Evidence map›Paper›PMID 39775571›Full record

ArticlePLoS pathogens2024

Withaferin A inhibits Chikungunya virus nsP2 protease and shows antiviral activity in the cell culture and mouse model of virus infection.

Kiran Bala Sharma, Chandru Subramani, Khashpatika Ganesh, Anshula Sharma, Brohmomoy Basu, Shivani Balyan, Ghanshyam Sharma, Shouri Ka, Arundhati Deb, Mitul Srivastava and 12 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Kiran Bala SharmaRegional Centre for Biotechnology, Faridabad, India.
Chandru SubramaniRegional Centre for Biotechnology, Faridabad, India.
Khashpatika GaneshRegional Centre for Biotechnology, Faridabad, India.
Anshula SharmaRegional Centre for Biotechnology, Faridabad, India.
Brohmomoy BasuRegional Centre for Biotechnology, Faridabad, India.
Shivani BalyanRegional Centre for Biotechnology, Faridabad, India.
Ghanshyam SharmaRegional Centre for Biotechnology, Faridabad, India.
Shouri KaRegional Centre for Biotechnology, Faridabad, India.
Arundhati DebRegional Centre for Biotechnology, Faridabad, India.
Mitul SrivastavaTranslational Health Science and Technology Institute, Faridabad, India.
Saurabh ChughTranslational Health Science and Technology Institute, Faridabad, India.
Sapna SehrawatRegional Centre for Biotechnology, Faridabad, India.
Kanchan BharadwajRegional Centre for Biotechnology, Faridabad, India.
Archana RoutRegional Centre for Biotechnology, Faridabad, India.
Pankaj Kumar SahooRegional Centre for Biotechnology, Faridabad, India.
Suman SauravRegional Centre for Biotechnology, Faridabad, India.
Rajender K MotianiRegional Centre for Biotechnology, Faridabad, India.
Ramandeep SinghTranslational Health Science and Technology Institute, Faridabad, India.
Deepti JainRegional Centre for Biotechnology, Faridabad, India.
Shailendra AsthanaTranslational Health Science and Technology Institute, Faridabad, India.
Renu WadhwaNational Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
Sudhanshu VratiRegional Centre for Biotechnology, Faridabad, India.ORCID 0000-0002-9984-3897

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus causing fever, myalgia, and debilitating joint swelling and pain, which in many patients becomes chronic. The frequent epidemics of CHIKV across the world pose a significant public health burden necessitating the development of effective antiviral therapeutics. A cellular imaging-based high-content screening of natural compounds identified withaferin A (WFA), a steroidal lactone isolated from the plant Withania somnifera, as a potent antiviral against CHIKV. In the ERMS cells, WFA inhibited CHIKV replication early during the life cycle by binding the CHIKV non-structural protein nsP2 and inhibiting its protease activity. This inhibited the viral polyprotein processing and the minus-sense viral RNA synthesis. WFA mounted the nsP2 protease inhibitory activity through its oxidising property as the reducing agents N-acetylcysteine and Glutathione-monoethyl ester effectively reversed the WFA-mediated protease inhibition in vitro and abolished the WFA-mediated antiviral activity in cultured cells. WFA inhibited CHIKV replication in the C57BL/6 mouse model of chikungunya disease, resulting in significantly lower viremia. Importantly, CHIKV-infected mice showed significant joint swelling which was not seen in WFA-treated mice. These data demonstrate the potential of WFA as a novel CHIKV antiviral.

Indexed as

Antiviral AgentsChikungunya FeverChikungunya virusVirus ReplicationWithanolidesAnimalsCysteine EndopeptidasesDisease Models, AnimalHumansMiceMice, Inbred C57BLViral Nonstructural ProteinsAntiviral AgentsCysteine EndopeptidasesnsP2 proteinaseViral Nonstructural Proteinswithaferin AWithanolides

Identifiers

PMID39775571
PMCPMC11723598

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.