Broad-spectrum in vitro activity and in vivo efficacy of the antiviral protein griffithsin against emerging viruses of the family Coronaviridae.
Viruses of the family Coronaviridae have recently emerged through zoonotic transmission to become serious human pathogens. The pathogenic agent responsible for severe acute respiratory syndrome (SARS), the SARS coronavirus (SARS-CoV), is a member of this large family of positive-strand RNA viruses that cause a spectrum of disease in humans, other mammals, and birds. Since the publicized outbreaks of SARS in China and Canada in 2002-2003, significant efforts successfully identified the causative agent, host cell receptor(s), and many of the pathogenic mechanisms underlying SARS. With this greater understanding of SARS-CoV biology, many researchers have sought to identify agents for the treatment of SARS. Here we report the utility of the potent antiviral protein griffithsin (GRFT) in the prevention of SARS-CoV infection both in vitro and in vivo. We also show that GRFT specifically binds to the SARS-CoV spike glycoprotein and inhibits viral entry. In addition, we report the activity of GRFT against a variety of additional coronaviruses that infect humans, other mammals, and birds. Finally, we show that GRFT treatment has a positive effect on morbidity and mortality in a lethal infection model using a mouse-adapted SARS-CoV and also specifically inhibits deleterious aspects of the host immunological response to SARS infection in mammals.
O'Keefe
Barry R
BR
Molecular Targets Development Program, Center for Cancer Research, NCI-Frederick, Frederick, Maryland 217021, USA. okeefeba@mail.nih.gov
Giomarelli
Barbara
B
Barnard
Dale L
DL
Shenoy
Shilpa R
SR
Chan
Paul K S
PK
McMahon
James B
JB
Palmer
Kenneth E
KE
Barnett
Brian W
BW
Meyerholz
David K
DK
Wohlford-Lenane
Christine L
CL
McCray
Paul B
PB
D020418:Algal Proteins / Q000494:pharmacology / Q000627:therapeutic use; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D002151:Calorimetry; D002460:Cell Line; D003332:Coronaviridae / Q000187:drug effects* / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D003333:Coronaviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D037102:Lectins / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000473:pathology / Q000821:virology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D037121:Plant Lectins; D011485:Protein Binding; D011487:Protein Conformation; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects / Q000378:metabolism; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000378:metabolism; D015047:Zoonoses
D020418:Algal Proteins; D000998:Antiviral Agents; D016207:Cytokines; D037102:Lectins; D008562:Membrane Glycoproteins; D037121:Plant Lectins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C499654:griffithsin protein, Griffithsia