[ILMU MUDAH]: Flu v Cold (selsema)
Ini adalah sedikit penerangan ringkas.Flu = Influenza, jangkitan oleh Influenza viruses (ada beberapa species)
''Selsema'' ialah ''common colds'' ie Cold, jangkitan harian yg selalunya dari viruses ini: Enteroviruses, Rhinoviruses, Coronaviruses dan Adenoviruses
Jadi,''Flu'' bukanlah Selsema. Ianya jauh lebih serious dari Selsema
Adalah common untuk Flu membuat penginapnya dapat jangkitan lain, especially dari bacteria2. Ia juga mudah tersebar (Selsema pun sama juga).
Ini lah sebabnya setiap tahun, penduduk digalakkan mengambil Flu vaccine dan pekerja2 hospital sgt digalakkan untuk mengambilnya (dihospital sy, sesiapa yg ambil Flu vaccine akan diberi token utk Costa coffee ke, bagi scones ke, chocolates ke pens etc). Flu membunuh up to 650,000 manusia setiap tahun.
Dibawah adalah Chart perbezaan symptoms antara Selsema (Cold) dan Flu:
Jadi, Flu adalah lebih teruk dan jauh lebih fatal dari Selsema.
Flu ada vaccine tahunan, Selsema tidak memerlukan vaccine.
Sebahagian besar org yg kena Selsema boleh pergi kerja, cuma bersin2 dan ada rasa kurang sihat sedikit sahaja; mereka yang kena Flu, selalunya cepat dapat rasa bahawa jangkitan mereka kena ini adalah agak teruk Oh...ada terbaca news pasal FLURONA {:1_141:} seribulan replied at 2-1-2022 07:03 AM
Oh...ada terbaca news pasal FLURONA
ya tetapi ianya hanaylah terms untuk kata orang itu kena flu sekaligus dengan covid
sy rasa dalam dua2 ini, flu itu lebih bahaya dan selalunya jauh lebih symptomatic
ipes2 replied at 3-1-2022 07:12 PM
ya tetapi ianya hanaylah terms untuk kata orang itu kena flu sekaligus dengan covid
sy rasa dalam...
Flu lebih bahaya dari corona...fatal...{:1_273:}
ipes2 replied at 3-1-2022 07:12 PM
ya tetapi ianya hanaylah terms untuk kata orang itu kena flu sekaligus dengan covid
sy rasa dalam...
Yg ni Covid pe plak?
Hasil dapatan kajian terbaru penemuan varian B.1.640.2
SARS-CoV-2 variants have become a major virological, epidemiological and clinical concern, particularly with regard to the risk of escape from vaccine-induced immunity. Here we describe the emergence of a new variant.
For twelve SARS-CoV-positive patients living in the same geographical area of southeastern France, qPCR testing that screen for variant-associated mutations showed an atypical combination. The index case returned from a travel in Cameroon.
The genomes were obtained by next-generation sequencing with Oxford Nanopore Technologies on GridION instruments within ≈8 h. Their analysis revealed 46 mutations and 37 deletions resulting in 30 amino acid substitutions and 12 deletions. Fourteen amino acid substitutions, including N501Y and E484K, and 9 deletions are located in the spike protein.
This genotype pattern led to create a new Pangolin lineage named B.1.640.2, which is a phylogenetic sister group to the old B.1.640 lineage renamed B.1.640.1. Both lineages differ by 25 nucleotide substitutions and 33 deletions. The mutation set and phylogenetic position of the genomes obtained here indicate based on our previous definition a new variant we named “IHU”. These data are another example of the unpredictability of the emergence of SARS-CoV-2 variants, and of their introduction in a given geographical area from abroad.
seribulan replied at 5-1-2022 01:43 PM
Yg ni Covid pe plak?
bagus penerangan ini.
tidak dapat baca awal2 dulu
ipes2 replied at 30-6-2022 09:12 PM
bagus penerangan ini.
tidak dapat baca awal2 dulu
Thanks for all tacangs :loveliness: Nasi tambah...
