A Procoagulant Peptide Analog of the SARS-CoV-2 Nucleocapsid C-terminal Domain

Abstract

BackgroundUncontrolled bleeding complicates trauma, surgery and many medical conditions. While currently available procoagulant therapies (e.g., plasma-derived factors, recombinant proteins, antifibrinolytics) have crucial limitations. MethodsN389 (CQQTVTLLPAADLDDFSC) was synthesized by Fmoc solid-phase chemistry, characterized by HPLC and LC-MS, then tested in normal human pooled plasma in microplate mechanical clot-formation assays using incubated and immediate addition formats. Kinetic parameters (plasma recalcification, PRT; maximum absorbance, Amax) were obtained from absorbance curves fit to four-parameter logistic models. Mixing studies with modified (i.e., aged, adsorbed) plasma probed factor dependence. ResultsIn plasma coagulation assays activated with 25 mM CaCl{square}, baseline clotting showed a PRT of 23.74 {+/-} 0.27 min and Amax of 0.1813 {+/-} 0.0043 (n = 3), whereas N389 significantly reduced PRT to 8.442 {+/-} 6.0395 min without incubation (p = 0.0012), further decreased PRT after incubation (p View larger version (29K): org.highwire.dtl.DTLVardef@1f8e8beorg.highwire.dtl.DTLVardef@78170forg.highwire.dtl.DTLVardef@31f4b2org.highwire.dtl.DTLVardef@1b7eef0_HPS_FORMAT_FIGEXP M_FIG C_FIG