The carbohydrate-binding plant lectins and the non-peptidic antibiotic pradimicin A target the glycans of the coronavirus envelope glycoproteins.
OBJECTIVE
Many enveloped viruses carry carbohydrate-containing proteins on their surface. These glycoproteins are key to the infection process as they are mediators of the receptor binding and membrane fusion of the virion with the host cell. Therefore, they are attractive therapeutic targets for the development of novel antiviral therapies. Recently, carbohydrate-binding agents (CBA) were shown to possess antiviral activity towards coronaviruses. The current study further elucidates the inhibitory mode of action of CBA.


METHODS
Different strains of two coronaviruses, mouse hepatitis virus and feline infectious peritonitis virus, were exposed to CBA: the plant lectins Galanthus nivalis agglutinin, Hippeastrum hybrid agglutinin and Urtica dioica agglutinin (UDA) and the non-peptidic mannose-binding antibiotic pradimicin A.


CONCLUSIONS
Our results indicate that CBA target the two glycosylated envelope glycoproteins, the spike (S) and membrane (M) protein, of mouse hepatitis virus and feline infectious peritonitis virus. Furthermore, CBA did not inhibit virus-cell attachment, but rather affected virus entry at a post-binding stage. The sensitivity of coronaviruses towards CBA was shown to be dependent on the processing of the N-linked carbohydrates. Inhibition of mannosidases in host cells rendered the progeny viruses more sensitive to the mannose-binding agents and even to the N-acetylglucosamine-binding UDA. In addition, inhibition of coronaviruses was shown to be dependent on the cell-type used to grow the virus stocks. All together, these results show that CBA exhibit promising capabilities to inhibit coronavirus infections.
van der Meer
F J U M
FJ
Department of Infectious Diseases and Immunology, Division of Virology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
de Haan
C A M
CA
Schuurman
N M P
NM
Haijema
B J
BJ
Verheije
M H
MH
Bosch
B J
BJ
Balzarini
J
J
Egberink
H F
HF
D000818:Animals; D018943:Anthracyclines / Q000378:metabolism* / Q000494:pharmacology; D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology; D002415:Cats; D002460:Cell Line; D000086862:Coronavirus M Proteins; D016765:Coronavirus, Feline / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D006517:Murine hepatitis virus / Q000187:drug effects*; D037121:Plant Lectins / Q000378:metabolism* / Q000494:pharmacology; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000378:metabolism*; D053585:Virus Attachment / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects; D000095643:Pradimicins and Benanomicins
D018943:Anthracyclines; D000998:Antiviral Agents; D000086862:Coronavirus M Proteins; D008562:Membrane Glycoproteins; D037121:Plant Lectins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; C058036:pradimicin A; D000095643:Pradimicins and Benanomicins
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