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About 7,570 results

A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry ...
https://doi.org/10.1073/pnas.2108728118
Proceedings of the National Academy of Sciences of the Un... Mahoney M, Damalanka VC et. al.

Oct 13th, 2021 - The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to substrate specificity screening of TMPRSS2, we ha...

Complete lung agenesis caused by complex genomic rearrangements with neo-TAD formation ...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460539
Human Genetics; Melo US, Piard J et. al.

Aug 27th, 2021 - During human organogenesis, lung development is a timely and tightly regulated developmental process under the control of a large number of signaling molecules. Understanding how genetic variants can disturb normal lung development causing different lung malformations is a major goal for dissecting molecular mechanisms during embryogenesis. Here, through exome sequencing (ES), array CGH, genome...

In situ ultrastructures of two evolutionarily distant apicomplexan rhoptry secretion sy...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371170
Nature Communications; Mageswaran SK, Guérin A et. al.

Aug 19th, 2021 - Parasites of the phylum Apicomplexa cause important diseases including malaria, cryptosporidiosis and toxoplasmosis. These intracellular pathogens inject the contents of an essential organelle, the rhoptry, into host cells to facilitate invasion and infection. However, the structure and mechanism of this eukaryotic secretion system remain elusive. Here, using cryo-electron tomography and subtom...

Correlative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324836
Nature Communications; Mendonça L, Howe A et. al.

Aug 1st, 2021 - Since the outbreak of the SARS-CoV-2 pandemic, there have been intense structural studies on purified viral components and inactivated viruses. However, structural and ultrastructural evidence on how the SARS-CoV-2 infection progresses in the native cellular context is scarce, and there is a lack of comprehensive knowledge on the SARS-CoV-2 replicative cycle. To correlate cytopathic events indu...

A synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324831
Nature Communications; Li T, Cai H et. al.

Aug 1st, 2021 - SARS-CoV-2, the causative agent of COVID-191, features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein1-6. Neutralizing antibodies that block RBD-ACE2 interaction are candidates for the development of targeted therapeutics7-17. Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages in bioavailability, amenability, and production and storage owing...

Presumed SARS-CoV-2 Viral Particles in the Human Retina of Patients With COVID-19.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323055
JAMA Ophthalmology; Araujo-Silva CA, Marcos AAA et. al.

Jul 30th, 2021 - The presence of the SARS-CoV-2 virus in the retina of deceased patients with COVID-19 has been suggested through real-time reverse polymerase chain reaction and immunological methods to detect its main proteins. The eye has shown abnormalities associated with COVID-19 infection, and retinal changes were presumed to be associated with secondary microvascular and immunological changes. To demonst...

SARS-CoV-2 Initiates Programmed Cell Death in Platelets.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409903
Circulation Research; Koupenova M, Corkrey HA et. al.

Jul 24th, 2021 - [Figure: see text].

Neuroprotection of the Inner Retina Also Prevents Secondary Outer Retinal Pathology in ...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300060
Investigative Ophthalmology & Visual Science; Kumar S, Ramakrishnan H et. al.

Jul 24th, 2021 - We examined structural and functional changes in the outer retina of a mouse model of glaucoma. We examined whether these changes are a secondary consequence of damage in the inner retina and whether neuroprotection of the inner retina also prevents outer retinal changes. We used an established microbead occlusion model of glaucoma whereby intraocular pressure (IOP) was elevated. Specific antib...

SARS-CoV-2: preliminary study of infected human nasopharyngeal tissue by high resolutio...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286443
Virology Journal; Mondeja B, Valdes O et. al.

Jul 20th, 2021 - The novel coronavirus SARS-CoV-2 is the etiological agent of COVID-19. This virus has become one of the most dangerous in recent times with a very high rate of transmission. At present, several publications show the typical crown-shape of the novel coronavirus grown in cell cultures. However, an integral ultramicroscopy study done directly from clinical specimens has not been published. Nasopha...

SARS-CoV-2 infection induces the dedifferentiation of multiciliated cells and impairs m...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285531
Nature Communications; Robinot R, Hubert M et. al.

Jul 18th, 2021 - Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define the parameters controlling the severity of COVID-19. Here we examine the functional and structural consequences of SARS-CoV-2 infection in a reconstructed human bronchial epithelium model. SARS-CoV-2 replication causes a transient decrease in epithelial barrier function and disruption of tight junctions, th...

TSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275687
Nature Communications; Alesi N, Akl EW et. al.

Jul 14th, 2021 - Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1). Transcription factor EB (TFEB), a master regulator of lysosome biogenesis, is negatively regulated by mTORC1 through a RAG GTPase-dependent phosphorylation. Here we show that lysosomal biogenesis is increased in TSC-associated renal tumors...

