A Novel Chemical Compound for Inhibition of SARS Coronavirus Helicase
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초록
We have discovered a novel chemical compound, (E)-3-(furan-2-yl)-N-(4-sulfamoylphenyl) acrylamide, that suppresses the enzymatic activities of SARS coronavirus helicase. To determine the inhibitory effect, ATP hydrolysis and double-stranded DNA unwinding assays were performed in the presence of various concentrations of the compound. Through these assays, we obtained IC50 values of 2.09 ± 0.30 μM (ATP hydrolysis) and 13.2 ± 0.9 μM (DNA unwinding), respectively. Moreover, we found that the compound did not have any significant cytotoxicity when 40 μM of it was used. Our results showed that the compound might be useful to be developed as an inhibitor against SARS coronavirus.
Abstract
We have discovered a novel chemical compound, (E)-3-(furan-2-yl)-N-(4-sulfamoylphenyl) acrylamide, that suppresses the enzymatic activities of SARS coronavirus helicase. To determine the inhibitory effect, ATP hydrolysis and double-stranded DNA unwinding assays were performed in the presence of various concentrations of the compound. Through these assays, we obtained IC50 values of 2.09 ± 0.30 μM (ATP hydrolysis) and 13.2 ± 0.9 μM (DNA unwinding), respectively. Moreover, we found that the compound did not have any significant cytotoxicity when 40 μM of it was used. Our results showed that the compound might be useful to be developed as an inhibitor against SARS coronavirus.
참고문헌 (19)
- Marra MA, "The genome sequence of the SARS-associated coronavirus", Science, 300, pp.1399~1404 (2003)
- Rota PA, "Characterization of a novel coronavirus associated with severe acute respiratory syndrome", Science, 300, pp.1394~1399 (2003)
- Lai MM, "The molecular biology of coronaviruses", Adv. Virus Res, 48, pp.1~100 (1997)
- Ziebuhr J, "Virus-encoded proteinases and proteolytic processing in the Nidovirales", J. Gen. Virol, 81, pp.853~879 (2000)
- Ivanov KA, "Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase", J. Virol, 78, pp.5619~5632 (2004)
- Tanner JA, "The severe acute respiratory syndrome (SARS)coronavirus NTPase", helicase belongs to a distinct class of 5’to 3’ viral helicases, 2003, pp.278, 39578~39582
- Anand K, "Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs", Science, 300, pp.1763~1767 (2003)
- Borowski P, "Nucleotide triphosphatase", helicase of hepatitis C virus as a target for antiviral therapy, 2002, pp.55, 397~412
- Holmes KV., "SARS coronavirus: a new challenge for prevention and therapy", J. Clin. Invest, 111, pp.1605~1609 (2003)
- Patel SS, "Mechanisms of helicases", J. Biol. Chem, 281, pp.18265~18268 (2006)
- Patel SS, "Structure and function of hexameric helicases", Annu. Rev. Biochem, 69, pp.651~697 (2000)
- Matson SW, "DNA helicases:enzymes with essential roles in all aspects of DNA metabolism", Bioessays, 16, pp.13~22 (1994)
- Lee C, "Aryl diketoacids (ADK) selectively inhibit duplex DNAunwinding activity of SARS coronavirus NTPase", helicase, 2009, pp.19, 1636~1638
- Lee NR, "Cooperative translocation enhances the unwinding of duplex DNA by SARS coronavirus helicase nsP13.", Nucleic Acids Res, 38, pp.7626~7636 (2010)
- Na-Ra Lee, "ATP Hydrolysis Analysis of Severe Acute Respiratory Syndrome (SARS) Coronavirus Helicase", Bulletin of the Korean Chemical Society, 30(8), pp.1724~1728 (2009), 대한화학회
- Lee C, "Investigation of the pharmacophore space of severe acute respiratory syndrome coronavirus (SARS-CoV) NTPase", helicase by dihydroxychromone derivatives, 2009, pp.19, 4538~4541
- Yu MS, "Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13", Bioorg. Med. Chem. Lett, 22, pp.4049~4054 (2012)
- Jang KJ, "Isolation of inhibitory RNA aptamers against severe acute respiratory syndrome (SARS) coronavirus NTPase", helicase, 2008, pp.366, 738~744
- 조진범, "Identification of a Novel Small Molecule Inhibitor Against SARS Coronavirus Helicase", Journal of Microbiology and Biotechnology, 25(12), pp.2007~2010 (2015), 한국미생물·생명공학회[DOI]
