gms | German Medical Science

International Conference on SARS - one year after the (first) outbreak

08. - 11.05.2004, Lübeck

Bioinformatic approaches suggest several putative functional roles of SARS coronavirus RNA-dependent RNA polymerase


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  • presenting/speaker Ralf Moll - Institute of Biochemistry, University of Lübeck, Lübeck, Germany
  • Rolf Hilgenfeld - Institute of Biochemistry, University of Lübeck, Lübeck, Germany

International Conference on SARS - one year after the (first) outbreak. Lübeck, 08.-11.05.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04sarsP11.05

The electronic version of this article is the complete one and can be found online at:

Published: May 26, 2004

© 2004 Moll et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



SARS coronavirus RNA-dependent RNA polymerase (SARS-CoV RdRp) belongs to a subfamily of template-dependent polynucleotide polymerases. Seven sequence motifs (motifs A to G) are conserved among different viral RdRps [1]. They are involved in various functions such as metal-ion binding, binding of the incoming nucleotide, discrimination of deoxyribonucleotides versus ribonucleotides and the polymerization reaction itself. Actually, the active site of the SARS-CoV polymerase is constituted from these motifs. On the basis of structural templates of unrelated viral RdRps, a structural model was recently proposed, which included residues 376 to 932 of the full-length protein [2].

Most remarkable, however, is the N-terminal part of the SARS-CoV RdRp, which comprises about 380 residues. Apparently, this sequence region is unique for coronaviral RdRps, since the corresponding regions of other, unrelated RdRps differ significantly in sequence and length. Moreover, the N-terminal region of coronaviral RdRps is of yet unknown function due to the absence of superfamily-assigning motifs.

Here, the first 300 residues of the SCoV RdRp are proposed to share a common 3D fold with the RNase H of bacteriophage T4, an enzyme that exhibits 5´-3´ exonuclease activity. The active site of the T4 exonuclease is characterized by two Mg2+-ions. Several aspartate residues are arranged in this active site and are conserved in the corresponding SARS-CoV RdRp sequence. However, these aspartates are lacking in HCoV-229E and HCoV-NL63, indicating a possible unique function in the infectious metabolism of SARS coronavirus. Using a threading approach, a structural model is suggested, in which acidic residues may form an acidic cleft capable of binding one magnesium or manganese ion.

Residues 298-310 within the N-terminal part of SCoV RdRp contain a cysteine-rich sequence displaying similarity to the cysteine-rich motif of the HIV-1 transactivator (Tat) protein. In the case of Tat, these cysteines act as ligands for zinc-ions and are involved in a Zn2+-dependent dimerisation reaction [3]. Strikingly, four out of six cysteines are conserved in the SARS-CoV RdRp-N sequence, implying also a possible role in Zn2+-ion binding.

Based on these preliminary investigations, SARS-CoV RdRp is assumed to encompass at least three different functional domains: (I), Mg2+/Mn2+-dependent exonuclease (residues 1-297); (II), a zinc-binding domain (residues 298-375); and (III), the polymerase domain (residues 376-932).


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