Identification of potent SARS-CoV-2 macrodomain inhibitors
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https://www-azonetwork-com.cdn.ampproject.org/i/s/www.azonetwork.com/themes/clients/images/team/160-4.jpgBy Shanet Susan AlexJun 30 2022Reviewed by Danielle Ellis, B.Sc.
A recent study posted to the bioRxiv* preprint server illustrated the optimization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nonstructural protein 3 (NSP3) macrodomain (Mac) inhibitor based on structure.
https://d2jx2rerrg6sh3-cloudfront-net.cdn.ampproject.org/i/s/d2jx2rerrg6sh3.cloudfront.net/images/news/ImageForNews_718183_16565674176908034.jpgStudy: Structure-based inhibitor optimization for the Nsp3 Macrodomain of SARS-CoV-2. Image Credit: NIAID
BackgroundThe SARS-CoV-2's NSP3 possesses a conserved Mac enzyme called Mac1. It is essential for the lethality and pathogenesis of the virus. Mac1 is a target that has emerged from SARS-CoV-2 that is both very challenging and appealing.
Despite having significant therapeutic potential, few small-molecule Mac1 inhibitors have been reported. Specifically, although Mac1 demonstrated a vital function in the pathogenesis of SARS in animal studies, no inhibitors of any form or reliable chemicals exist for the enzyme.
Fortunately, Mac1 quickly crystallized and exhibited high-resolution diffraction, enabling the fragment-based study of its recognition determinants computationally and empirically. Using this approach, the study's authors previously determined approximately 230 fragment structures. The ligands' binding positions tiled the enzyme's active site, yet despite frequently good ligand efficiencies, no fragments displayed affinities more robust than 180 μM.
About the studyIn the current study, the scientists constructed the molecular determinants of Mac1, which were disclosed by the fragment structures, to find more potent compounds, moving closer to the development of chemical probes and therapeutic leads.
https://d2jx2rerrg6sh3-cloudfront-net.cdn.ampproject.org/i/s/d2jx2rerrg6sh3.cloudfront.net/images/news/ImageForNews_718183_16565671791839806.jpgOverview of the structure-based strategies used to discover ligands that bind to the NSP3 macrodomain of SARS-CoV-2 (Mac1).
The team describes the structure-based creation of a range of chemical scaffolds possessing low-to-sub-micromolar affinities for Mac1 via iterations of computer-assisted design, structural profiling through ultra-high-resolution X-ray protein crystallography, and attachment assessment with in-solution tests. They established effective scaffolds using ultra-large library docking panels with over 450 million compounds and in silico linking of previously acquired fragment hits.
Overall, the present work reports the efforts employed for optimizing priorly defined molecular Mac1 determinants via two methodologies. Initially, the team attempted to link and combine pairs of fragments to produce large compounds that took advantage of many hot spots, reaching high affinities. For this, they applied a novel fragment-linking approach, exploring a virtual collection of 22 billion easily synthesizable molecules.
In the second strategy, the scientists used the hot spots identified by the first fragments to direct the computational coupling of extremely extensive chemical pools of lead-like compounds, which may have greater potency than the fragments coupled in their initial investigation.
Results and conclusionsThe authors reported that 160 Mac1 inhibitory hits consisting of 119 unique scaffolds were found in the present investigation. Furthermore, the crystal structures of 152 Mac1-ligand complexes were identified, often with a resolution of 1 Å or higher.
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The team discovered multiple ligands that caused a significant re-arrangement of the Mac1 active site loop, comprising residues 127 to 136. Relative to the 7 to 12 Å shifts in Phe132 shown in the study, conformational alterations involving Phe132, Ala129, and Asn99 were identified in this loop in the adenosine diphosphate ribose (ADPr)-attached condition and at low pH in the ligand-free enzyme.
