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p38-MAPK is prerequisite for the synthesis of SARS-CoV-2 protein

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Abstract

The inhibition of p38 mitogen-activated protein kinase (p38-MAPK) by small molecule chemical inhibitors was previously shown to impair severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, however, mechanisms underlying antiviral activity remains unexplored. In this study, reduced growth of SARS-CoV-2 in p38-α knockout Vero cells, together with enhanced viral yield in cells transfected with construct expressing p38α, suggested that p38-MAPK is essential for the propagation of SARS-CoV-2. The SARS-CoV-2 was also shown to induce phosphorylation (activation) of p38, at time when transcription/translational activities are considered to be at the peak levels. Further, we demonstrated that p38 supports viral RNA/protein synthesis without affecting viral attachment, entry, and budding in the target cells. In conclusion, we provide mechanistic insights on the regulation of SARS-CoV-2 replication by p38 MAPK.

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Acknowledgements

This work was supported by the Science and Engineering Research Board, Department of Science and Technology, Government of India (grant number CVD/2020/000103, CRG/2018/004747 and CRG/2019/000829 to N. Kumar and S. Barua). A part of this study belongs to the PhD thesis work of Priyasi Mittal.

Funding

This work was supported by Indian Council of Agricultural Research, New Delhi (grant number IXX14586 to N-Ku and NASF/ABA-8027/2020–21 to N-Ku and B.R.G.)

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Authors and Affiliations

  1. National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, Haryana, 125001, India

    Priyasi Mittal, Nitin Khandelwal, Yogesh Chander, Assim Verma, Ram Kumar, Sanjay Barua, Baldev Raj Gulati & Naveen Kumar

  2. Om Sterling Global University (OSGU), Hisar, Haryana, 125001, India

    Priyasi Mittal & Chayanika Putatunda

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  1. Priyasi Mittal
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Correspondence to Baldev Raj Gulati or Naveen Kumar.

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Mittal, P., Khandelwal, N., Chander, Y. et al. p38-MAPK is prerequisite for the synthesis of SARS-CoV-2 protein. VirusDis. (2024). https://doi.org/10.1007/s13337-024-00873-y

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