Journal Article

PUBDB-2024-05777

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png SARS-CoV-2 Mpro oligomerization as a potential target for therapy

Lis, K. ; Plewka, J. ; Menezes, F. ; Bielecka, E. ; Chykunova, Y. ; Pustelny, K. ; Niebling, S.CFEL*CSSB*EMBL*Extern* ; Garcia, A. S. ; Garcia-Alai, M. ; Popowicz, G. M. ; Czarna, A. (Corresponding author)Extern* ; Kantyka, T. (Corresponding author) ; Pyrc, K. (Corresponding author)Extern*

2024
Elsevier New York, NY [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.ijbiomac.2024.131392  doi:10.3204/PUBDB-2024-05777

Abstract: The main protease (Mpro) of SARS-CoV-2 is critical in the virus's replication cycle, facilitating the maturation of polyproteins into functional units. Due to its conservation across taxa, Mpro is a promising target for broad-spectrum antiviral drugs. Targeting Mpro with small molecule inhibitors, such as nirmatrelvir combined with ritonavir (Paxlovid™), which the FDA has approved for post-exposure treatment and prophylaxis, can effectively interrupt the replication process of the virus. A key aspect of Mpro's function is its ability to form a functional dimer. However, the mechanics of dimerization and its influence on proteolytic activity remain less understood. In this study, we utilized biochemical, structural, and molecular modelling approaches to explore Mpro dimerization. We evaluated critical residues, specifically Arg4 and Arg298, that are essential for dimerization. Our results show that changes in the oligomerization state of Mpro directly affect its enzymatic activity and dimerization propensity. We discovered a synergistic relationship influencing dimer formation, involving both intra- and intermolecular interactions. These findings highlight the potential for developing allosteric inhibitors targeting Mpro, offering promising new directions for therapeutic strategies.

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Contributing Institute(s):

1. CSSB-CF-SPC (CSSB-CF-SPC)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)
2. CARE - Corona Accelerated R&D in Europe (101005077) (101005077)

Experiment(s):

1. No specific instrument

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article Lis, K. ; Plewka, J. ; Menezes, F. ; Bielecka, E. ; Chykunova, Y. ; Pustelny, K. ; Niebling, S. ; Garcia, A. S. ; Garcia-Alai, M. ; Popowicz, G. M. ; Nowak, J. S. ; Czarna, A. ; Kantyka, T. (Corresponding author) ; Pyrc, K. (Corresponding author)Extern*
Corrigendum to “SARS-CoV-2 Mpro oligomerization as a potential target for therapy” [Int. J. Biol. Macromol. 267 (Part 1) (May 2024) 131392]
International journal of biological macromolecules 276, 133473 (2024) [10.1016/j.ijbiomac.2024.133473]2024     Files BibTeX | EndNote: XML, Text | RIS

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