黄芩茎叶提取物与生脉饮抗柯萨奇病毒B3的体外研究

目的：探讨黄芩茎叶提取物及生脉饮体外抗柯萨奇病毒B3（CVB3）的作用。方法：应用细胞感染模型按照药物对Hela细胞及CVB3不同作用方式设直接抗病毒作用组、增强细胞抗病毒作用组、对感染细胞保护作用组及正交设计组。采用光镜观察并结合MTT测定的方法进行综合判断。结果：与病毒对照组比较黄芩茎叶提取物、生脉饮对细胞病变有抑制作用（P〈0．05）。结论：黄芩茎叶提取物、生脉饮均有直接抗病毒作用以及对未感染或已感染Hela细胞的保护作用。生脉饮与黄芩茎叶提取物之间有交互作用。     

抗柯胶囊总皂苷对柯萨奇病毒B型诱导细胞凋亡的抑制作用

目的 观察抗柯胶囊总皂苷抑制柯萨奇病毒B型(CVB)诱导细胞凋亡的作用,探讨其可能的机制。方法 通过接种病毒液的方式建立体外细胞感染模型,采用细胞病变效应法(CPE)测定抗柯胶囊总皂苷对CVB₃、CVB₄、CVB₅株50%抑制浓度(IC₅₀)及治疗指数(TI);CCK-8试剂盒检测细胞存活情况;TdT介导的dUTP缺口末端标记技术(TUNEL法)测定心肌细胞凋亡率;蛋白免疫印迹法(Western-blot)检测大鼠原代心肌细胞中Bcl-2、Bax蛋白表达情况。结果 抗柯胶囊总皂苷可明显抑制CVB₃、CVB₄、CVB₅致细胞病变,对CVB3、CVB4、CVB5的IC50分别为223.34、315.48、306.53μg·mL^-1,治疗指数分别为4.68、3.24、3.24;390.63、195.32、97.66μg·mL^-1剂量组可明显提高3种病毒感染后心肌细胞的存活率,抑制心肌细胞凋亡。抗柯...     

蟾毒内酯抗柯萨奇病毒、腺病毒和流感病毒作用的研究

蟾酥是我国传统的名贵药材,它的主要有效成分是蟾毒内酯,其药理作用很强[1],抗病毒作用至今未见报道.本文对蟾毒内酯抗呼吸道病毒的作用进行了试验研究,结果如下.     

Treatment of herpes simplex virus infections

Herpes simplex virus (HSV) types 1 and 2 are ubiquitous organisms that cause infections in human populations throughout the world. The clinical manifestations of HSV infections are varied, ranging from asymptomatic disease to life-threatening illness in neonates and immunocompromised hosts. This article will review the common presentations for HSV disease and the current recommendations for the treatment of these infections. A detailed summary of the antiviral drugs used to treat HSV infections is also presented.     

Management of mucocutaneous herpes simplex virus infections

Herpes simplex virus type 1 and 2 are causes of common inflammatory conditions of the mucous membranes and skin. The proper management of these infections begins with an accurate diagnosis. Viral cultures should be performed whenever possible. Patients should be counselled regarding the proper care of lesions, the risk of complications, the likelihood of experiencing recurrent infection, and should be urged to avoid intimate contact while lesions are active. Antiviral therapy is now available to ameliorate the symptoms and shorten the duration of infection in selected patients, but does not prevent recurrences. Topical, oral and intravenous preparations of acyclovir are effective in treatment of primary herpes simplex infections. Immunosuppressed patients with herpes simplex infections also benefit from acyclovir therapy. Oral activity has some activity in ameliorating recurrent genital herpes and should be considered for patients who are particularly troubled by their infections.     

Topical treatment of cutaneous herpes simplex virus infections

Topical antiviral chemotherapy has a number of potential advantages over systemic drug delivery for the treatment of cutaneous herpes simplex virus infections, including convenience; higher target tissue drug levels and greater efficacy; and specific targeting of the drug to the site of infection, with reduced cost and reduced exposure of the remainder of the body to drug side effects. Realization of these possibilities has been slow in part because of the paucity of 'active' topical drug formulations with effective penetration-enhancing agents and a technical barrier-our failure as yet to measure drug levels in the epidermis, which could guide formulation development. Recent success with a topical treatment for herpes simplex labialis should stimulate continued laboratory and clinical research in this field.     

