NSC23766 and Ehop016 Suppress Herpes Simplex Virus-1 Replication by Inhibiting Rac1 Activity

Zhang, Fang; Liu, Ye; You, Qiao; Yang, Enhui; Liu, Bingxin; Wang, Huanru; Xu, Shiqi; Nawaz, Waqas; Chen, Deyan; Wu, Zhiwei

doi:10.1248/bpb.b21-00054

Cited by 10 publications

(8 citation statements)

References 47 publications

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“…Graber et al and our present study published in the Biological and Pharmaceutical Bulletin showed that HSV-1 infection upregulated Rac1 activity to support its replication ( 35 , 36 ). In addition, a previous study has shown that 6-TG mediated immunosuppressive effects by interfering with Rac1 protein function ( 20 ).…”

Section: Resultssupporting

confidence: 57%

6-Thioguanine Inhibits Herpes Simplex Virus 1 Infection of Eyes

et al. 2021

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We reported the discovery of 6-TG inhibition of HSV-1 infection and its inhibitory roles in HSK both in vitro and in vivo . 6-TG was shown to possess at least 10× more potent inhibitory activity against HSV-1 than ACV and GCV and, more importantly, inhibit ACV/GCV-resistant mutant viruses. Animal model studies showed that gel-formulated 6-TG topically applied to eyes locally infected with HSV-1 could significantly inhibit HSV-1 replication, alleviate virus-induced HSK pathogenesis, and improve eye conditions.

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Section: Resultssupporting

confidence: 57%

6-Thioguanine Inhibits Herpes Simplex Virus 1 Infection of Eyes

et al. 2021

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“…When determining the effectiveness of the proposed interventions, five (3.65%) were shown not to be effective [84,107,126,131,139], three (2.19%) were somewhat effective [21,46,53], and 128 (93.43%) were effective as potential managements for resistant strains of HSV [1][2][3][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][47][48][49][50][51][52][54][55][56][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122]…”

Section: Data Extractionmentioning

confidence: 99%

A Systematic Review of Second-Line Treatments in Antiviral Resistant Strains of HSV-1, HSV-2, and VZV

Lince¹,

DeMario²,

Yang³

et al. 2023

Cureus

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Drug-resistant variants of herpes simplex viruses (HSV) have been reported that are not effectively treated with first-line antiviral agents. The objective of this study was to evaluate available literature on the possible efficacy of second-line treatments in HSV and the use of second-line treatments in HSV strains that are resistant to first-line treatments. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a final search was conducted in six databases on November 5, 2021 for all relevant literature using terms related to antiviral resistance, herpes, and HSV. Eligible manuscripts were required to report the presence of an existing or proposed second-line treatment for HSV-1, HSV-2, or varicella zoster virus (VZV); have full-text English-language access; and potentially reduce the rate of antiviral resistance. Following screening, 137 articles were included in qualitative synthesis. Of the included studies, articles that examined the relationship between viral resistance to first-line treatments and potential second-line treatments in HSV were included. The Cochrane risk-of-bias tool for randomized trials was used to assess risk of bias. Due to the heterogeneity of study designs, a meta-analysis of the studies was not performed. The dates in which accepted studies were published spanned from 2015-2021. In terms of sample characteristics, the majority (72.26%) of studies used Vero cells. When looking at the viruses on which the interventions were tested, the majority (84.67%) used HSV-1, with (34.31%) of these studies reporting testing on resistant HSV strains. Regarding the effectiveness of the proposed interventions, 91.97% were effective as potential managements for resistant strains of HSV. Of the papers reviewed, nectin in 2.19% of the reviews had efficacy as a second-line treatments in HSV, amenamevir in 2.19%, methanol extract in 2.19%, monoclonal antibodies in 1.46%, arbidol in 1.46%, siRNA swarms in 1.46%, Cucumis melo sulfated pectin in 1.46%, and components from Olea europeae in 1.46%. In addition to this griffithsin in 1.46% was effective, Morus alba L. in 1.46%, using nucleosides in 1.46%, botryosphaeran in 1.46%, monoterpenes in 1.46%, almond skin extracts in 1.46%, bortezomib in 1.46%, flavonoid compounds in 1.46%, andessential oils were effective in 1.46%, but not effective in 0.73%. The available literature reviewed consistently supports the existence and potentiality of second-line treatments for HSV strains that are resistant to first-line treatments. Immunocompromised patients have been noted to be the population most often affected by drug-resistant variants of HSV. Subsequently, we found that HSV infections in this patient population are challenging to manage clinically effectively. The goal of this systematic review is to provide additional information to patients on the potentiality of second-line treatment in HSV strains resistant to first-line treatments, especially those who are immunocompromised. All patients,...

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“…Harringtonine is a natural alkaloid and homolog which exhibits antitumor activities, giving for its use in leukemia. Its mechanism of action is that it blocks peptide bond formation and aminoacyl-tRNA binding, ultimately preventing protein synthesis ( Table 3 ) [ 108 ]. More recently, its antiviral effects have been recognized, particularly against chikungunya virus [ 109 ], Singapore grouper iridovirus [ 110 ], varicella-zoster virus [ 111 ], and Zika virus [ 112 ].…”

Section: Clinical Management Of Hsv Keratitismentioning

confidence: 99%

“…This was accomplished by harringtonine’s ability to suppress the herpes virus entry mediator expression, thus preventing viral entry of HSV-1 [ 9 ]. Finally, in 2021, Zhang et al found that Ras-related C3 botulinum toxin substrate 1 could be a novel therapeutic target against HSV-1 [ 108 ].…”

Section: Clinical Management Of Hsv Keratitismentioning

confidence: 99%

Clinical Management of Herpes Simplex Virus Keratitis

Labib

Chigbu

2022

Diagnostics

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Herpes simplex virus (HSV) keratitis is one of the leading causes of blindness worldwide. Additionally, up to 90% of the population in some countries is seropositive for HSV. HSV can cause a wide spectrum of ocular disease ranging from blepharitis to retinitis. Although the initial clinical expressions of HSV-1 and HSV-2 are similar, HSV-2 has been reported more frequently in association with recurrent HSV disease. Besides irreversible vision loss from keratitis, HSV also causes encephalitis and genital forms of the disease. Despite these statistics, there remains no vaccine against HSV. Current treatment therapies for related ocular diseases include the use of oral and topical antivirals and topical corticosteroids. While effective in many cases, they fail to address the latency and elimination of the virus, making it ineffective in addressing recurrences, a factor which increases the risk of vision loss. As such, there is a need for continued research of other potential therapeutic targets. This review utilized several published articles regarding the manifestations of HSV keratitis, antiviral immune responses to HSV infection, and clinical management of HSV keratitis. This review will summarize the current knowledge on the host–virus interaction in HSV infections, as well as highlighting the current and potential antiviral therapeutics.

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NSC23766 and Ehop016 Suppress Herpes Simplex Virus-1 Replication by Inhibiting Rac1 Activity

Cited by 10 publications

References 47 publications

6-Thioguanine Inhibits Herpes Simplex Virus 1 Infection of Eyes

6-Thioguanine Inhibits Herpes Simplex Virus 1 Infection of Eyes

A Systematic Review of Second-Line Treatments in Antiviral Resistant Strains of HSV-1, HSV-2, and VZV

Clinical Management of Herpes Simplex Virus Keratitis

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