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dc.creatorMamidi, Prabhudutta
dc.creatorKumar Nayak, Tapas
dc.creatorKumar, Abhishek
dc.creatorKumar, Sameer
dc.creatorChatterjee, Sanchari
dc.creatorDe, Saikat
dc.creatorDatey, Ankita
dc.creatorLaha, Eshna
dc.creatorRay, Amrita
dc.creatorChattopadhyay, Subhasis
dc.creatorChattopadhyay, Soma
dc.date.accessioned2021-10-25T13:42:46Z
dc.date.available2021-10-25T13:42:46Z
dc.date.issued2021-05-26
dc.identifier.citationPrabhudutta Mamidi, Tapas Kumar Nayak, Abhishek Kumar, Sameer Kumar, Sanchari Chatterjee, Saikat De, Ankita Datey, Eshna Laha, Amrita Ray, Subhasis Chattopadhyay, Soma Chattopadhyay. MK2a inhibitor CMPD1 abrogates chikungunya virus infection by modulating actin remodeling pathway. bioRxiv 2021.05.26.445768; doi: https://doi.org/10.1101/2021.05.26.445768
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/6992
dc.identifier.urihttp://hdl.handle.net/20.500.12613/7011
dc.description.abstractChikungunya virus (CHIKV) epidemics around the world have created public health concern with the unavailability of effective drugs and vaccines. This emphasizes the need for molecular understanding of host-virus interactions for developing effective targeted antivirals. Microarray analysis was carried out using CHIKV strain (Prototype and Indian) infected Vero cells and two host isozymes, MK2 and MK3 were selected for further analysis. Gene silencing and drug treatment were performed in vitro and in vivo to unravel the role of MK2/MK3 in CHIKV infection. Gene silencing of MK2 and MK3 abrogated around 58% CHIKV progeny release from the host cell and a MK2 activation (a) inhibitor (CMPD1) treatment demonstrated 68% inhibition of viral infection suggesting a major role of MAPKAPKs during the late phase of CHIKV infection in vitro. Further, it was observed that the inhibition in viral infection is primarily due to the abrogation of lamellipodium formation through modulation of factors involved in the actin cytoskeleton remodeling pathway that is responsible for releasing the virus from the infected cells. Moreover, CHIKV-infected C57BL/6 mice demonstrated reduction in the viral copy number, lessened disease score and better survivability after CMPD1 treatment. In addition, reduction in expression of key pro-inflammatory mediators such as CXCL13, RAGE, FGF, MMP9 and increase in HGF (a CHIKV infection recovery marker) was observed indicating the effectiveness of this drug against CHIKV. Additionally, CMPD1 also inhibited HSV1 and SARS CoV2-19 infection in vitro. Taken together it can be proposed that MK2 and MK3 are crucial host factors for CHIKV infection and can be considered as key targets for developing effective anti-CHIKV strategies in future.
dc.format.extent36 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofCOVID-19 Research
dc.relation.isreferencedbybioRxiv
dc.rightsAttribution CC BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectChikungunya
dc.subjectAlphavirus
dc.subjectMK2
dc.subjectMK3
dc.subjectCMPD1
dc.titleMK2a inhibitor CMPD1 abrogates chikungunya virus infection by modulating actin remodeling pathway
dc.typeText
dc.type.genrePre-print
dc.contributor.groupCenter for Translational Medicine (Temple University)
dc.relation.doihttps://doi.org/10.1101/2021.05.26.445768
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeLewis Katz School of Medicine
dc.temple.creatorKumar Nayak, Tapas
refterms.dateFOA2021-10-25T13:42:46Z


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