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: Main point: Hydroxychloroquine was found to be more potent than chloroquine at inhibiting SARS-CoV-2 in vitro. Hydroxychloroquine sulfate 400 mg given twice daily for 1 day, followed by 200 mg twice daily for 4 more days is recommended to treat SARS-CoV-2 infection. Abstract Background. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first broke out in Wuhan (China) and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. Methods. The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells. Physiologically-based pharmacokinetic models (PBPK) were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen whilst considering the drug's safety profile. Results. Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than chloroquine (EC50=5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. Hydroxychloroquine was found to be more potent than chloroquine to 4 / 25 inhibit SARS-CoV-2 in vitro.

A: In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
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Q: Ca 2+ is one of the most universal and versatile signaling molecules and is involved in almost every aspect of cellular processes. Viruses are adept at utilizing the universal Ca 2+ signal to create a tailored cellular environment that meets their own demands. This review summarizes most of the known mechanisms by which viruses perturb Ca 2+ homeostasis and utilize Ca 2+ and cellular Ca 2+ -binding proteins to their benefit in their replication cycles. Ca 2+ plays important roles in virion structure formation, virus entry, viral gene expression, posttranslational processing of viral proteins and virion maturation and release. As part of the review, we introduce an algorithm to identify linear "EF-hand" Ca 2+ -binding motifs which resulted in the prediction of a total of 93 previously unrecognized Ca 2+ -binding motifs in virus proteins. Many of these proteins are nonstructural proteins, a class of proteins among which Ca 2+ interactions had not been formerly appreciated. The presence of linear Ca 2+ -binding motifs in viral proteins enlarges the spectrum of Ca 2+ -virus interplay and expands the total scenario of viral calciomics. (J.J. Yang). for structural integrity or functionality; and (3) critical virus-host interactions depend on cellular Ca 2+ -regulated proteins or pathways. This review, which aims to stimulate future studies on the roles of Ca 2+ in virus infection, is focused on such interplay by highlighting recent discoveries in the biological roles of Ca 2+ in virus infection. 0143-4160/$ -see front matter

A: Viral calciomics: Interplays between Ca 2+ and virus
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Q: The viral RNA-dependent RNA polymerase (RdRp) is essential for multiplication of all RNA viruses. The sequence diversity of an RNA virus population contributes to its ability to infect the host. This diversity emanates from errors made by the RdRp during RNA synthesis. The physical basis for RdRp fidelity is unclear but is linked to conformational changes occurring during the nucleotide-addition cycle. To understand RdRp dynamics that might influence RdRp function, we have analyzed all-atom molecular dynamics (MD) simulations on the nanosecond timescale of four RdRps from the picornavirus family that exhibit 30-74% sequence identity. Principal component analysis showed that the major motions observed during the simulations derived from conserved structural motifs and regions of known function. Dynamics of residues participating in the same biochemical property, for example RNA binding, nucleotide binding or catalysis, were correlated even when spatially distant on the RdRp structure. The conserved and correlated dynamics of functional, structural elements suggest co-evolution of dynamics with structure and function of the RdRp. Crystal structures of all picornavirus RdRps exhibit a template-nascent RNA duplex channel too small to fully accommodate duplex RNA. Simulations revealed opening and closing motions of the RNA and NTP channels, which might be relevant to NTP entry, PP i exit and translocation. A role for nanosecond timescale dynamics in RdRp fidelity is supported by altered dynamics of the high-fidelity G64S derivative of PV RdRp relative to wild-type enzyme. . Table S1 lists the amino acid sequence numbering for the different subdomains, motifs A-G, and functional regions I-III of the RdRps used in the study. Figure S1 shows the structure-based sequence alignment for the different RdRps. Figure S2 shows the time series plot of RMSD for the different simulated systems. Figure S3 shows representative structures for the clusters C1-C4 of PV RdRp in two views. Figure S4 shows snapshots corresponding to the beginning, middle, and end of the simulation trajectories of the four RdRps. Figure S5 compares analyzed B-factors for the different simulated RdRps. Figure S6 compares the per-residue RMSD analysis for the different simulated RdRps. Figure S7 compares the radius of gyration analysis for the different RdRps. Figure S8 compares the RNA channel width in the different simulated RdRps. Figure S9 compares PCA and DCCM analyses from 25 and 52 ns simulations of PV RdRp. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript.

A:
Author manuscript; available in PMC
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