Design of advanced siRNA therapeutics for the treatment of COVID-19

被引:18
作者
Niktab, Iman [1 ,2 ]
Haghparast, Maryam [1 ]
Beigi, Mohammad-Hossein [1 ,3 ]
Megraw, Timothy L. [4 ]
Kiani, Amirkianoosh [3 ]
Ghaedi, Kamran [1 ]
机构
[1] Univ Isfahan, Fac Biol Sci & Technol, Dept Cell & Mol Biol & Microbiol, Hezar Jerib Ave,Azadi Sq, Esfahan 8174673441, Iran
[2] Shahid Bahonar Univ Kerman, Dept Biol, Fac Sci, Kerman, Iran
[3] Ontario Tech Univ, Fac Engn & Appl Sci, Silicon Hall Micro Nano Mfg Facil, Oshawa, ON, Canada
[4] Florida State Univ, Coll Med, Dept Biomed Sci, West Call St, Tallahassee, FL 32306 USA
基金
加拿大自然科学与工程研究理事会;
关键词
siRNAs; COVID-19; SARS-CoV-2; qRT-PCR; SARS-COV; DISEASE; KNOCKING; PROGRESS;
D O I
10.1016/j.mgene.2021.100910
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
COVID-19 is a newly emerged viral disease that is currently affecting the whole globe. A variety of therapeutic approaches are underway to block the SARS-CoV-2 virus. Among these methods, siRNAs could be a safe and specific option, as they have been tested against other viruses. siRNAs are a class of inhibitor RNAs that act promisingly as mRNA expression blockers and they can be designed to interfere with viral mRNA to block virus replication. In order to do this, we designed and evaluated the efficacy of six highly specific siRNAs, which target essential viral mRNAs with no predicted human genome off-targets. We observed a significant reduction in the copy number viral mRNAs after treatment with the siRNAs, and are expected to inhibit virus replication. We propose siRNAs as a potential co-therapy for acute SARS-CoV-2 infection.
引用
收藏
页数:4
相关论文
共 19 条
[1]   COVID-19 treatment options: a difficult journey between failed attempts and experimental drugs [J].
Bartoli, Alessandra ;
Gabrielli, Filippo ;
Alicandro, Tatiana ;
Nascimbeni, Fabio ;
Andreone, Pietro .
INTERNAL AND EMERGENCY MEDICINE, 2021, 16 (02) :281-308
[2]  
Carter LJ, 2020, PMCA: Permutation -based Maximum Covariance Analysis
[3]   Interfering with disease: a progress report on siRNA-based therapeutics [J].
de Fougerolles, Antonin ;
Vornlocher, Hans-Peter ;
Maraganore, John ;
Lieberman, Judy .
NATURE REVIEWS DRUG DISCOVERY, 2007, 6 (06) :443-453
[4]   The spike protein of SARS-CoV - a target for vaccine and therapeutic development [J].
Du, Lanying ;
He, Yuxian ;
Zhou, Yusen ;
Liu, Shuwen ;
Zheng, Bo-Jian ;
Jiang, Shibo .
NATURE REVIEWS MICROBIOLOGY, 2009, 7 (03) :226-236
[5]   Knocking down disease with siRNAs [J].
Dykxhoorn, Derek M. ;
Lieberman, Judy .
CELL, 2006, 126 (02) :231-235
[6]   An interferon-γ-related cytokine storm in SARS patients [J].
Huang, KJ ;
Su, IJ ;
Theron, M ;
Wu, YC ;
Lai, SK ;
Liu, CC ;
Lei, HY .
JOURNAL OF MEDICAL VIROLOGY, 2005, 75 (02) :185-194
[7]   The Architecture of SARS-CoV-2 Transcriptome [J].
Kim, Dongwan ;
Lee, Joo-Yeon ;
Yang, Jeong-Sun ;
Kim, Jun Won ;
Kim, V. Narry ;
Chang, Hyeshik .
CELL, 2020, 181 (04) :914-+
[8]   T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus [J].
Kondratowicz, Andrew S. ;
Lennemann, Nicholas J. ;
Sinn, Patrick L. ;
Davey, Robert A. ;
Hunt, Catherine L. ;
Moller-Tank, Sven ;
Meyerholz, David K. ;
Rennert, Paul ;
Mullins, Robert F. ;
Brindley, Melinda ;
Sandersfeld, Lindsay M. ;
Quinn, Kathrina ;
Weller, Melodie ;
McCray, Paul B., Jr. ;
Chiorini, John ;
Maury, Wendy .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (20) :8426-8431
[9]   Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in rhesus macaque [J].
Li, BJ ;
Tang, QQ ;
Cheng, D ;
Qin, C ;
Xie, FY ;
Wei, Q ;
Xu, J ;
Liu, YJ ;
Zheng, BJ ;
Woodle, MC ;
Zhong, NS ;
Lu, PY .
NATURE MEDICINE, 2005, 11 (09) :944-951
[10]  
Rychlik Wojciech, 2007, V402, P35