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RdRp inhibitors and COVID-19: Is molnupiravir a good option? - 16/01/22

Doi : 10.1016/j.biopha.2021.112517 
Seyed Mohammad Reza Hashemian a, Mohammad Hossein Pourhanifeh b, Michael R. Hamblin c, Mohammad Karim Shahrzad d, , Hamed Mirzaei e, f,
a Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran 
b School of Medicine, Kashan University of Medical Sciences, Kashan, Iran 
c Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa 
d Department of Internal Medicine and Endocrinology,‎ ShohadaeTajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 
e Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran 
f Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, IR, Iran 

Corresponding author.⁎⁎Corresponding author at: Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, IR, Iran.Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical SciencesKashanIRIran

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Abstract

Rapid changes in the viral genome allow viruses to evade threats posed by the host immune response or antiviral drugs, and can lead to viral persistence in the host cells. RNA-dependent RNA polymerase (RdRp) is an essential enzyme in RNA viruses, which is involved in RNA synthesis through the formation of phosphodiester bonds. Therefore, in RNA viral infections such as SARS-CoV-2, RdRp could be a crucial therapeutic target. The present review discusses the promising application of RdRp inhibitors, previously approved or currently being tested in human clinical trials, in the treatment of RNA virus infections. Nucleoside inhibitors (NIs) bind to the active site of RdRp, while nonnucleoside inhibitors (NNIs) bind to allosteric sites. Given the absence of highly effective drugs for the treatment of COVID-19, the discovery of an efficient treatment for this pandemic is an urgent concern for researchers around the world. We review the evidence for molnupiravir (MK-4482, EIDD-2801), an antiviral drug originally designed for Alphavirus infections, as a potential preventive and therapeutic agent for the management of COVID-19. At the beginning of this pandemic, molnupiravir was in preclinical development for seasonal influenza. When COVID-19 spread dramatically, the timeline for development was accelerated to focus on the treatment of this pandemic. Real time consultation with regulators took place to expedite this program. We summarize the therapeutic potential of RdRp inhibitors, and highlight molnupiravir as a new small molecule drug for COVID-19 treatment.

El texto completo de este artículo está disponible en PDF.

Keywords : SARS-CoV-2, Small molecule drug, RdRp inhibitors, Molnupiravir, Clinical trials


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© 2021  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 146

Artículo 112517- février 2022 Regresar al número
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