TY - JOUR
T1 - Crosstalk between endoplasmic reticulum stress and anti-viral activities
T2 - A novel therapeutic target for COVID-19
AU - Banerjee, Aditi
AU - Czinn, Steven J.
AU - Reiter, Russel J.
AU - Blanchard, Thomas G.
N1 - Funding Information:
We wish to thank the Department of Pediatrics at the University of Maryland School of Medicine for support. We acknowledge Vivekjyoti Banerjee for creating the corona virus graphic using Blender software. A.B wrote the original draft, T.G.B. S. J. C. and R. J. R reviewed, and edited the manuscript. The authors declare that they have no competing interests.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/8/15
Y1 - 2020/8/15
N2 - The outbreak of COVID-19 caused by 2019–nCov/SARS-CoV-2 has become a pandemic with an urgent need for understanding the mechanisms and identifying a treatment. Viral infections including SARS-CoV are associated with increased levels of reactive oxygen species, disturbances of Ca++ caused by unfolded protein response (UPR) mediated by endoplasmic reticulum (ER) stress and is due to the exploitation of virus's own protein i.e., viroporins into the host cells. Several clinical trials are on-going including testing Remdesivir (anti-viral), Chloroquine and Hydroxychloroquine derivatives (anti-malarial drugs) etc. Unfortunately, each drug has specific limitations. Herein, we review the viral protein involvement to activate ER stress transducers (IRE-1, PERK, ATF-6) and their downstream signals; and evaluate combination therapies for COVID-19 mediated ER stress alterations. Melatonin is an immunoregulator, anti-pyretic, antioxidant, anti-inflammatory and ER stress modulator during viral infections. It enhances protective mechanisms for respiratory tract disorders. Andrographolide, isolated from Andrographis paniculata, has versatile biological activities including immunomodulation and determining SARS-CoV-2 binding site. Considering the properties of both compounds in terms of anti-inflammatory, antioxidant, anti-pyrogenic, anti-viral and ER stress modulation and computational approaches revealing andrographolide docks with the SARS-CoV2 binding site, we predict that this combination therapy may have potential utility against COVID-19.
AB - The outbreak of COVID-19 caused by 2019–nCov/SARS-CoV-2 has become a pandemic with an urgent need for understanding the mechanisms and identifying a treatment. Viral infections including SARS-CoV are associated with increased levels of reactive oxygen species, disturbances of Ca++ caused by unfolded protein response (UPR) mediated by endoplasmic reticulum (ER) stress and is due to the exploitation of virus's own protein i.e., viroporins into the host cells. Several clinical trials are on-going including testing Remdesivir (anti-viral), Chloroquine and Hydroxychloroquine derivatives (anti-malarial drugs) etc. Unfortunately, each drug has specific limitations. Herein, we review the viral protein involvement to activate ER stress transducers (IRE-1, PERK, ATF-6) and their downstream signals; and evaluate combination therapies for COVID-19 mediated ER stress alterations. Melatonin is an immunoregulator, anti-pyretic, antioxidant, anti-inflammatory and ER stress modulator during viral infections. It enhances protective mechanisms for respiratory tract disorders. Andrographolide, isolated from Andrographis paniculata, has versatile biological activities including immunomodulation and determining SARS-CoV-2 binding site. Considering the properties of both compounds in terms of anti-inflammatory, antioxidant, anti-pyrogenic, anti-viral and ER stress modulation and computational approaches revealing andrographolide docks with the SARS-CoV2 binding site, we predict that this combination therapy may have potential utility against COVID-19.
KW - 2019-nCov/SARS-CoV-2
KW - Andrographolide
KW - COVID-19
KW - Endoplasmic reticulum stress
KW - Melatonin
KW - Unfolded protein response
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U2 - 10.1016/j.lfs.2020.117842
DO - 10.1016/j.lfs.2020.117842
M3 - Review article
C2 - 32454157
AN - SCOPUS:85085353778
VL - 255
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
M1 - 117842
ER -