Evaluation of (S)-10-Hydroxycamptothecin Inhibitor of Herpes Simplex Type 1 Identified from Screening of a Library of Natural Products

Message:
Article Type:
Research/Original Article (دارای رتبه معتبر)
Abstract:
Background

 Herpes simplex virus type 1 (HSV-1) causes serious illness in humans, especially in newborns and immunocompromised hosts. Public health requires the development of new, less toxic anti-HSV-1 drugs.

Objectives

 This study aimed to evaluate the potential anti-herpesvirus activity of natural products in an extensive library of 133 compounds by examining viral titers and the number of viral plaques.

Methods

 (S)-10-hydroxycamptothecin (10-HCPT) as an inhibitor against viral DNA replication in the lowest concentration ranges from a set of natural products consisting of screening 133 compounds. Each step of the viral replication cycle of HSV-1 on A549 cells was evaluated with different assays, including adsorption, penetration, time-of-addition assay, and quantitative polymerase chain reaction (PCR). The respective antiviral effects on HSV-1AN95 infection were assessed in vitro.

Results

 10-HCPT was found to be a potent inhibitor of HSV-1 infection in the lowest concentration range from screening of a natural product library. The results showed that 10-HCPT significantly affects HSV-1 viral plaque formation inhibition, with a half maximal effective concentration (EC50) of 0.07 μM. The time of addition assay suggested that 10-HCPT had a viral inhibitory effect when added 8 hours after infection. It was further confirmed by reducing the expression of late viral genes including glycoprotein (g) and viral protein (VP) (gB, gD, gH, VP1/2, and VP16) 4 hours after infection in the 10-HCPT treatment group compared to positive controls by quantitative real-time PCR. The Western blotting results are inconsistent with other reported results. It showed that 10-HCPT did not affect gD and ICP4 during HSV-1 infection, and 10-HCPT appeared to affect other genes in the immediate-early (IE) and late (L) steps.

Conclusions

 10-HCPT demonstrated anti-HSV activity on HSV-1. Their dose-dependent antiviral activity showed that specific cellular components might mediate their function rather than cytotoxicity. This survey suggests a new outlook in exploring effective treatment options for HSV-1 infections.

Language:
English
Published:
Jundishapur Journal of Microbiology, Volume:15 Issue: 10, Oct 2022
Page:
2
https://magiran.com/p2519976  
دانلود و مطالعه متن این مقاله با یکی از روشهای زیر امکان پذیر است:
اشتراک شخصی
با عضویت و پرداخت آنلاین حق اشتراک یک‌ساله به مبلغ 1,390,000ريال می‌توانید 70 عنوان مطلب دانلود کنید!
اشتراک سازمانی
به کتابخانه دانشگاه یا محل کار خود پیشنهاد کنید تا اشتراک سازمانی این پایگاه را برای دسترسی نامحدود همه کاربران به متن مطالب تهیه نمایند!
توجه!
  • حق عضویت دریافتی صرف حمایت از نشریات عضو و نگهداری، تکمیل و توسعه مگیران می‌شود.
  • پرداخت حق اشتراک و دانلود مقالات اجازه بازنشر آن در سایر رسانه‌های چاپی و دیجیتال را به کاربر نمی‌دهد.
In order to view content subscription is required

Personal subscription
Subscribe magiran.com for 70 € euros via PayPal and download 70 articles during a year.
Organization subscription
Please contact us to subscribe your university or library for unlimited access!