دورية أكاديمية
أعرض في EDS

Doxycycline Interferes with Zika Virus Serine Protease and Inhibits Virus Replication in Human Skin Fibroblasts.

التفاصيل البيبلوغرافية
العنوان: Doxycycline Interferes with Zika Virus Serine Protease and Inhibits Virus Replication in Human Skin Fibroblasts.
المؤلفون: Chong Teoh T; Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, Kuala Lumpur 50603, Malaysia., J Al-Harbi S; Department of Anatomy, College of Medicine, University of Babylon, Babylon, Iraq., Abdulrahman AY; Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia., Rothan HA; Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
المصدر: Molecules (Basel, Switzerland) [Molecules] 2021 Jul 16; Vol. 26 (14). Date of Electronic Publication: 2021 Jul 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, c1995-
مواضيع طبية MeSH: Doxycycline/*pharmacology , Fibroblasts/*metabolism , Skin/*metabolism , Viral Nonstructural Proteins/*antagonists & inhibitors , Viral Proteins/*antagonists & inhibitors , Virus Replication/*drug effects , Zika Virus/*physiology, Animals ; Chlorocebus aethiops ; Doxycycline/chemistry ; Fibroblasts/virology ; Humans ; Serine Endopeptidases/chemistry ; Serine Endopeptidases/metabolism ; Skin/virology ; Vero Cells ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/metabolism ; Viral Proteins/chemistry ; Viral Proteins/metabolism ; Zika Virus/chemistry
مستخلص: Zika virus (ZIKV) represents a re-emerging threat to global health due to its association with congenital birth defects. ZIKV NS2B-NS3 protease is crucial for virus replication by cleaving viral polyprotein at various junctions to release viral proteins and cause cytotoxic effects in ZIKV-infected cells. This study characterized the inhibitory effects of doxycycline against ZIKV NS2B-NS3 protease and viral replication in human skin cells. The in silico data showed that doxycycline binds to the active site of ZIKV protease at a low docking energy (-7.8 Kcal/mol) via four hydrogen bonds with the protease residues TYR1130, SER1135, GLY1151, and ASP83. Doxycycline efficiently inhibited viral NS2B-NS3 protease at average human temperature (37 °C) and human temperature with a high fever during virus infection (40 °C). Interestingly, doxycycline showed a higher inhibitory effect at 40 °C (IC50 = 5.3 µM) compared to 37 °C (9.9 µM). The virus replication was considerably reduced by increasing the concentration of doxycycline. An approximately 50% reduction in virus replication was observed at 20 µM of doxycycline. Treatment with 20 µM of doxycycline reduced the cytopathic effects (CPE), and the 40 µM of doxycycline almost eliminated the CPE of human skin cells. This study showed that doxycycline binds to the ZIKV protease and inhibits its catalytic activity at a low micro-molecular concentration range. Treatment of human skin fibroblast with doxycycline eliminated ZIKV infection and protected the cells against the cytopathic effects of the infection.
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معلومات مُعتمدة: TR001B-2014B Institut Pengurusan dan Pemantauan Penyelidikan, Universiti Malaya
فهرسة مساهمة: Keywords: NS2B-NS3 viral protease; doxycycline; flavivirus; human skin fibroblast; zika virus
المشرفين على المادة: 0 (NS2B protein, flavivirus)
0 (Viral Nonstructural Proteins)
0 (Viral Proteins)
EC 3.4.- (NS3 protein, zika virus)
EC 3.4.21.- (Serine Endopeptidases)
N12000U13O (Doxycycline)
تواريخ الأحداث: Date Created: 20210724 Date Completed: 20210915 Latest Revision: 20210915
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8306286
DOI: 10.3390/molecules26144321
PMID: 34299596
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-3049
DOI:10.3390/molecules26144321