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Transcriptomics identifies possible COVID-19 therapies

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4 years ago

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Transcriptomics identifies possible COVID-19 therapies

By the usage of a various set of transcriptomic SARS-CoV-2 signatures, US researchers placed to apply their formerly advanced drug repositioning pipeline to pinpoint capacity drug applicants for the remedy of coronavirus disease (COVID-19). The take a look at is presently to be had at the bioRxiv* preprint server.
While many efforts are presently underway to perceive capacity treatment options concentrated on numerous components of COVID-19, as a result of the extreme acute breathing syndrome coronavirus 2 (SARS-CoV-2), there may be nevertheless a loss of clinically tested procedures to be had in our armamentarium.
Drug repositioning is one of the procedures that has been appreciably explored in the course of this pandemic. More specifically, high-throughput screening pipelines had been placed forth as possible techniques to check drug applicants as they’re diagnosed quickly.
A comparable technique has been taken through a set of scientists led through Dr. Brian L. Le from the Department of Pediatrics and Bakar Computational Health Sciences Institute on the University of California San Francisco.
In this take a look at, the researchers implemented their current computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly to be had RNA-sequencing (RNA-seq) records. The transcriptomic records has been generated from awesome forms of tissues, because of this that they may are expecting therapeutics for every signature after which integrate the results.
Moreover, validity turned into showed through displaying sixteen in their drug hits’ inhibitory outcomes, that may notably opposite more than one SARS-CoV-2 profiles in stay antiviral assays. Two forms of mobileular traces had been used: Calu-3 (human lung mobileular line) and kidney 293T cells overexpressing ACE2 (293T-ACE2 cells).
Finally, the usage of a rank-primarily based totally pattern-matching method primarily based totally at the non-parametric and distribution-loose Kolmogorov-Smirnov statistic, the signatures had been queried in opposition to drug profiles from Connectivity Map (Cmap) – a aid that makes use of transcriptional expression records in probing relationships among diseases, mobileular physiology, and therapeutics.
Twenty-5 not unusualplace drug hits had been shared through at the least of the signatures (p = 0.0334), with 4 consensus drug hits (bacampicillin, clofazimine, haloperidol, valproic acid) throughout all 3 signatures (p = 0.0599) (A). Characterized not unusualplace hits through inspecting interactions with proteins in humans. Known drug objectives from DrugBank32 and expected extra objectives the usage of the similarity ensemble technique (SEA)33. Visualized the recognised interactions from DrugBank in a network
Overall, through utilising a various set of transcriptomic SARS-CoV-2 signatures throughout human mobileular line assays, the researchers diagnosed 25 capacity healing applicants from 102 specific drug hits. Further validation experiments found out SARS-CoV-2 antiviral interest for eleven of sixteen drug hits.
This take a look at confirms the strength of those predictive strategies and efficiently diagnosed exceptional clinically-authorised tablets with repurposing capacity for the remedy of COVID-19 – lots of which may be administered orally.
Hence, the variety of observed signatures and the overlap of highlighted tablets accentuates the software of the contemporary pipeline for unveiling tablets which have healing outcomes for a big range of SARS-CoV-2 contamination outcomes.
Still, numerous boundaries of this kind of technique have to be recognized. First and foremost, records generated from mobileular traces won’t efficiently constitute the organic modifications and manifold responses in human contamination. Moreover, the drug profiles from Cmap had been generated from mobileular line records.
Encouraged through those preliminary results, destiny studies endeavors on the subject have to acquire samples from a bigger pool of sufferers to achieve a far better gene expression signature and higher tell any remedy predictions.