Antiviral effect of mangiferin and isomangiferin on herpes simplex virus

Using tissue culture techniques the present study assured us of the merits of mangiferin and isomangiferin in the antiviral action against HSV-1. Utilizing 4 main patterns for evaluating drug effectiveness (ie intratube drug-on-virus direct action, simultaneous addition of drug-virus-inoculum to cell bottle, virus inoculation preceding drug addition, and drug addition followed by virus inoculation), it was readily found by logarithm determination of HSV-I inhibition that isomangiferin was superior to such control drugs as acyclovir, idoxuridine, and cyclocytidine in logarithm by 0.27-0.50, and that mangiferin was lower than isomangiferin in logarithm by 0.53. The average plaque reduction rates of mangiferin and isomangiferin were 69.5% and 56.8%, respectively. All in all, the antiviral effect of mangiferin and isomangiferin was attributed presumably to their capability to inhibit virus replication within cells.     

Novel agents and strategies to treat herpes simplex virus infections

The quiet pandemic of herpes simplex virus (HSV) infection has plagued humanity since ancient times, causing mucocutaneous infection, such as herpes labialis and herpes genitalis. Disease symptoms often interfere with everyday activities and occasionally HSV infections are the cause of life-threatening or sight-impairing disease, especially in neonates and the immunocompromised patient population. After primary or initial infection the virus persists for life in a latent form in neurons of the host, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently, no cure is available. In the mid-1950s the first antiviral, idoxuridine, was developed for topical treatment of herpes disease and, in 1978, vidarabine was licensed for systemic use to treat HSV encephalitis. Acyclovir (Zovirax^®), a potent, specific and tolerable nucleosidic inhibitor of the herpes DNA polymerase, was a milestone in the development of antiviral drugs in the late 1970s. In the mid-1990s, when acyclovir became a generic drug, valacyclovir (Valtrex^®) and famciclovir (Famvir^®), prodrugs of the gold standard and penciclovir (Denavir^®, Vectavir^®), a close analogue, were launched. Though numerous approaches and strategies were tested and considerable effort was expended in the search of the next generation of an antiherpetic therapy, it proved difficult to outperform acyclovir. Notable in this regard was the award of a Nobel Prize in 1988 for the elucidation of mechanistic principles which resulted in the development of new drugs such as acyclovir. Vaccines, interleukins, interferons, therapeutic proteins, antibodies, immunomodulators and small-molecule drugs with specific or nonspecific modes of action lacked either efficacy or the required safety profile to replace the nucleosidic drugs acyclovir, valacyclovir, penciclovir and famciclovir as the first choice of treatment. Recently though, new inhibitors of the HSV helicase-primase with potent in vitro antiherpes activity, novel mechanisms of action, low resistance rates and superior efficacy against HSV in animal models have been discovered. This review summarises the current therapeutic options, discusses the potential of preclinical or investigational drugs and provides an up-to-date interpretation of the challenge to establish novel treatments for herpes simplex disease.     

Novel agents and strategies to treat herpes simplex virus infections

The quiet pandemic of herpes simplex virus (HSV) infection has plagued humanity since ancient times, causing mucocutaneous infection, such as herpes labialis and herpes genitalis. Disease symptoms often interfere with everyday activities and occasionally HSV infections are the cause of life-threatening or sight-impairing disease, especially in neonates and the immunocompromised patient population. After primary or initial infection the virus persists for life in a latent form in neurons of the host, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently, no cure is available. In the mid-1950s the first antiviral, idoxuridine, was developed for topical treatment of herpes disease and, in 1978, vidarabine was licensed for systemic use to treat HSV encephalitis. Acyclovir (Zovirax), a potent, specific and tolerable nucleosidic inhibitor of the herpes DNA polymerase, was a milestone in the development of antiviral drugs in the late 1970s. In the mid-1990s, when acyclovir became a generic drug, valacyclovir (Valtrex) and famciclovir (Famvir), prodrugs of the gold standard and penciclovir (Denavir), Vectavir), a close analogue, were launched. Though numerous approaches and strategies were tested and considerable effort was expended in the search of the next generation of an antiherpetic therapy, it proved difficult to outperform acyclovir. Notable in this regard was the award of a Nobel Prize in 1988 for the elucidation of mechanistic principles which resulted in the development of new drugs such as acyclovir. Vaccines, interleukins, interferons, therapeutic proteins, antibodies, immunomodulators and small-molecule drugs with specific or nonspecific modes of action lacked either efficacy or the required safety profile to replace the nucleosidic drugs acyclovir, valacyclovir, penciclovir and famciclovir as the first choice of treatment. Recently though, new inhibitors of the HSV helicase-primase with potent in vitro antiherpes activity, novel mechanisms of action, low resistance rates and superior efficacy against HSV in animal models have been discovered. This review summarises the current therapeutic options, discusses the potential of preclinical or investigational drugs and provides an up-to-date interpretation of the challenge to establish novel treatments for herpes simplex disease.     

