IC50 value of quercetin was 204.7 μM and TI (IC50/EC50) was 5.1, whereas the obtained IC50 value of corilagin was 118.0 μg/ml and TI was 4.05. Geraniin exhibited prominent antiviral activity with an IC50 of 212.4 μM and an EC50 of 18.37 μM, resulting in a therapeutic index (TI) of 11.56. Geraniin showed important in vitro virucidal activity through blocking viral attachment. Compared with the virus group, the apoptosis rates in quercetin-, corilagin-, and geraniin-treated groups were significantly decreased ( p < 0.001 ).The expressions at the transcription genes of virus own replication key factors (including HSV-2 gD and VP16) and cytokines (including TBK1) of infected cells treated with quercetin, corilagin, and geraniin were inhibited. The in silico approaches demonstrated a high number of potential strong intermolecular interactions as hydrogen bonds between geraniin, corilagin, and the activity site of HSV-2 gD. Molecular docking studies demonstrated the effects of corilagin by targeting TBK1. Conclusions. Together, these results highlighted the importance of G.wilfordii treatment in HSV-2 infection and underscored its therapeutic potential. However, additional in vitro and in vivo research was required to validate our findings.

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“…According to the World Health Organization, more than 3.7 billion people worldwide suffer from HSV infections, particularly HSV-1 [ 69 ]. HSV, a prototype human alpha-herpesvirus, is categorized into two types, HSV-1 and HSV-2 [ 70 ]. HSV-1 causes oral herpes with the ability to induce genital herpes and is mainly transmitted by oral-to-oral contact, while HSV-2 is a sexually transmitted disease that primarily generates genital herpes.…”

Section: Flavonoids Target Human Herpesviruses Of the Nervous Systemmentioning

confidence: 99%

Flavonoids Target Human Herpesviruses That Infect the Nervous System: Mechanisms of Action and Therapeutic Insights

Šudomová¹,

Berchová‐Bímová

Mazuráková

et al. 2022

Viruses

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Human herpesviruses (HHVs) are large DNA viruses with highly infectious characteristics. HHVs can induce lytic and latent infections in their host, and most of these viruses are neurotropic, with the capacity to generate severe and chronic neurological diseases of the peripheral nervous system (PNS) and central nervous system (CNS). Treatment of HHV infections based on strategies that include natural products-derived drugs is one of the most rapidly developing fields of modern medicine. Therefore, in this paper, we lend insights into the recent advances that have been achieved during the past five years in utilizing flavonoids as promising natural drugs for the treatment of HHVs infections of the nervous system such as alpha-herpesviruses (herpes simplex virus type 1, type 2, and varicella-zoster virus), beta-herpesviruses (human cytomegalovirus), and gamma-herpesviruses (Epstein–Barr virus and Kaposi sarcoma-associated herpesvirus). The neurological complications associated with infections induced by the reviewed herpesviruses are emphasized. Additionally, this work covers all possible mechanisms and pathways by which flavonoids induce promising therapeutic actions against the above-mentioned herpesviruses.

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Receptors and ligands for herpes simplex viruses: Novel insights for drug targeting

Cited by 14 publications

References 97 publications

3-O-Sulfation induces sequence-specific compact topologies in heparan sulfate that encode a dynamic sulfation code

3-O-Sulfation induces sequence-specific compact topologies in heparan sulfate that encode a dynamic sulfation code

Antiviral Effect of Polyphenolic Substances in Geranium wilfordii Maxim against HSV-2 Infection Using in vitro and in silico Approaches

Flavonoids Target Human Herpesviruses That Infect the Nervous System: Mechanisms of Action and Therapeutic Insights

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