Synthesis of Novel Test Compounds for Antiviral Chemotherapy of Severe Acute Respiratory Syndrome (SARS)

Kesel, Andreas J.

doi:10.2174/0929867054637644

Cited by 30 publications

(17 citation statements)

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“…In fact, after the outbreak of SARS, many groups dedicated themselves to finding anti-coronavirus agents, including some natural compounds that exist in traditional Chinese herbal medicines [4][5][6][7][8][9][10][11][12]. The coronavirus encodes more than one dozen proteins, some of which are essential to viral entry and replication.…”

Section: Introductionmentioning

confidence: 99%

In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

Zhang¹,

Zhang³

et al. 2020

Journal of Integrative Medicine

424

395

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a b s t r a c tObjective: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia. Methods: There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction. In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb. Results: Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response. Conclusion: Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.

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Section: Introductionmentioning

confidence: 99%

In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

Zhang¹,

Zhang³

et al. 2020

Journal of Integrative Medicine

424

395

View full text Add to dashboard Cite

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“…Several compound families were found to target the ATPase of nsp13, and thus also its helicase activity. These include naturally occurring flavonoids (Yu et al, 2012), chromones (Kim et al, 2011), and bananins (Kesel, 2005;Tanner et al, 2005), all exhibiting in vitro IC 50 values in the low-micromolar range. Other compounds appear to target the helicase of nsp13 activity more specifically, like the triazole SSYA10-001, which was found to inhibit the replication of multiple beta-CoVs (SARS-CoV, MERS-CoV, and MHV) in cell culture-based infection models (Adedeji et al, 2012b(Adedeji et al, , 2014.…”

Section: The Coronavirus Helicase As Drug Targetmentioning

confidence: 99%

The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing

Snijder

Decroly

Ziebuhr

2016

Advances in Virus Research

534

620

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Coronaviruses are animal and human pathogens that can cause lethal zoonotic infections like SARS and MERS. They have polycistronic plus-stranded RNA genomes and belong to the order Nidovirales, a diverse group of viruses for which common ancestry was inferred from the common principles underlying their genome organization and expression, and from the conservation of an array of core replicase domains, including key RNA-synthesizing enzymes. Coronavirus genomes (~26-32 kilobases) are the largest RNA genomes known to date and their expansion was likely enabled by acquiring enzyme functions that counter the commonly high error frequency of viral RNA polymerases. The primary functions that direct coronavirus RNA synthesis and processing reside in nonstructural protein (nsp) 7 to nsp16, which are cleavage products of two large replicase polyproteins translated from the coronavirus genome. Significant progress has now been made regarding their structural and functional characterization, stimulated by technical advances like improved methods for bioinformatics and structural biology, in vitro enzyme characterization, and site-directed mutagenesis of coronavirus genomes. Coronavirus replicase functions include more or less universal activities of plus-stranded RNA viruses, like an RNA polymerase (nsp12) and helicase (nsp13), but also a number of rare or even unique domains involved in mRNA capping (nsp14, nsp16) and fidelity control (nsp14). Several smaller subunits (nsp7-nsp10) act as crucial cofactors of these enzymes and contribute to the emerging "nsp interactome." Understanding the structure, function, and interactions of the RNA-synthesizing machinery of coronaviruses will be key to rationalizing their evolutionary success and the development of improved control strategies.

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“…Helicase has also been a focal point for the development of antiviral chemotherapy of the coronavirus associated with severe acute respiratory syndrome (SARS) in humans. Although several experimental compounds with nucleic acid binding activity showing effective inhibition of SARS-CoV helicase were reported in 2005, there have been no reports of any further development since that time (Kesel 2005). It remains to be seen whether the SARS-CoV compounds will be developed further, especially since no new infections have been observed in recent years.…”

Section: Helicase Inhibitorsmentioning

confidence: 99%

Other Inhibitors of Viral Enzymes and Functions

Zimmermann

Hewlett²,

Rübsamen‐Waigmann

2009

Antiviral Strategies

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Until the end of the 1970s, the mainstays of antiviral chemotherapy were nucleoside analogues that targeted virus polymerase, in particular, the herpesvirus DNA polymerase. The scourge of HIV triggered an unprecedented commitment to identify novel antivirals, and these efforts transformed antiviral therapy into the modern, sophisticated treatment form described in this book, with targets such as the reverse transcriptase and the protease as well as the entry of the human immunodeficiency virus. As the regulation of human pathogenic virus growth cycles became more understandable, the realisation grew that these pathogens had more than one Achilles heel that might be suitable targets for small molecules with antiviral activity. This chapter addresses those "other" targets as well as other approaches to the tried and tested polymerase inhibitors, the so-called non-nucleoside inhibitors of reverse transcriptase.

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Synthesis of Novel Test Compounds for Antiviral Chemotherapy of Severe Acute Respiratory Syndrome (SARS)

Cited by 30 publications

References 0 publications

In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing

Other Inhibitors of Viral Enzymes and Functions

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