key: cord-0902658-lmfalzni authors: Sangith, Nikhil; Diagnotek, Xact title: Unique Fibrinogen-binding motifs in the Nucleocapsid Phosphoprotein of SARS CoV-2: Potential Implications in Host-Pathogen Interactions date: 2020-06-24 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110030 sha: c772a9ce8690719eeb56aae2ce9a74702b61532b doc_id: 902658 cord_uid: lmfalzni Novel Coronavirus (SARS CoV-2), the etiological agent for the highly contagious Corona virus disease-2019 (COVID-19) pandemic has threatened global health and economy infecting around 5.8 million people and causing over 359,200 deaths (as of 28(th) May, 2020, https://www.worldometers.info/coronavirus/). The clinical manifestations of infected patients generally range from asymptomatic or mild to severe illness, or even death. The ability of the virus to evade the host immune response have been major reasons for high morbidity and mortality. One of the important clinical observations under conditions of critical illness show increased risk of developing disseminated intravascular coagulation. Molecular mechanisms of how SARS CoV-2 induces such conditions still remain unclear. This report describes the presence of two unique motifs in the SARS CoV-2 nucleocapsid phosphoprotein (N-protein) that can potentially interact with fibrinogen and possibly prothrombin. This is based on an established function of secretory proteins in Staphylococcus aureus (S. aureus)- coagulase, Efb (Extracellular fibrinogen binding) and vWBP (von Willebrand factor Binding Protein), which are known to regulate the blood clotting cascade and the functions of host immune response. It is hypothesized that having protein interaction motifs that are homologous to these S. aureus proteins, the N-protein of this virus can mimic their functions, which may in turn play a crucial role in formation of blood clots in the host and help the virus evade host immune response. However, this hypothesis needs to be tested in vitro. Considering the overwhelming increase in the incidence of SARS CoV-2 infection globally, this information may be useful for further investigation and could help in deducing new therapeutic strategies to combat advanced stages of this disease. signalling pathways to escape from the host immune response. Fibrinogen interaction with coagulase and Efb of S. aureus is well established (5, 7) . The role of the fibrinogen-binding motif of N-protein in formation of blood clots and 142 mimicking functions of Efb for pathogen survival in host will be investigated. The 143 affinity of the motif towards fibrinogen will play a major role in regulating the functions 144 Coagulation disorders in coronavirus infected patients Journal of clinical virology : the 168 official publication of the Pan American Society for Abnormal coagulation parameters are associated with poor 170 prognosis in patients with novel coronavirus pneumonia Immune responses in COVID-19 and potential 173 vaccines: Lessons learned from SARS and MERS epidemic The SARS coronavirus 176 nucleocapsid protein--forms and functions Staphylococcus aureus Have a Common Fibrinogen Binding Motif Multiple ligands of von Willebrand factor-binding 181 protein (vWbp) promote Staphylococcus aureus clot formation in human plasma Binding of Efb from Staphylococcus 184 aureus to fibrinogen blocks neutrophil adherence Staphylococcus aureus secretes coagulase 187 and von Willebrand factor binding protein to modify the coagulation cascade and establish 188 host infections Fibrin(ogen)-alpha M beta 2 interactions regulate leukocyte 190 function and innate immunity in vivo Leukocyte engagement of fibrin(ogen) via the integrin 193 receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivo Phagocytosis escape by a Staphylococcus aureus 196 protein that connects complement and coagulation proteins at the bacterial surface Coronaviruses hijack the complement system of fibrinogen and in turn the host immune system. At this juncture, the knowledge of 145 existence of such a motif will help investigators to further probe and establish its role