Design, Synthesis and Antifungal Activity of Novel Benzofuran-Triazole Hybrids
Antifungal activity, N-myristoyltransferase, benzofuran, 1, 2, 3-triazole, Click chemistry, molecule hybrid
A series of novel benzofuran-triazole hybrids was designed and synthesized by click chemistry, and their structures were characterized by HRMS, FTIR and NMR. The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against five strains of pathogenic fungi. The result indicated that the target compounds exhibited moderate to satisfactory activity. Furthermore, molecular docking was performed to investigate the binding affinities and interaction modes between the target compound and N-myristoyltransferase. Based on the results, preliminary structure activity relationships (SARs) were summarized to serve as a foundation for further investigation.
Zhen Liang, Hang Xu, Ye Tian, Mengbi Guo, Xin Su, Chun Guo
MERS may not be SARS; but India is still vulnerable
Synthesis and Antiviral Activity of Novel 1,4-Pentadien-3-one Derivatives Containing a 1,3,4-Thiadiazole Moiety
1, 4-pentadien-3-one derivatives, 3, 4-thiadiazole, Synthesis, anti-TMV, anti-CMV
1,4-Pentadien-3-one derivatives derived from curcumin possess excellent inhibitory activity against plant viruses. On the basis of this finding, a series of novel 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety were designed and synthesized, and their structures confirmed by IR, 1H-NMR, and 13C-NMR spectroscopy and elemental analysis. The antiviral activities of the title compounds were evaluated against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. The assay results showed that most of compounds had remarkable antiviral activities against TMV and CMV, among which compounds 4b, 4h, 4i, 4k, 4o, and 4q exhibited good curative, protection, and inactivation activity against TMV. Compounds 4h, 4i, 4k, 4l, 4o, and 4q exhibited excellent protection activity against TMV, with EC50 values of 105.01, 254.77, 135.38, 297.40, 248.18, and 129.87 μg/mL, respectively, which were superior to that of ribavirin (457.25 µg/mL). In addition, preliminary SARs indicated that small electron-withdrawing groups on the aromatic ring were favorable for anti-TMV activity. This finding suggests that 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety may be considered as potential lead structures for discovering new antiviral agents.
Lu Yu, Xiuhai Gan, Dagui Zhou, Fangcheng He, Song Zeng, Deyu Hu
The Coronavirus Nucleocapsid Is a Multifunctional Protein
Nucleocapsid protein, coronavirus assembly, coronavirus N, intracellular localization, protein topology
The coronavirus nucleocapsid (N) is a structural protein that forms complexes with genomic RNA, interacts with the viral membrane protein during virion assembly and plays a critical role in enhancing the efficiency of virus transcription and assembly. Recent studies have confirmed that N is a multifunctional protein. The aim of this review is to highlight the properties and functions of the N protein, with specific reference to (i) the topology; (ii) the intracellular localization and (iii) the functions of the protein.
Ruth McBride, Marjorie van Zyl, Burtram C. Fielding
Elicitation of broadly neutralizing antibodies against HIV-1 – the germline/maturation hypothesis
IgM, 454 sequencing, broadly neutralizing antibody, HIV-1/vaccine, germline antibody
We have previously observed that all known broadly neutralizing antibodies (bnAbs) against HIV-1 are highly divergent from their putative germline predecessors in contrast to bnAbs against henipaviruses and SARS coronavirus, which are much less divergent from their germline counterparts. We have hypothesized that because the germline antibodies are so different compared to the highly somatically mutated HIV-1 bnAbs they may not bind to the Env. This led us to the hypothesis that the immunogenicity of the highly conserved epitopes on the HIV-1 envelope glycoproteins (Envs) is reduced or eliminated by their very weak or absent interactions with germline antibodies. Thus immune responses leading to elicitation of bnAbs may not be initiated and/or sustained; even if they are, the maturation pathways are so complex that prolonged periods of time may be required for elicitation of such bnAbs. In support of the hypothesis, our initial experiments showed that germline-like precursors of several bnAbs do not bind to their epitopes. Recently, a number of research groups working in the HIV vaccine field have obtained data supporting and further expanding the germline/maturation hypothesis. Vaccine immunogens that could bind putative germline antibody predecessors of known bnAbs were successfully generated. However, guiding the immune system through the exceptionally complex antibody maturation pathways in order to elicit those bnAbs remains a major challenge. Here, we summarize developments in the HIV-1 vaccine field based on the germline/maturation hypothesis including our recent data demonstrating germline-like VRC01 antibodies in a human cord blood IgM library.
