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

Mittal, P.; Khandelwal, N.; Chander, Y.; Verma, A.; Kumar, R.; Putatunda, C.; Barua, S.; Gulati, B. R.; Kumar, N.

doi:10.1101/2023.09.27.559660

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bioRxiv · 10.1101/2023.09.27.559660

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

Mittal, P.·Khandelwal, N.·Chander, Y.·Verma, A.·Kumar, R.·Putatunda, C.·Barua, S.·Gulati, B. R.·Kumar, N.

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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- knockout Vero cells, together with enhanced viral yield in cells transfected with construct expressing p38, 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 addition, we demonstrated that long-term culture of SARS-CoV-2 in the presence of p38 inhibitor SB203580 does not easily select resistant viral mutants. In conclusion, we provide mechanistic insights on the regulation of SARS-CoV-2 replication by p38 MAPK.

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Mittal, P., Khandelwal, N., Chander, Y., Verma, A., Kumar, R., Putatunda, C., Barua, S., Gulati, B. R., Kumar, N.. 2023-09-27. p38-MAPK is prerequisite for the synthesis of SARS-CoV-2 protein. https://doi.org/10.1101/2023.09.27.559660

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