Other macrodomains, such as human MacroD1 and PARP14, have also demonstrated everted loop conformations. Despite employing the ADPr-bound condition as a template for docking, the first virtual screening effort failed to find any molecules that stabilized the flipped conformation of Ala129 regardless of the apparent plasticity of this area.
Nevertheless, numerous structures having Ala129 in the flipped condition were discovered during compound optimization. These consisted of LL114 0041, which introduces a carboxylic acid into the phosphate-attaching subsite, and LL123 0020, stabilizing a water molecule in an identical position. Although the alteration in Ala129 was less significant, a comparable water network re-arrangement was observed for Z0828, the docking hit. These ligands present fresh possibilities for structure-informed design projects aiming at the Mac1's phosphate-attaching subsite.
The authors noted that the current attempt yields three key insights. Initially, molecules that incorporated important groups of pairs of fragments and were easily accessible via make-on-demand synthesis were found using an automated fragment-linking and -merging technique in conjunction with searches of ultra-large pools. These efforts resulted in the quick discovery of compounds with low μM affinity, later refined to much lower affinities such as 430 nM, e.g., compound Z8539_0072, a comprehensive improvement of >400-fold relative to the best initial fragment.
Second, templated again by the ligand-identification patterns disclosed by the fragments, molecular docking tests discovered molecules with affinities below 2.5 μM, with some in the mid-μM band, also optimizable to the low μM. Moreover, the best compounds exhibited ligand efficiencies superior to even the combined fragments.
Thirdly, despite most molecules being anionic harboring high polar surface areas decreasing cell permeability, structure-based optimization identified analogs like alcohols, ureas, and phenols possessing few hydrogen-donating groups, enabling swapping the anionic warheads for neutral ones. This shows that it might be possible to increase cell membrane permeability for several scaffold classes considered herein.
Altogether, the researchers stated that the structure-activity connections discovered through this work could serve as a model for future Mac1-targeting drug development. From a technical viewpoint, a dataset for benchmarking and enhancing computational tools for the discovery of drugs, such as free energy perturbation, was created by the abundance of structure-activity relationships paired with X-ray crystal structures for most molecules discovered in the research. The substances and configurations presented in this study will facilitate the development of first-in-class antiviral medicines that target the NSP3 Mac of SARS-CoV-2 from a therapeutic standpoint.
*Important noticebioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information
seribulan replied at 1-7-2022 09:58 AM
Nasi tambah...
Identification of potent SARS-CoV-2 macrodomain inhibitors
eh bila awak tulis ini?
tidak dapat notifications pon
good explanation, albeit a tad long
ipes2 replied at 5-7-2022 05:17 AM
eh bila awak tulis ini?
tidak dapat notifications pon
good explanation, albeit a tad long
Notification memang x kuar kat thread lama {:1_141:}
seribulan replied at 5-7-2022 06:30 AM
Notification memang x kuar kat thread lama
kan ada time ada issues kejap dulu tu
ipes2 replied at 6-7-2022 04:51 AM
kan ada time ada issues kejap dulu tu
:D haah...yang baharu pun kadang ada isu... seribulan replied at 6-7-2022 07:04 AM
haah...yang baharu pun kadang ada isu...
sy pun selalu tak dapat notification
contoh, utk ini
sy hanya cek secara random je, tu sebab nmpk
ipes2 replied at 15-8-2022 04:02 AM
sy pun selalu tak dapat notification
contoh, utk ini
sy hanya cek secara random je, tu sebab nmpk
Eh dejavu lak {:1_141:}
seribulan replied at 15-8-2022 09:43 AM
Eh dejavu lak
awak pon sama jugak koh ha ha
sekarang ni pon sy masih tak dpt notif in some cases
ipes2 replied at 20-8-2022 11:19 PM
awak pon sama jugak koh ha ha
sekarang ni pon sy masih tak dpt notif in some cases
Dah boleh nampak di noti pulak :)
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