Co-operative thermal inactivation of herpes simplex virus and influenza virus by arginine and NaCl

Elevated temperatures have been used to inactivate viruses for plasma-derived biopharmaceuticals. This paper describes the effects of arginine and NaCl in conjunction with elevated temperature for inactivation of two enveloped viruses, i.e., herpes simplex virus type 1 (HSV-1) and influenza virus type A at neutral pH. In phosphate-buffered saline, a significant inactivation of HSV-1 occurred above 40 degrees C, resulting in less than 10% surviving virus (over 90% virus inactivation) at 50 degrees C. Arginine concentration dependently decreased the temperature required for virus inactivation, leading to temperature shift by almost 17 degrees C at 1.2M. NaCl also decreased the inactivation temperature, but to a considerably lesser extent, indicating that virus inactivation effect of arginine is not simply due to ionic strength. Influenza virus was also inactivated by high temperature, but its responses to arginine and NaCl were different from those on HSV-1, suggesting that virus inactivation mechanism is different between these two viruses, i.e., the effects of these reagents are virus specific.     

Effect of chlordane on influenza type A virus and herpes simplex type 1 virus replication in vitro

The effect of chlordane on the susceptibility of Madin-Darby canine kidney cells and African Green monkey kidney cells to infection with influenza type A/PR/8/34 (HON1) virus and herpes simplex type 1 virus was determined. Exposure of both cell lines to various concentrations of chlordane for 24 h at 37 degrees C (acute exposure) effected a marked reduction in the efficiency of influenza type A virus infection, except at a dose of 0.025 ppm. Acute exposure of the monkey cells did not alter their susceptibility to herpes simplex virus infection. Viral adsorption studies at 4 and 37 degrees C revealed a marked reduction in the attachment of influenza type A virus to both cell lines following acute exposure to 10 ppm chlordane. Viral inactivation studies carried out at 4 and 37 degrees C failed to reveal differences in the level of influenza type A virus inactivation in the presence or absence of chlordane. Madin-Darby canine kidney cells exposed to 10 ppm chlordane for 60 d (chronic exposure) manifested a decrease in the efficiency of influenza type A virus infection, whereas cells chronically exposed to 0.025 ppm chlordane manifested an increase in the efficiency of influenza type A virus infection relative to mock-treated control cells. When chronically exposed cells were passaged six times in the absence of chlordane, these effects were reversed. Viral adsorption studies carried out at 4 and 37 degrees C on cells chronically exposed to 10 ppm chlordane revealed a decrease in the adsorption of influenza type A virus. Quantitation of the levels of cell-surface sialic acid, the essential terminal sugar on the receptor for influenza type A virus, indicated that the reduced adsorption of influenza type A virus to Madin-Darby canine kidney cells was not due to a loss of cell-surface sialic acid. Our findings indicate that chlordane alters the susceptibility of cells to infection with influenza type A virus but not to herpes simplex type 1 virus.     

Experimental protection with tyrothrizin against herpes simplex virus infections in mice

Using 12-day old baby mice, strain NMRI, the LD50 of a Herpes simplex virus type 1 was calculated. Intragastric inoculation of the mice was carried out applying a stomach tube. Lethality of the mice was reduced from 67% to 23% by pre-incubation of the virus suspension for 30 min at 37 degrees C in the presence of 0.2 mg tyrothricin/ml. The effect was statistically significant and could be produced only after direct contact between tyrothricin and virus. Under the same conditions there was no effect of lysozyme against virus infectivity.     

Efficacy of bromovinyldeoxyuridine in the treatment of herpes simplex virus and varicella-zoster virus eye infections

As has been established in rabbits, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) is superior to 5-iodo-2'-deoxyuridine (IDU) in the topical treatment of epithelial HSV-1 (herpes simplex virus type 1) keratitis, and superior to 5-trifluoromethyl-2'-deoxyuridine (TFT) in the topical treatment of deep stromal HSV-1 keratitis and HSV-1 uveitis. BVDU 0.1% eye drops have also proven efficacious in the treatment of patients with dendritic corneal ulcers, geographic corneal ulcers and stromal keratitis, and combined treatment of BVDU 0.1% eye drops with oral BVDU at 375 mg/day for 5 days led to a prompt healing of keratouveitis and skin lesions in patients with ophthalmic herpes zoster.