Doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts

Chong Teoh, Teow and Al-Harbi, Sawsam J. and Abdulrahman, Ammar Yasir and Rothan, Hussin A. (2021) Doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts. Molecules, 26 (14). ISSN 1420-3049, DOI

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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 degrees C) and human temperature with a high fever during virus infection (40 degrees C). Interestingly, doxycycline showed a higher inhibitory effect at 40 degrees C (IC50 = 5.3 mu M) compared to 37 degrees C (9.9 mu M). The virus replication was considerably reduced by increasing the concentration of doxycycline. An approximately 50% reduction in virus replication was observed at 20 mu M of doxycycline. Treatment with 20 mu M of doxycycline reduced the cytopathic effects (CPE), and the 40 mu M 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.

Item Type: Article
Uncontrolled Keywords: Doxycycline; Zika virus; Flavivirus; NS2B-NS3 viral protease; Human skin fibroblast
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > R Medicine (General)
Divisions: Faculty of Science > Institute of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 28 Feb 2022 06:45
Last Modified: 28 Feb 2022 06:45

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