Truly Man's Best Friend: Canine Cancers Drive Drug Repurposing in Osteosarcoma

This article explores the representation of guilt in six recent young adult novels, in which it is suggested that teen protagonists still experience guilt in relation to their emerging non-normative sexual identities. The experience of guilt may take several different forms, but all dealt with here are characterised by guilt without agency – that is, the protagonist has not deliberately said or done anything to cause harm to another. In a first pair of novels, guilt is depicted as a consequence of internalised homophobia, with which protagonists must at least partly identify. In a second group, protagonists seem to experience a form of separation guilt from an early age because they fail to conform to the norms of the family. Certain events external to the teen protagonist, and for which they cannot be held responsible, then trigger serious depressive episodes, which jeopardise the protagonist's positive identity development. Finally, characters are depicted as experiencing a form of survivor guilt. A gay protagonist survives the events of 9/11 but endures a breakdown, and, in a second novel, a lesbian protagonist narrates her coming to terms with the death of her best friend.

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Drug Repurposing Studies Targeting SARS-nCoV2: An Ensemble Docking Approach on Drug Target 3C-like Protease (3CLpro)

10.26434/chemrxiv.12228831 ◽

2020 ◽

Author(s):

Shruti Koulgi ◽

Vinod Jani ◽

Mallikarjunachari Uppuladinne ◽

Uddhavesh Sonavane ◽

Asheet Kumar Nath ◽

...

Keyword(s):

Drug Repurposing ◽

Drug Binding ◽

Ensemble Docking ◽

Drug Molecules ◽

Drug Binding Site ◽

Main Protease ◽

Docking Approach ◽

Novel Coronavirus ◽

Markov State Modeling ◽

Viral Polyprotein

The COVID-19 pandemic has been responsible for several deaths worldwide. The causative agent behind this disease is the Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-nCoV2). SARS-nCoV2 belongs to the category of RNA viruses. The main protease, responsible for the cleavage of the viral polyprotein is considered as one of the hot targets for treating COVID-19. Earlier reports suggest the use of HIV anti-viral drugs for targeting the main protease of SARS-CoV, which caused SARS in the year 2002-03. Hence, drug repurposing approach may prove to be useful in targeting the main protease of SARS-nCoV2. The high-resolution crystal structure of 3CLpro (main protease) of SARS-nCoV2 (PDB ID: 6LU7) was used as the target. The Food and Drug Administration (FDA) approved and SWEETLEAD database of drug molecules were screened. The apo form of the main protease was simulated for a cumulative of 150 ns and 10 μs open source simulation data was used, to obtain conformations for ensemble docking. The representative structures for docking were selected using RMSD-based clustering and Markov State Modeling analysis. This ensemble docking approach for main protease helped in exploring the conformational variation in the drug binding site of the main protease leading to efficient binding of more relevant drug molecules. The drugs obtained as best hits from the ensemble docking possessed anti-bacterial and anti-viral properties. Small molecules with these properties may prove to be useful to treat symptoms exhibited in COVID-19. This in-silico ensemble docking approach would support identification of potential candidates for repurposing against COVID-19.

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Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

10.31222/osf.io/78mbt ◽

2020 ◽

Author(s):

Sanaa Bardaweel

Keyword(s):

Clinical Trials ◽

Drug Discovery ◽

Antimalarial Drug ◽

Drug Repurposing ◽

Spike Protein ◽

Diabetic Patients ◽

Potential Drug ◽

Chemokine Production ◽

Drug Discovery And Development ◽

Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

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Yury Nagibin and shadows of the Niernsee House

Voprosy literatury ◽

10.31425/0042-8795-2020-3-42-60 ◽

2020 ◽

pp. 42-60

Author(s):

S. N. Liutova ◽

I. I. Dronova

Keyword(s):

Life Story ◽

Manufacturing Plant ◽

The Real ◽

Best Friend ◽

Real People ◽

State Archives ◽

First Time

The article reveals the names of the prototypes of certain characters in Nagibin’s long story My Golden Mother-in-Law [Moya zolotaya tyoshcha] (the mother-in-law being A. Likhachyova, the wife of the director of the Moscow Car Manufacturing Plant ZIL). For the first time we read the names and learn about the destiny of M. and L. Kostromin, the real people behind the characters of Matvey Matveevich, the neighbour, and Nina Petrovna, the female protagonist’s best friend. The life story of these personalities, residents of the legendary Niernsee House in Bolshoy Gnezdnikovsky Lane, enables the authors, who are related to L. Kostromina, to explain the underpinnings of the relationships between the prototypes of Nagibin’s characters, often a mystery for the writer himself, and share first-hand accounts that confirm his amazing flair for imagination. The article uses materials of family lore, the authors’ private archive (letters and photographs), as well as hitherto unsearched materials from state archives.

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