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Pharmacological Therapeutics Targeting RNA-Dependent RNA Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-19.
Huang, Jiansheng; Song, Wenliang; Huang, Hui; Sun, Quancai.
  • Huang J; Department of Medicine, Vanderbilt University Medical Center, 318 Preston Research Building, 2200 Pierce Avenue, Nashville, TN 37232, USA.
  • Song W; School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
  • Huang H; Department of Medicine, Vanderbilt University Medical Center, 318 Preston Research Building, 2200 Pierce Avenue, Nashville, TN 37232, USA.
  • Sun Q; Center of Structural Biology, Vanderbilt University, 2200 Pierce Avenue, Nashville, TN 37232, USA.
J Clin Med ; 9(4)2020 Apr 15.
Article in English | MEDLINE | ID: covidwho-60425
ABSTRACT
An outbreak of novel coronavirus-related pneumonia COVID-19, that was identified in December 2019, has expanded rapidly, with cases now confirmed in more than 211 countries or areas. This constant transmission of a novel coronavirus and its ability to spread from human to human have prompted scientists to develop new approaches for treatment of COVID-19. A recent study has shown that remdesivir and chloroquine effectively inhibit the replication and infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCov) in vitro. In the United States, one case of COVID-19 was successfully treated with compassionate use of remdesivir in January of 2020. In addition, a clinically proven protease inhibitor, camostat mesylate, has been demonstrated to inhibit Calu-3 infection with SARS-CoV-2 and prevent SARS-2-spike protein (S protein)-mediated entry into primary human lung cells. Here, we systemically discuss the pharmacological therapeutics targeting RNA-dependent RNA polymerase (RdRp), proteinase and S protein for treatment of SARS-CoV-2 infection. This review should shed light on the fundamental rationale behind inhibition of SARS-CoV-2 enzymes RdRp as new therapeutic approaches for management of patients with COVID-19. In addition, we will discuss the viability and challenges in targeting RdRp and proteinase, and application of natural product quinoline and its analog chloroquine for treatment of coronavirus infection. Finally, determining the structural-functional relationships of the S protein of SARS-CoV-2 will provide new insights into inhibition of interactions between S protein and angiotensin-converting enzyme 2 (ACE2) and enable us to develop novel therapeutic approaches for novel coronavirus SARS-CoV-2.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Year: 2020 Document Type: Article Affiliation country: JCM9041131

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Year: 2020 Document Type: Article Affiliation country: JCM9041131