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10.3390/ijms23126587

http://scihub22266oqcxt.onion/10.3390/ijms23126587
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35743031!9223907!35743031
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suck abstract from ncbi


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pmid35743031      Int+J+Mol+Sci 2022 ; 23 (12): ä
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  • Human Superantibodies to 3CL(pro) Inhibit Replication of SARS-CoV-2 across Variants #MMPMID35743031
  • Glab-Ampai K; Kaewchim K; Saenlom T; Thepsawat W; Mahasongkram K; Sookrung N; Chaicumpa W; Chulanetra M
  • Int J Mol Sci 2022[Jun]; 23 (12): ä PMID35743031show ga
  • Broadly effective and safe anti-coronavirus agent is existentially needed. Major protease (3CL(pro)) is a highly conserved enzyme of betacoronaviruses. The enzyme plays pivotal role in the virus replication cycle. Thus, it is a good target of a broadly effective anti-Betacoronavirus agent. In this study, human single-chain antibodies (HuscFvs) of the SARS-CoV-2 3CL(pro) were generated using phage display technology. The 3CL(pro)-bound phages were used to infect Escherichia coli host for the production the 3CL(pro)-bound HuscFvs. Computerized simulation was used to guide the selection of the phage infected-E. coli clones that produced HuscFvs with the 3CL(pro) inhibitory potential. HuscFvs of three phage infected-E. coli clones were predicted to form contact interface with residues for 3CL(pro) catalytic activity, substrate binding, and homodimerization. These HuscFvs were linked to a cell-penetrating peptide to make them cell-penetrable, i.e., became superantibodies. The superantibodies blocked the 3CL(pro) activity in vitro, were not toxic to human cells, traversed across membrane of 3CL(pro)-expressing cells to co-localize with the intracellular 3CL(pro) and most of all, they inhibited replication of authentic SARS-CoV-2 Wuhan wild type and alpha, beta, delta, and Omicron variants that were tested. The superantibodies should be investigated further towards clinical application as a safe and broadly effective anti-Betacoronavirus agent.
  • |*COVID-19 Drug Treatment[MESH]
  • |*SARS-CoV-2[MESH]
  • |Coronavirus 3C Proteases[MESH]
  • |Escherichia coli[MESH]
  • |Humans[MESH]


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