发布时间:2017-09-03 15:13:00
The global SARS (severe acute respiratory syndrome) and MERS (Middle Eastrespiratory syndrome coronavirus) epidemics caused by corona virus broke out and remain a threat to public health; however, effective vaccine or drug against CoVs remains unavailable. CoV helicase is one of the most conserved evolutionary nonstructural proteins (nsps), and one of core proteins that constitute viral transcription/replication transcription complex, thus making it an important target for drug development. Nsp13 belongs to SF1 helicase super family and has several enzymatic activities, including hydrolysis of NTPs and dNTPs, unwinding of DNA and RNA duplexes with 5’-3’directionality and the RNA5’-triphosphatase activity. Through resolution of crystal structure, the researchers have found that, MERS-CoV nsp13 has multiple domains, including an N-terminal Cys/His rich domain (CH) with three zinc atoms, a beta-barrel domain and a C-terminal SF1 helicase core with two RecA-like subdomains. Compared with existing protein structure databases, we have found that, on one hand, the overall domain organization structure of nsp13 is similar to that of EAV nsp10, indicating that the structure of helicase is highly conserved in nidovirales; on the other hand, the structure of all structure domains in nsp13 is more similar to the structure domain corresponding to the Upf1 helicase in eucaryotic organism. That is to say, if Upf1 is considered as an advanced version in the evolution of Upf1-like helicase, EAV nsp10 can be seen as simple version, while CoV nsp13 is between Upf1 and EAV nsp10 inevolution. It is worth noting that, the N-terminal CH structure domain of CoV nsp13 highly resembles CH of Upf1. Upf1 takes part in nonsense-mediated mRNA decay (NMD), and NMD can recognize and degrade exogenous RNA (including viral RNA), and cause the host defense mechanism. Therefore, nsp13 may take part in quality control of viral RNAs synthesis, and can support the efficient replication of its exceptional RNA large genome; nsp13 may also use the CH structure domain that is highly similar to Upf1 to disturb the host NMD, thereby resisting the NMD-mediated anti-viral mechanism. The assumptions need further experimental evidences.
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