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 Input: SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp). Here, using polymerase extension experiments, we have demonstrated that the active triphosphate form of Sofosbuvir (a key component of the FDA approved hepatitis C drug EPCLUSA), is incorporated by SARS-CoV-2 RdRp, and blocks further incorporation. Using the same molecular insight, we selected the active triphosphate forms of three other anti-viral agents, Alovudine, AZT (an FDA approved HIV/AIDS drug) and Tenofovir alafenamide (TAF, an FDA approved drug for HIV and hepatitis B) for evaluation as inhibitors of SARS-CoV-2 RdRp. We demonstrated the ability of these three viral polymerase inhibitors, 3'-fluoro-3'-deoxythymidine triphosphate, 3'-azido-3'deoxythymidine triphosphate and Tenofovir diphosphate (the active triphosphate forms of Alovudine, AZT and TAF, respectively) to be incorporated by SARS-CoV-2 RdRp, where they also terminate further polymerase extension. These results offer a strong molecular basis for these nucleotide analogues to be evaluated as potential therapeutics for COVID-19.
Example Output: Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase

Example Input: The endoplasmic reticulum (ER) is an architecturally diverse organelle that serves as a membrane source for the replication of multiple viruses. Flaviviruses, including yellow fever virus, West Nile virus, dengue virus, and Zika virus, induce unique single-membrane ER invaginations that house the viral replication machinery 1 . Whether this virus-induced ER remodeling is vulnerable to antiviral pathways is unknown. Here, we show that flavivirus replication at the ER is targeted by the interferon (IFN) response. Through genome-scale CRISPR screening, we uncovered an antiviral mechanism mediated by a functional gene pairing between IFI6, an interferon-stimulated gene (ISG) cloned over 30 years ago 2 , and HSPA5, which encodes the ER-resident HSP70 chaperone BiP. We reveal that IFI6 is an ERlocalized integral membrane effector that is stabilized through interactions with BiP. Mechanistically, IFI6 prophylactically protects uninfected cells by preventing formation of virus-induced ER membrane invaginations. Notably, IFI6 has little effect on other mammalian RNA viruses, including the related Flaviviridae member hepatitis C virus, which replicates in double-membrane vesicles that protrude outward from the ER. These findings support a model in which the IFN response is armed with a membrane-targeted effector that discriminately blocks the establishment of virus-specific ER microenvironments required for replication. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Example Output: A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication HHS Public Access Author manuscript

Example Input: Glycyrrhizin (GL) is known to have various immunomodulating activities and has long been used clinically as an antiallergic and anti-hepatitis agent. While the potency of GL against lung inflammatory diseases has been expected, the effect of GL on the lung has been poorly understood. Lung fibroblasts are known as a potent producer of inflammatory chemokines, IL-8 and eotaxin 1, by which neutrophils and eosinophils are strongly attracted during inflammation. Therefore, we studied the effects of GL on the production of these chemokines using a human fetal lung fibroblast cell line, HFL-1, stimulated with TNFa and IL-4. Moreover, we examined the structure-activity relationships of GL to explore more beneficial compounds. 18a,h-GL inhibited IL-8 dose-dependently and inhibited eotaxin 1 slightly. 18a,h-Glycyrrhetic acid (GA) did not inhibit IL-8 but inhibited eotaxin 1. The effect of 18a,h-glycyrrhetic acid monoglucuronide (MGA) resembled that of 18a,h-GL but was weaker. Both 3h-[(2-O-h-d-glucopyranuronosyl-h-d-glucopyranuronosyl)oxy]-18h-11-deoxo-olean-12-en-30-oic acid (11deoxo-GL) and 3h-[(2-O-h-d-glucopyranuronosyl-h-d-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-oic acid (hetero-GL) exhibited inhibitory activity with significant cytotoxicity. 3h-[(2-O-h-d-Glucopyranuronosyl-h-d-glucopyranuronosyl)oxy]-18h-olean-9,12-dien-30-oic acid (homo-GL) did not have cytotoxicity but its activity was mild like that of 18a,h-GL. 3h-[(2-O-h-d-Glucopyranuronosyl-h-d-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol (hetero-30-OH-GL) and 3h- [(2-O-h-d-glucopyranuronosyl-h-d-glucopyranuronosyl)oxy]-18h-olean-9,12-dien-30-ol (homo-30-OH-GL) showed potent inhib-1567-5769/$ -see front matter D itory effects, at concentrations lower than 18a,h-GL with no significant cytotoxicity. These results suggest that GL-related compounds are effective in reducing chemokine production and that GL-modified compounds including hetero-30-OH-GL and homo-30-OH-GL appear most beneficial in view of their inhibitory capacity with less cytotoxicity. D
Example Output:
Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line