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The SARS-CoV-2 SSHHPS Recognized by the Papain-like Protease.
Reynolds, Nathanael D; Aceves, Nathalie M; Liu, Jinny L; Compton, Jaimee R; Leary, Dagmar H; Freitas, Brendan T; Pegan, Scott D; Doctor, Katarina Z; Wu, Fred Y; Hu, Xin; Legler, Patricia M.
  • Reynolds ND; Center for Bio/molecular Science and Engineering (CBMSE), U.S. Naval Research Laboratory, 4555 Overlook Avenue, Washington, DC 20375, United States.
  • Aceves NM; California State University, Fresno, California 93740, United States.
  • Liu JL; Center for Bio/molecular Science and Engineering (CBMSE), U.S. Naval Research Laboratory, 4555 Overlook Avenue, Washington, DC 20375, United States.
  • Compton JR; Center for Bio/molecular Science and Engineering (CBMSE), U.S. Naval Research Laboratory, 4555 Overlook Avenue, Washington, DC 20375, United States.
  • Leary DH; Center for Bio/molecular Science and Engineering (CBMSE), U.S. Naval Research Laboratory, 4555 Overlook Avenue, Washington, DC 20375, United States.
  • Freitas BT; Center for Drug Discovery, College of Pharmacy, University of Georgia, Athens, Georgia 30602, United States.
  • Pegan SD; Center for Drug Discovery, College of Pharmacy, University of Georgia, Athens, Georgia 30602, United States.
  • Doctor KZ; Navy Center for Applied Research in AI (NCARAI) Information Technology Division, U.S. Naval Research Laboratory, 4555 Overlook Ave., Washington, DC 20375, United States.
  • Wu FY; Indiana University Health Systems, Indiana University School of Medicine, Bloomington, Indiana 47401, United States.
  • Hu X; National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland 20850, United States.
  • Legler PM; Center for Bio/molecular Science and Engineering (CBMSE), U.S. Naval Research Laboratory, 4555 Overlook Avenue, Washington, DC 20375, United States.
ACS Infect Dis ; 7(6): 1483-1502, 2021 06 11.
Article in English | MEDLINE | ID: covidwho-1387146
ABSTRACT
Viral proteases are highly specific and recognize conserved cleavage site sequences of ∼6-8 amino acids. Short stretches of homologous host-pathogen sequences (SSHHPS) can be found spanning the viral protease cleavage sites. We hypothesized that these sequences corresponded to specific host protein targets since >40 host proteins have been shown to be cleaved by Group IV viral proteases and one Group VI viral protease. Using PHI-BLAST and the viral protease cleavage site sequences, we searched the human proteome for host targets and analyzed the hit results. Although the polyprotein and host proteins related to the suppression of the innate immune responses may be the primary targets of these viral proteases, we identified other cleavable host proteins. These proteins appear to be related to the virus-induced phenotype associated with Group IV viruses, suggesting that information about viral pathogenesis may be extractable directly from the viral genome sequence. Here we identify sequences cleaved by the SARS-CoV-2 papain-like protease (PLpro) in vitro within human MYH7 and MYH6 (two cardiac myosins linked to several cardiomyopathies), FOXP3 (an X-linked Treg cell transcription factor), ErbB4 (HER4), and vitamin-K-dependent plasma protein S (PROS1), an anticoagulation protein that prevents blood clots. Zinc inhibited the cleavage of these host sequences in vitro. Other patterns emerged from multispecies sequence alignments of the cleavage sites, which may have implications for the selection of animal models and zoonosis. SSHHPS/nsP is an example of a sequence-specific post-translational silencing mechanism.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptide Hydrolases / Papain / Viral Proteases / SARS-CoV-2 Limits: Humans Language: English Journal: ACS Infect Dis Year: 2021 Document Type: Article Affiliation country: ACSINFECDIS.0C00866

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Peptide Hydrolases / Papain / Viral Proteases / SARS-CoV-2 Limits: Humans Language: English Journal: ACS Infect Dis Year: 2021 Document Type: Article Affiliation country: ACSINFECDIS.0C00866