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.

Ex Input:
The coronavirus (CoV) responsible for severe acute respiratory syndrome (SARS), SARS-CoV, encodes two large polyproteins (pp1a and pp1ab) that are processed by two viral proteases to yield mature non-structural proteins (nsps). Many of these nsps have essential roles in viral replication, but several have no assigned function and possess amino acid sequences that are unique to the CoV family. One such protein is SARS-CoV nsp1, which is processed from the N-terminus of both pp1a and pp1ab. The mature SARS-CoV protein is present in cells several hours post-infection and co-localizes to the viral replication complex, but its function in the viral life cycle remains unknown. Furthermore, nsp1 sequences are highly divergent across the CoV family, and it has been suggested that this is due to nsp1 possessing a function speciWc to viral interactions with its host cell or acting as a host speciWc virulence factor. In order to initiate structural and biophysical studies of SARS-CoV nsp1, a recombinant expression system and a puriWcation protocol have been developed, yielding milligram quantities of highly puriWed SARS-CoV nsp1. The puriWed protein was characterized using circular dichroism, size exclusion chromatography, and multi-angle light scattering.

Ex Output:
Expression, puriWcation and characterization of recombinant severe acute respiratory syndrome coronavirus non-structural protein 1


Ex Input:
Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract Orthoquin TM is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or premature release of viral genomes, as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that the broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins. facilitate attachment and entry into host cells. While HSV-1 and HSV-2 are similar, they share onlỹ 55% nucleotide identity. Lytic HSV infection of a cell begins with initial attachment to negatively charged cell surface heparan sulfate and chondroitin sulfate glycosaminoglycans, followed by stable attachment of viral glycoproteins to cell surface receptors and fusion of the viral envelope to the plasma membrane or internal membranes [2] . Fusion of viral and host membranes enables delivery of the viral nucleocapsid and tegument proteins to the cytoplasm. After the HSV nucleocapsid arrives at the nucleus and delivers the viral genome, HSV genes are expressed in an ordered temporal cascade. Viral egress requires primary envelopment of the genome-containing capsid at the inner nuclear membrane, fusion with the outer nuclear membrane and final envelopment at the trans-Golgi network. Mature virions then exit through the cellular secretory system. All stages of the HSV replication cycle offer potential targets for direct-acting antiviral (DAA) therapy. However, DAAs can be undermined by the emergence of drug resistant mutant viruses. Anti-HSV DAAs acyclovir and foscarnet offer examples of the hazards of drug resistance. These drugs interrupt HSV genome replication by different mechanisms of action. Acyclovir is a nucleoside analogue prodrug that selectively targets HSV infected cells through the action of the HSV thymidine kinase (TK) enzyme, which efficiently phosphorylates acyclovir and facilitates incorporation into nascent viral DNA genomes by the HSV DNA polymerase enzyme; incorporation of acyclovir into viral DNA terminates genome replication [3] . By contrast, the pyrophosphate analogue foscarnet blocks viral genome replication by directly inhibiting HSV DNA polymerase activity [4] . Though resistance to acyclovir occurs at a low prevalence (≤1%) in immunocompetent patients [5], immunocompromised patients experience much higher rates (4-10%) [6] . Unsurprisingly, resistance to acyclovir, and its derivatives, and to foscarnet, has been mapped to mutations in the viral thymidine kinase and the DNA polymerase catalytic subunit, respectively [7] . Currently, Abreva (n-docosanol) is the only over-the-counter topical antiviral for herpes labialis. Abreva is incorporated into the cellular plasma membrane and prevents fusion steps essential for HSV-1 entry into epithelial cells [8] . However, it must be applied repeatedly throughout the day due to rapid plasma membrane turnover and the subsequent loss of n-docosanol [9] . This host-targeted antiviral mechanism prevents development of viral resistance, but Abreva is only approved for perioral lesions, so there is a still a gap in treatment for lesions in other areas of the body. Like Abreva, there is potential for more broadly-acting antiviral drugs that exploit the physical structure of the HSV virion and block early stages of infection, such as attachment and penetration. In this study, we explored the potential of the plant-derived photosensitizing agent Orthoquin TM to mediate photodynamic inactivation (PDI) [10] of virions. The clinical utility of Orthoquin PDI of oral biofilms is an area of active investigation and there is clear potential for wider range of clinical applications. The basis of PDI is the photodynamic effect, which has been exploited in photodynamic therapy (PDT) [11, 12] for treatment of cancers [13] and age-related macular degeneration [14] . In PDT, photosensitizer compounds when exposed to visible light react with oxygen to generate reactive oxygen species (ROS) that include singlet oxygen [15] . ROS damage proteins, nucleic acids and lipids, which can lead to cell death. Some of the most well-known photosensitizing molecules for PDT are based on a tetrapyrrolic core and are found in naturally occurring pigments, such as heme, chlorophyll, and bacteriochlorophyll [16] . The accepted phototoxic mechanism for these types of photosensitizers involves the formation of an excited triplet state upon light absorption that can participate in electron (Type 1) or energy (Type 2) transfer processes. Type 1 electron transfer reactions typically lead to the formation of radical species like superoxide or hydroxyl radicals, whereas Type 2 energy transfer produces cytotoxic singlet oxygen. It is possible for a photosensitizer to initiate both Type 1 and 2 photoprocesses simultaneously, depending on the specific chemistry of the photosensitizing agent and its environment [16] . Due to the high reactivities and short lifetimes of oxidizing molecules, it is expected that only viral structures in close proximity to activated photosensitizing compounds will be affected.

Ex Output:
Photodynamic Inactivation of Herpes Simplex Viruses


Ex Input:
Human immunodeficiency virus type 1 (HIV-1) Tat plays an important role in HIV-associated neuropathogenesis; the underlying mechanisms are still evolving. We have recently shown that HIV-1 Tat induces expression of glial fibrillary acidic protein (GFAP), a characteristic of HIV-1 infection of the central nervous system (CNS). We have also shown that the Tat-induced GFAP expression in astrocytes is regulated by p300, and that deletion of the early growth response 1 (Egr-1) cis-transacting element within the p300 promoter abolishes Tat-induced GFAP expression. In this study, we further examined the relationship between Tat and Egr-1 in astrocytes. We found increased Egr-1 protein expression in Tat-expressing human astrocytoma cells and mouse primary astrocytes. Using the Egr-1 promoter-driven firefly luciferase reporter gene assay and the sitedirected mutagenesis, we demonstrated that Tat increased Egr-1 expression by transactivating the Egr-1 promoter and involving specific serum response elements (SRE) within the promoter. Consistent with these data, we showed that Tat transactivation of the Egr-1 promoter was abrogated when astrocytes were cultured in serum-reduced media. Taken together, these results reveal that Tat directly transactivates Egr-1 expression and suggest that Tat interaction with Egr-1 is probably one of the very upstream molecular events that initiate Tat-induced astrocyte dysfunction and subsequent Tat neurotoxicity.

Ex Output:

Activation of Egr-1 expression in astrocytes by HIV-1 Tat: new insights into astrocyte-mediated Tat neurotoxicity