Doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts
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 c...
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my.um.eprints.264192022-02-28T06:45:14Z http://eprints.um.edu.my/26419/ Doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts Chong Teoh, Teow Al-Harbi, Sawsam J. Abdulrahman, Ammar Yasir Rothan, Hussin A. QH301 Biology R Medicine (General) 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. MDPI 2021-07 Article PeerReviewed 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 https://doi.org/10.3390/molecules26144321 <https://doi.org/10.3390/molecules26144321>. 10.3390/molecules26144321 |
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QH301 Biology R Medicine (General) Chong Teoh, Teow Al-Harbi, Sawsam J. Abdulrahman, Ammar Yasir Rothan, Hussin A. Doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts |
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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. |
format |
Article |
author |
Chong Teoh, Teow Al-Harbi, Sawsam J. Abdulrahman, Ammar Yasir Rothan, Hussin A. |
author_facet |
Chong Teoh, Teow Al-Harbi, Sawsam J. Abdulrahman, Ammar Yasir Rothan, Hussin A. |
author_sort |
Chong Teoh, Teow |
title |
Doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts |
title_short |
Doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts |
title_full |
Doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts |
title_fullStr |
Doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts |
title_full_unstemmed |
Doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts |
title_sort |
doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts |
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MDPI |
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2021 |
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http://eprints.um.edu.my/26419/ |
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1735409410249850880 |