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Also Read : CORONAVIRUS: RAPID REDUCTION IN NEW CASES, ONLY 36 THOUSAND PATIENTS ARRIVED IN 24 HOURS

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HT Rewind 2024: Teja Sajja says HanuMan kicking off the year in style is the moment he’d been ‘waiting for’ | Exclusive

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2 days ago

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December 21, 2024

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HT Rewind 2024: Teja Sajja says HanuMan kicking off the year in style is the moment he’d been ‘waiting for’ | Exclusive

In conversation with Hindustan Times, Teja Sajja decodes the success of HanuMan and other Telugu films, talks about his upcoming projects, and more.
When Prasanth Varma’s superhero film HanuMan, starring Teja Sajja, was announced to be released alongside big films like Mahesh Babu’s Guntur Kaaram, Venkatesh’s Saindhav and Nagarjuna’s Naa Saami Ranga in January this year, no one expected the underdog to emerge on top. And yet, the film, made on a budget of under ₹50 crore, managed to collect over ₹300 crore at the box office worldwide in 25 days, becoming one of the highest-grossing Indian films for the year. (Also Read: Ranveer Singh met HanuMan actor Teja Sajja, complimented him even after his Prasanth Varma film Rakshas got shelved)

Ask Teja about the moment he realised his film had not just fought against the tide but also risen to the top; he tells Hindustan Times in an exclusive conversation, “Since I returned to acting (as a lead actor after being a child artiste since 1998), this is the moment I’ve been waiting for. When everything from the HanuMan teaser to the songs was grabbing attention, we knew we had hit a gold mine. But I don’t think we imagined it would cross the ₹300 crore threshold. We were so satisfied with the opening numbers; everything else was a bonus.”

‘Success has given me fear of disappointing people’

Teja acted in Zombie Reddy, Ishq and Adbhutham before HanuMan, but they are what you would call ‘critical successes’, adding to his repertoire as an actor who can perform. But things have changed for him now, says Teja, who is being picky about the roles he says yes to. “Success either makes you overconfident or gives you the fear of disappointing people; I have the latter,” he explains.

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Teja admits he wants to chart out his career in Hrithik Roshan’s footsteps, but not in the way you think. “I have such a fondness for Hrithik due to Koi Mil Gaya and Krrish. No matter how well he performed after that, these left a lasting impression on me; I’m sure 90s kids will agree,” he says, adding, “Similarly, I’ve realised that I have an audience in children now. I want to be conscious of that when I pick roles. I want to make films families can enjoy together.”

But despite people in places like Mumbai or Delhi recognising him, Teja says he’s clear that he wants to cater to the Telugu audience first. “I am conscious that I am making films for my playground – the Telugu states. This is the sensibility I have grown up with, and I don’t know if I can cater to everyone else. Will I promote my films in other languages? Sure. But I also can’t be part of films that aren’t authentic to what I know or understand,” he explains.

‘Rootedness has put us on the world map’

And authenticity seems to be the need of the hour. Be it Baahubali and RRR or the recently released Pushpa 2: The Rule, Kalki 2898 AD and Devara: Part 1, certain kind of stories seem to be finding success. “Rootedness and going local is proving to be such a boon for us, be it in Devara or Pushpa or HanuMan. Kalki 2898 AD was our version of a Hollywood film (the sci-fi concept) with actors from across languages in predominant roles; it put us on the world map,” reflects Teja.

However, the actor admits Tollywood went through a phase of Bollywood-inspired rom-coms and family dramas that worked in their favour for a while. “That wasn’t easy to replicate either, but it’s just that these local stories are what the audience seems most interested in now. It can’t just be chalked up to religion, too. It’s about the morals these films are hinged on, the fighting for righteousness, and how an underdog can find their strength. Introducing Mahabharata or Ramayana to a new audience in a cool way is just a perk,” he says.

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And it’s this rootedness that Teja says his next films, Mirai and Jai Hanuman (the sequel to HanuMan), will also have ample of. “Mirai is also a superhero film that caters to kids, but it’s not an origin story like HanuMan. It has a pan-Asian and Buddhist touch because the story is based on King Ashoka’s ideologies. I hope that I will get to deliver something new to the audience again. I will only feel like I’ve arrived if Mirai is equally, if not more, successful,” says Teja.

Rishab Shetty will headline Jai Hanuman, but Teja also looks forward to shooting that. “I can’t wait to be on that set; it’ll be exciting. Now that we know India is ready to watch our films, I want to step it up. I want to shift gears and shoot for at least two films in 2025,” he says. As for what he will do next, Teja says he wants to up the ante. “When I got a SIIMA award for Zombie Reddy as a debutant, I remember telling Prasanth this would be the last award I get. But now that I won a Radio City Cine Award for Best Actor, I hope more awards will follow,” he signs off cheekily.

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