Antiviral Effects of ABMA against Herpes Simplex Virus Type 2 In Vitro and In Vivo

Abstract

Herpes simplex virus type 2 (HSV-2) is the causative pathogen of genital herpes and is closely associated with the occurrence of cervical cancer and human immunodeficiency virus (HIV) infection. The absence of an effective vaccine and the emergence of drug resistance to commonly used nucleoside analogs emphasize the urgent need for alternative antivirals against HSV-2. Recently, ABMA [1-adamantyl (5-bromo-2-methoxybenzyl) amine] has been demonstrated to be an inhibitor of several pathogens exploiting host-vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that ABMA inhibited HSV-2-induced cytopathic effects and plaque formation with 50% effective concentrations of 1.66 and 1.08 μM, respectively. We also preliminarily demonstrated in a time of compound addition assay that ABMA exerted a dual antiviral mechanism by impairing virus entry, as well as the late stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that ABMA protected BALB/c mice from intravaginal HSV-2 challenge with an improved survival rate of 50% at 5 mg/kg (8.33% for the untreated virus infected control). Consequently, our study has identified ABMA as an effective inhibitor of HSV-2, both in vitro and in vivo, for the first time and presents an alternative to nucleoside analogs for HSV-2 infection treatment.

Antiviral effect of Chinese herbal prescription JieZe-1 on adhesion and penetration of VK2/E6E7 with herpes simplex viruses type 2

“…These drugs inhibit the viral DNA polymerase via triphosphorylation, affecting viral replication (Benzekri et al, 2018). However, drug resistance rates are increasing, especially among immunosuppressed individuals (Dai et al, 2018). There is currently no effective HSV-2 vaccine (Churqui et al, 2018), so the exploration of natural plant pharmaceuticals and their active components has become .…”

Trilobatin as an HIV‐1 entry inhibitor targeting the HIV‐1 Gp41 envelope

“…Herpes simplex virus type‐2 is a causative pathogen of genital herpes and is closely associated with HIV infection . Here, we found that trilobatin at high concentrations (458 μ m ) was also effective in inhibiting HSV‐2 infection, suggesting that this compound may also be applicable in those coinfected patients (Fig.…”

Status of antiviral therapeutics against rabies virus and related emerging lyssaviruses

“…Replication of the distantly related respiratory syncytial virus, for instance, is potently blocked by the small-molecule compound RSV604 that is considered to interfere with P-RNP binding [134]. Structural models of RNP and the C-terminal domain of P proteins of both RABV and MOKV revealed close structural homology and interaction mechanism similar to these employed by the related paramyxo-and pneumoviruses [99,[135][136][137][138]. Through yeast-2-hybrid screening, several peptides were identified that bind directly to both RABV and MOKV P in highly conserved regions, inhibiting viral replication in minigenome assays.…”

“…A similar dynamin inhibitor, AMBA, has also shown antiviral effects against HSV, but the selectivity index (SI = CC 50 /EC 50 ) was at a low <21. When tested in vivo, there was only a 50% survival rate of mice given a lethal RABV challenge, greatly compromising therapeutic potential against the RABV indication [99]. Since AMBA was a direct hit compound from a high-throughput screen, synthetic optimization to improve efficacy was suggested.…”