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.

Q: Background: SARS coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and extensive investigations indicated that it originated from an animal source (probably bats) and was recently introduced into the human population via wildlife animals from wet markets in southern China. Previous studies revealed that the spike (S) protein of SARS had experienced adaptive evolution, but whether other functional proteins of SARS have undergone adaptive evolution is not known. We employed several methods to investigate selective pressure among different SARS-CoV groups representing different epidemic periods and hosts. Our results suggest that most functional proteins of SARS-CoV have experienced a stepwise adaptive evolutionary pathway. Similar to previous studies, the spike protein underwent strong positive selection in the early and middle phases, and became stabilized in the late phase. In addition, the replicase experienced positive selection only in human patients, whereas assembly proteins experienced positive selection mainly in the middle and late phases. No positive selection was found in any proteins of bat SARS-like-CoV. Furthermore, specific amino acid sites that may be the targets of positive selection in each group are identified. This extensive evolutionary analysis revealed the stepwise evolution of different functional proteins of SARS-CoVs at different epidemic stages and different hosts. These results support the hypothesis that SARS-CoV originated from bats and that the spill over into civets and humans were more recent events.

A: Differential stepwise evolution of SARS coronavirus functional proteins in different host species
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Q: The high mutation rate of the human immunodeficiency virus type 1 (HIV-1) virus is a major problem since it evades the function of antibodies and chemical inhibitors. Here, we demonstrate a viral detection strategy based on synthetic biology principles to detect a specific viral function rather than a particular viral protein. The resistance caused by mutations can be circumvented since the mutations that cause the loss of function also incapacitate the virus. Many pathogens encode proteases that are essential for their replication and that have a defined substrate specificity. A genetically encoded sensor composed of a fused membrane anchor, viral protease target site, and an orthogonal transcriptional activator was engineered into a human cell line. The HIV-1 protease released the transcriptional activator from the membrane, thereby inducing transcription of the selected genes. The device was still strongly activated by clinically relevant protease mutants that are resistant to protease inhibitors. In the future, a similar principle could be applied to detect also other pathogens and functions.

A: Function-Based Mutation-Resistant Synthetic Signaling Device Activated by HIV-1 Proteolysis
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Q: Extracts of Anthemis hyalina (Ah), Nigella sativa (Ns) and peels of Citrus sinensis (Cs) have been used as folk medicine to fight antimicrobial diseases. To evaluate the effect of extracts of Ah, Ns and Cs on the replication of coronavirus (CoV) and on the expression of TRP genes during coronavirus infection, HeLa-CEACAM1a (HeLa-epithelial carcinoembryonic antigen-related cell adhesion molecule 1a) cells were inoculated with MHV-A59 (mouse hepatitis virus-A59) at moi of 30. 1/50 dilution of the extracts was found to be the safe active dose. ELISA kits were used to detect the human IL-8 levels. Total RNA was isolated from the infected cells and cDNA was synthesized. Fluidigm Dynamic Array nanofluidic chip 96.96 was used to analyze the mRNA expression of 21 TRP genes and two control genes. Data was analyzed using the BioMark digital array software. Determinations of relative gene expression values were carried out by using the 2 -DDCt method (normalized threshold cycle (Ct) value of sample minus normalized Ct value of control). TCID 50 / ml (tissue culture infectious dose that will produce cytopathic effect in 50 % of the inoculated tissue culture cells) was found for treatments to determine the viral loads. The inflammatory cytokine IL-8 level was found to increase for both 24 and 48 h time points following Ns extract treatment. TRPA1, TRPC4, TRPM6, TRPM7, TRPM8 and TRPV4 were the genes which expression levels changed significantly after Ah, Ns or Cs extract treatments. The virus load decreased when any of the Ah, Ns or Cs extracts was added to the CoV infected cells with Ah extract treatment leading to undetectable virus load for both 6 and 8hpi. Although all the extract treatments had an effect on IL-8 secretion, TRP gene expression and virus load after CoV infection, it was the Ah extract treatment that showed the biggest difference in virus load. Therefore Ah extract is the best candidate in our hands that contains potential treatment molecule(s).

A:
The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family
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