Potency of a small molecule that targets the molluscum contagiosum virus processivity factor increases when conjugated to a tripeptide

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2024-05-03 DOI:10.1016/j.antiviral.2024.105899

Hancheng Guan , Manunya Nuth , Richard W. Scott , Michael H. Parker , Eric D. Strobel , Allen B. Reitz , John L. Kulp III , Robert P. Ricciardi

引用次数: 0

Abstract

We recently developed compound FC-7269 for targeting the Molluscum contagiosum virus processivity factor (mD4) and demonstrated its ability to inhibit viral processive DNA synthesis in vitro and cellular infection of an mD4-dependent virus (Antiviral Res 211, 2023,105520). However, despite a thorough medicinal chemistry campaign we were unable to generate a potent second analog as a requisite for drug development. We overcame this impasse, by conjugating a short hydrophobic trivaline peptide to FC-7269 to produce FC-TriVal-7269 which significantly increased antiviral potency and reduced cellular toxicity.

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针对软疣病毒加工因子的小分子与三肽共轭后效力增强

我们最近开发了针对传染性软疣病毒过程因子（mD4）的化合物 FC-7269，并证明了其在体外抑制病毒过程 DNA 合成和抑制依赖 mD4 病毒的细胞感染的能力（Antiviral Res 211, 2023,105520）。然而，尽管我们进行了全面的药物化学研究，但仍无法生成药物开发所需的强效第二类似物。我们克服了这一僵局，在 FC-7269 上连接了一个短的疏水三价肽，生成了 FC-TriVal-7269，显著提高了抗病毒效力并降低了细胞毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.