Prabakaran ePonraj, Weizao eChen, Dimiter S. Dimitrov
Polarimetric Scattering Properties of Landslides in Forested Areas and the Dependence on the Local Incidence Angle
Synthetic Aperture Radar (SAR), polarimetry, power decomposition, co-polarization correlation coefficient, local incidence angle, landslide
This paper addresses the local incidence angle dependence of several polarimetric indices corresponding to landslides in forested areas. Landslide is deeply related to the loss of human lives and their property. Various kinds of remote sensing techniques, including aerial photography, high-resolution optical satellite imagery, LiDAR and SAR interferometry (InSAR), have been available for landslide investigations. SAR polarimetry is potentially an effective measure to investigate landslides because fully-polarimetric SAR (PolSAR) data contain more information compared to conventional single- or dual-polarization SAR data. However, research on landslide recognition utilizing polarimetric SAR (PolSAR) is quite limited. Polarimetric properties of landslides have not been examined quantitatively so far. Accordingly, we examined the polarimetric scattering properties of landslides by an assessment of how the decomposed scattering power components and the polarimetric correlation coefficient change with the local incidence angle. In the assessment, PolSAR data acquired from different directions with both spaceborne and airborne SARs were utilized. It was found that the surface scattering power and the polarimetric correlation coefficient of landslides significantly decrease with the local incidence angle, while these indices of surrounding forest do not. This fact leads to establishing a method of effective detection of landslide area by polarimetric information.
Takashi Shibayama, Yoshio Yamaguchi, Hiroyoshi Yamada
Human Coronaviruses: A Review of Virus–Host Interactions
human coronavirus, virus–host interactions, apoptosis, Innate Immunity, ER stress, MAPK, NF-κB
Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs.
Yvonne Xinyi Lim, Yan Ling Ng, James P Tam, Ding Xiang Liu
European Bats as Carriers of Viruses with Zoonotic Potential
bats, Zoonoses, virus, virus discovery, emerging infectious disease
Bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (Marburg virus, Nipah virus, Hendra virus, Rabies virus, and coronaviruses). While numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in European bats. Although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are conducted. At present, it is assumed that the risk posed by bats to the general public is rather low. In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. All European bat species and their roosts are legally protected and some European species are even endangered. Nevertheless, the increasing public fear of bats and their viruses is an obstacle to their protection. Educating the public regarding bat lyssaviruses might result in reduced threats to both the public and the bats.
Antigen Production in Plant to Tackle Infectious Diseases Flare Up: the Case of SARS
SARS-CoV, M protein, severe acute respiratory syndrome (SARS), emerging infectious disease, Plant expression, N protein
Severe Acute Respiratory Syndrome (SARS) is a dangerous infection with pandemic potential. It emerged in 2002 and its aetiological agent, the SARS Coronavirus (SARS-CoV), crossed the species barrier to infect humans, showing high morbidity and mortality rates. No vaccines are currently licensed for SARS-CoV and important efforts have been performed during the first outbreak to develop diagnostic tools. Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. For the M protein, this is the first description of production in plants, while for plant-derived N protein we demonstrate that it is recognized by sera of patients from the SARS outbreak in Hong Kong in 2003. The availability of recombinant N and M proteins from plants opens the way to further evaluation of their potential utility for the development of diagnostic and protection/therapy tools to be quickly manufactured, at low cost and with minimal risk, to face potential new highly infectious SARS-CoV outbreaks.
Olivia C eDemurtas, Silvia eMassa, Elena eIlliano, Domenico eDe Martinis, Paul KS eChan, Paola eDi Bonito, Rosella eFranconi
New genus, three new species and new records of Herpyllobiidae Hansen, 1892 (Crustacea, Copepoda) parasites of polychaetes from Antarctica
parasitic Copepoda, Herpyllobiidae, Herpyllobius, Eurysilenium, Gottoniella, Antarctica, Polynoidae
During the Antarctic Polarstern cruises ANT XIX/3 (ANDEEP-I), XIX/5 (LAMPOS), and XXI/2 (BENDEX) new material of symbiotic copepods associated with polynoid polychaetes was collected. Here the authors present results for the highly modified family Herpyllobiidae Hansen, 1892. New records of Herpyllobius antarcticus Vanhöffen, 1913 and Herpyllobius polarsterni López-González, Bresciani and Conradi, 2000 are provided from the eastern Weddell Sea and Bouvet Island respectively. A new species of the genus Eurysilenium Sars, 1870, E. australis, is described from specimens collected at the eastern Weddell Sea. A new genus, Gottoniella gen. nov., is proposed to include two species, G. antarctica sp. nov. and G. andeepi sp. nov., described from material collected from the Weddell Sea and Scotia Arc.
Pablo J. López-González, José Bresciani, Mercedes Conradi
Consejo Superior de Investigaciones Científicas