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Neplanocin A analogs have attracted attention in the fields of biological and medicinal chemistry due to their potent and broad-spectrum antiviral and antitumor activities. To further explore their potential as therapeutic agents, an alternative and efficient synthesis of fluoro-neplanocin A analogs has been developed by employing stereoselective electrophilic fluorination and palladium-catalyzed dehydrosilylation as key steps. With respect to previous syntheses, the present synthetic methodology provides easy access to key intermediates that could contribute to expanding further the structure–activity relationship studies of neplanocin A analogs.

We have reported on aristeromycin (1) and 6'-fluorinated-aristeromycin analogues (2), which are active against RNA viruses such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), and Chikungunya virus (CHIKV). However, these exhibit substantial cytotoxicity. As this cytotoxicity may be attributed to 5'-phosphorylation, we designed and synthesized one-carbon homologated 6'-fluorinated-aristeromycin analogues. This modification prevents 5'-phosphorlyation by cellular kinases, whereas the inhibitory activity towards S-adenosyk-homocysteine (SAH) hydrolase will be retained. The enantiomerically pure 6'-fluorinated-5'-homoaristeromycin analogues 3a-e were synthesized via the electrophilic fluorination of the silyl enol ether with Selectfluor, using a base-build up approach as the key steps. All synthesized compounds exhibited potent inhibitory activity towards SAH hydrolase, among which 6'-beta-fluoroadenosine analogue 3a was the most potent (IC50 = 0.36 mu M). Among the compounds tested, 6'-beta-fluoro-homoaristeromycin 3a showed potent antiviral activity (EC50 = 0.12 mu M) against the CHIKV, without noticeable cytotoxicity up to 250 mu M. Only 3a displayed anti-CHIKV activity, whereas both3a and 3b inhibited SAH hydrolase with similar IC50 values (0.36 and 0.37 mu M, respectively), which suggested that 3a's antiviral activity did not merely depend on the inhibition of SAH hydrolase. This is further supported by the fact that the antiviral effect was specific for CHIKV and some other alphaviruses and none of the homologated analogues inhibited other RNA viruses, such as SARS-CoV, MERS-CoV, and ZIKV. The potent inhibition and high selectivity index make 6'-beta-fluoro-homoaristeromycin (3a) a promising new template for the development of antivirals against CHIKV, a serious re-emerging pathogen that has infected millions of people over the past 15 years. (C) 2019 Elsevier Masson SAS. All rights reserved.

Recently, Choe & Cheng (2002) have demonstrated that multiple magnetic flux systems with closed configurations can have more magnetic energy than the corresponding open magnetic fields. In relation to this issue, we have addressed two questions: (1) how much fraction of eruptive solar active regions shows multiple flux system features, and (2) what winding angle could be an eruption threshold. For this investigation, we have taken a sample of 105 front-side halo CMEs, which occurred from 1996 to 2001, and whose source regions were located near the disk center, for which magnetic polarities in SOHO/MDI magnetograms are clearly discernible. Examining their soft X-ray images taken by Yohkoh SXT in pre-eruption stages, we have classified these events into two groups: multiple flux system events and single flux system events. It is found that 74% (78/105) of the sample events show multiple flux system features. Comparing the field configuration of an active region with a numerical model, we have also found that the winding angle of the eruptive flux system is slightly above 1.5π.

The aim of this paper is to describe the results of the study on the extreme-ultra-violet (EUV) solar telescope, which is designed for a possible satellite mission. Since the EUV band can not be observed on the ground, the observation in EUV should be performed in space using a satellite or a rocket. Design of the Extreme-Ultra-Violet solar Telescope (EUVT) in this study is based on ``Designing a small-sized engineering model of solar EUV telescope for a Korean satellite" (Han et al. 2001). Our EUVT design is satisfied with the requirements for a satellite in size and input voltage. The major goal of the study is to confirm if we can detect the specific wavelength (58.4nm to 62.9nm) with the EUVT. We describe re-designing of the EUVT to decrease a shelter ratio. Also we describe the technics in the optic system and the detector, which were used to manufacture the EUVT. We explain the detective program, which is to calculate the amount of the solar radiation, and the image data processing system.

The KSR-3 magnetometers consist of the fluxgate magnetometer (MAG/AIM) for acquiring the rocket flight attitude information, and the search-coil magnetometer (MAG/SIM) for the observation of the Earth's magnetic fluctuations. The position (latitude, longitude, and height) and flight condition (the transformation angle) of the rocket is measured after the data based on these two magnetometers are compared with IGRF. The gap in the vector of magnetic field between the position of the launching point and an impact point is taken into account in data reduction. Angular variation of pitch, yaw, and roll can be researched when the data is applied to the coordinate system of the rocket.

Alphaviruses are arthropod-borne, positive-stranded RNA viruses capable of causing severe disease with high morbidity. Chikungunya virus (CHIKV) is an alphavirus that causes a febrile illness which can progress into chronic arthralgia. The current lack of vaccines and specific treatment for CHIKV infection underscores the need to develop new therapeutic interventions. To discover new antiviral agents, we performed a compound screen in cell culture-based infection models and identified two carbocyclic adenosine analogues, 6′-β-fluoro-homoaristeromycin (FHA) and 6′-fluoro-homoneplanocin A (FHNA), that displayed potent activity against CHIKV and Semliki Forest virus (SFV) with 50% effective concentrations in the nanomolar range at nontoxic concentrations., Alphaviruses are arthropod-borne, positive-stranded RNA viruses capable of causing severe disease with high morbidity. Chikungunya virus (CHIKV) is an alphavirus that causes a febrile illness which can progress into chronic arthralgia. The current lack of vaccines and specific treatment for CHIKV infection underscores the need to develop new therapeutic interventions. To discover new antiviral agents, we performed a compound screen in cell culture-based infection models and identified two carbocyclic adenosine analogues, 6′-β-fluoro-homoaristeromycin (FHA) and 6′-fluoro-homoneplanocin A (FHNA), that displayed potent activity against CHIKV and Semliki Forest virus (SFV) with 50% effective concentrations in the nanomolar range at nontoxic concentrations. The compounds, designed as inhibitors of the host enzyme S-adenosylhomocysteine (SAH) hydrolase, impeded postentry steps in CHIKV and SFV replication. Selection of FHNA-resistant mutants and reverse genetics studies demonstrated that the combination of mutations G230R and K299E in CHIKV nonstructural protein 1 (nsP1) conferred resistance to the compounds. Enzymatic assays with purified wild-type (wt) SFV nsP1 suggested that an oxidized (3′-keto) form, rather than FHNA itself, directly inhibited the MTase activity, while a mutant protein with the K231R and K299E substitutions was insensitive to the compound. Both wt nsP1 and the resistant mutant were equally sensitive to the inhibitory effect of SAH. Our combined data suggest that FHA and FHNA inhibit CHIKV and SFV replication by directly targeting the MTase activity of nsP1, rather than through an indirect effect on host SAH hydrolase. The high potency and selectivity of these novel alphavirus mRNA capping inhibitors warrant further preclinical investigation of these compounds.