Structural basis of LAIR1 targeting by polymorphic Plasmodium RIFINs.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270905
Nature Communications; Xu K, Wang Y et. al.

Jul 11th, 2021 - RIFIN, a large family of Plasmodium variant surface antigens, plays a crucial role in malaria pathogenesis by mediating immune suppression through activation of inhibitory receptors such as LAIR1, and antibodies with LAIR1 inserts have been identified that bind infected erythrocytes through RIFIN. However, details of RIFIN-mediated LAIR1 recognition and receptor activation have been unclear. He...

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217502
Nature Communications; Evers F, Cabrera-Orefice A et. al.

Jun 23rd, 2021 - Our current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes across the pathogenic asexual blood stages and t...

Structural basis for SARS-CoV-2 envelope protein recognition of human cell junction pro...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187709
Nature Communications; Chai J, Cai Y et. al.

Jun 10th, 2021 - The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has created global health and economic emergencies. SARS-CoV-2 viruses promote their own spread and virulence by hijacking human proteins, which occurs through viral protein recognition of human targets. To understand the structural basis for SARS-CoV-2 viral-host protein recognition, here we use cryo-electron microscopy (cryo-EM) to determ...

Proline/arginine dipeptide repeat polymers derail protein folding in amyotrophic latera...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184751
Nature Communications; Babu M, Favretto F et. al.

Jun 9th, 2021 - Amyotrophic lateral sclerosis and frontotemporal dementia are two neurodegenerative diseases with overlapping clinical features and the pathological hallmark of cytoplasmic deposits of misfolded proteins. The most frequent cause of familial forms of these diseases is a hexanucleotide repeat expansion in the non-coding region of the C9ORF72 gene that is translated into dipeptide repeat polymers....

A metal ion orients SARS-CoV-2 mRNA to ensure accurate 2'-O methylation of its first nu...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172916
Nature Communications; Viswanathan T, Misra A et. al.

Jun 4th, 2021 - The SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2'-OH of the first transcribed nucleotide of the viral mRNA by covalently attaching a methyl group to it. The 2'-O methylation of the first nucleotide converts the status of mRNA cap from Cap-0 to Cap-1, and thus, helps the virus evade immune surveillance in host cells. Here, we report two structures of nsp16/nsp10 representing pre- and pos...

Cryo-EM to visualize the structural organization of viruses.
https://doi.org/10.1016/j.coviro.2021.04.011
Current Opinion in Virology; de Oliveira GA, Silva JL

Jun 1st, 2021 - It is intriguing to think that over millions of years, groups of nucleic acids got the chance to hold together with groups of proteins to build up what today is called a virus. Their only goal is to guarantee a successful replication inside a host. If their genome information is preserved, the task is accomplished. Viruses have evolved to infect organisms and propagate with high degree of adapt...

Uncovering Modifier Genes of X-Linked Alport Syndrome Using a Novel Multiparent Mouse M...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455275
Journal of the American Society of Nephrology : JASN; Takemon Y, Wright V et. al.

May 29th, 2021 - Mutations in COL4A5 are responsible for 80% of cases of X-linked Alport Syndrome (XLAS). Although genes that cause AS are well characterized, people with AS who have similar genetic mutations present with a wide variation in the extent of kidney impairment and age of onset, suggesting the activities of modifier genes. We created a cohort of genetically diverse XLAS male and female mice using th...

Esophageal carcinoma cell-excreted exosomal uc.189 promotes lymphatic metastasis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202844
Aging Ding Z, Yan Y et. al.

May 25th, 2021 - Most cancers are old age-related diseases. Patients with lymphatic metastasis have an extremely poor prognosis in esophageal cancers (ECs). Previous studies showed ultraconserved RNAs are involved in tumorigenesis and ultraconserved RNA 189 (uc.189) served as an oncogene in cervical cancer, but the effect of exosomal uc.189 in esophageal squamous cell carcinoma (ESCC) remains undefined. This st...

Micro-Computed Tomography Analysis of the Human Tuberculous Lung Reveals Remarkable Het...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491258
American Journal of Respiratory and Critical Care Medicine; Wells G, Glasgow JN et. al.

May 21st, 2021 - Rationale: Our current understanding of tuberculosis (TB) pathophysiology is limited by a reliance on animal models, the paucity of human TB lung tissue, and traditional histopathological analysis, a destructive two-dimensional approach that provides limited spatial insight. Determining the three-dimensional (3D) structure of the necrotic granuloma, a characteristic feature of TB, will more acc...