TY - JOUR
T1 - Feasibility of known rna polymerase inhibitors as anti-sars-cov-2 drugs
AU - Neogi, Ujjwal
AU - Hill, Kyle J.
AU - Ambikan, Anoop T.
AU - Heng, Xiao
AU - Quinn, Thomas P.
AU - Byrareddy, Siddappa N.
AU - Sönnerborg, Anders
AU - Sarafianos, Stefan G.
AU - Singh, Kamal
N1 - Funding Information:
Funding: K.S. and K.J.H. acknowledge funding from the Bond Life Science Center, University of Missouri, Early Concept Grant. UN acknowledge the funding from the Swedish research Council, Establishment Grant (2017-01330). S.G.S acknowledges U54 AI150472. The study was funded by the Swedish Research Council (2016-01675, AS), Karolinska Institutet, and the Stockholm County Council (ALF 20160074, AS).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/5
Y1 - 2020/5
N2 - Coronaviruses (CoVs) are positive-stranded RNA viruses that infect humans and animals. Infection by CoVs such as HCoV-229E,-NL63,-OC43 and-HKU1 leads to the common cold, short lasting rhinitis, cough, sore throat and fever. However, CoVs such as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and the newest SARS-CoV-2 (the causative agent of COVID-19) lead to severe and deadly diseases with mortality rates ranging between ~1 to 35% depending on factors such as age and pre-existing conditions. Despite continuous global health threats to humans, there are no approved vaccines or drugs targeting human CoVs, and the recent outbreak of COVID-19 emphasizes an urgent need for therapeutic interventions. Using computational and bioinformatics tools, here we present the feasibility of reported broad-spectrum RNA polymerase inhibitors as anti-SARS-CoV-2 drugs targeting its main RNA polymerase, suggesting that investigational and approved nucleoside RNA polymerase inhibitors have potential as anti-SARS-CoV-2 drugs. However, we note that it is also possible for SARS-CoV-2 to evolve and acquire drug resistance mutations against these nucleoside inhibitors.
AB - Coronaviruses (CoVs) are positive-stranded RNA viruses that infect humans and animals. Infection by CoVs such as HCoV-229E,-NL63,-OC43 and-HKU1 leads to the common cold, short lasting rhinitis, cough, sore throat and fever. However, CoVs such as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and the newest SARS-CoV-2 (the causative agent of COVID-19) lead to severe and deadly diseases with mortality rates ranging between ~1 to 35% depending on factors such as age and pre-existing conditions. Despite continuous global health threats to humans, there are no approved vaccines or drugs targeting human CoVs, and the recent outbreak of COVID-19 emphasizes an urgent need for therapeutic interventions. Using computational and bioinformatics tools, here we present the feasibility of reported broad-spectrum RNA polymerase inhibitors as anti-SARS-CoV-2 drugs targeting its main RNA polymerase, suggesting that investigational and approved nucleoside RNA polymerase inhibitors have potential as anti-SARS-CoV-2 drugs. However, we note that it is also possible for SARS-CoV-2 to evolve and acquire drug resistance mutations against these nucleoside inhibitors.
KW - COVID-19
KW - Coronavirus
KW - MERS-CoV
KW - Nsp12
KW - RNA polymerase
KW - SARS-CoV
KW - SARS-CoV-2
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U2 - 10.3390/pathogens9050320
DO - 10.3390/pathogens9050320
M3 - Article
C2 - 32357471
AN - SCOPUS:85084227015
SN - 2076-0817
VL - 9
JO - Pathogens
JF - Pathogens
IS - 5
M1 - 320
ER -