In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
Example: The severe acute respiratory syndrome (SARS) epidemic originating from China in 2002 was caused by a previously uncharacterized coronavirus that could be identified by specific RT-PCR amplification. Efforts to control future SARS outbreaks depend on the accurate and early identification of SARS-CoV infected patients. A real-time fluorogenic RT-PCR assay based on the 3 -noncoding region (3 -NCR) of SARS-CoV genome was developed as a quantitative SARS diagnostic tool. The ideal amplification efficiency of a sensitive SARS-CoV RT-PCR assay should yield an E value (PCR product concentration increase per amplification cycle) equal to 2.0. It was demonstrated that the 3 -NCR SARS-CoV based RT-PCR reactions could be formulated to reach excellent E values of 1.81, or 91% amplification efficacy. The SARS-CoV cDNA preparations derived from viral RNA extract and the cloned recombinant plasmid both exhibit the identical amplification characteristics, i.e. amplification efficacy using the same PCR formulation developed in this study. The viral genomic copy (or genomic equivalences, GE) per infectious unit (GE/pfu) of SARS-CoV used in this study was also established to be approximate 1200-1600:1. The assay's detection sensitivity could reach 0.005 pfu or 6-8 GE per assay. It was preliminarily demonstrated that the assay could efficiently detect SARS-CoV from clinical specimens of SARS probable and suspected patients identified in Taiwan. The 3 -NCR based SARS-CoV assay demonstrated 100% diagnostic specificity testing samples of patients with acute respiratory disease from a non-SARS epidemic region.
Example solution: Development and evaluation of an efficient 3 -noncoding region-based SARS coronavirus (SARS-CoV) RT-PCR assay for detection of SARS-CoV
Example explanation: It's a correct title because the paragraph described the development of 3 -noncoding region of SARS-CoV genome and assay efficiently detecting SARS-CoV from clinical specimens.

Problem: word count: 359 20 Text word count: 4423 21 22 All rights reserved. No reuse allowed without permission. ABSTRACT 23 The 3-to-5 exoribonuclease in coronavirus (CoV) nonstructural protein 14 (nsp14-ExoN) 24 mediates RNA proofreading during genome replication. ExoN catalytic residues are arranged in 25 three motifs: I (DE), II (E), III (D). Alanine substitution of the motif I residues (AA-E-D, four 26 nucleotide substitutions) in murine hepatitis virus (MHV) and SARS-CoV yields viable mutants 27 with impaired replication and fitness, increased mutation rates, and attenuated virulence in vivo. 28 Despite these impairments, MHV-and SARS-CoV ExoN motif I AA mutants (ExoN-AA) have 29 not reverted at motif I in diverse in vitro and in vivo environments, suggesting that profound 30 fitness barriers prevent motif I reversion. To test this hypothesis, we engineered MHV-ExoN-AA 31 with 1, 2 or 3 nucleotide mutations along genetic pathways to AA-to-DE reversion. We show 32 that engineered intermediate revertants were viable but had no increased replication or 33 competitive fitness compared to MHV-ExoN-AA. In contrast, a low passage (P10) MHV-ExoN-34 AA showed increased replication and competitive fitness without reversion of ExoN-AA. 35 Finally, engineered reversion of ExoN-AA to ExoN-DE in the presence of ExoN-AA passage-36 adaptive mutations resulted in significant fitness loss. These results demonstrate that while 37 reversion is possible, at least one alternative adaptive pathway is more rapidly advantageous than 38 intermediate revertants and may alter the genetic background to render reversion detrimental to 39 fitness. Our results provide an evolutionary rationale for lack of ExoN-AA reversion, illuminate 40 potential multi-protein replicase interactions and coevolution, and support future studies aimed at 41 stabilizing attenuated CoV ExoN-AA mutants. 42 43 All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/618249 doi: bioRxiv preprint Coronaviruses encode an exoribonuclease (ExoN) that is important for viral replication, fitness, 45 and virulence, yet coronaviruses with a defective ExoN (ExoN-AA) have not reverted under 46 diverse experimental conditions. In this study, we identify multiple impediments to MHV-ExoN-47 AA reversion. We show that ExoN-AA reversion is possible but evolutionarily unfavorable. 48 Instead, compensatory mutations outside of ExoN-AA motif I are more accessible and beneficial 49 than partial reversion. We also show that coevolution between replicase proteins over long-term 50 passage partially compensates for ExoN-AA motif I but renders the virus inhospitable to a 51 reverted ExoN. Our results reveal the evolutionary basis for the genetic stability of ExoN-52 inactivating mutations, illuminate complex functional and evolutionary relationships between 53 coronavirus replicase proteins, and identify potential mechanisms for stabilization of ExoN-AA 54 coronavirus mutants. 55 All rights reserved. No reuse allowed without permission.
Solution: Fitness barriers limit reversion of a proofreading-deficient coronavirus 1 2