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A Fungal Defensin Targets the SARS−CoV−2 Spike Receptor−Binding Domain
- Source :
- Journal of Fungi, Vol 7, Iss 553, p 553 (2021), Journal of Fungi, Volume 7, Issue 7
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Coronavirus Disease 2019 (COVID−19) elicited by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS−CoV−2) is calling for novel targeted drugs. Since the viral entry into host cells depends on specific interactions between the receptor−binding domain (RBD) of the viral Spike protein and the membrane−bound monocarboxypeptidase angiotensin converting enzyme 2 (ACE2), the development of high affinity RBD binders to compete with human ACE2 represents a promising strategy for the design of therapeutics to prevent viral entry. Here, we report the discovery of such a binder and its improvement via a combination of computational and experimental approaches. The binder micasin, a known fungal defensin from the dermatophytic fungus Microsporum canis with antibacterial activity, can dock to the crevice formed by the receptor−binding motif (RBM) of RBD via an extensive shape complementarity interface (855.9 Å2 in area) with numerous hydrophobic and hydrogen−bonding interactions. Using microscale thermophoresis (MST) technique, we confirmed that micasin and its C−terminal γ−core derivative with multiple predicted interacting residues exhibited a low micromolar affinity to RBD. Expanding the interface area of micasin through a single point mutation to 970.5 Å2 accompanying an enhanced hydrogen bond network significantly improved its binding affinity by six−fold. Our work highlights the naturally occurring fungal defensins as an emerging resource that may be suitable for the development into antiviral agents for COVID−19.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
antiviral drug
medicine.drug_class
QH301-705.5
coronavirus
Plant Science
010402 general chemistry
medicine.disease_cause
01 natural sciences
dermatophytic fungus
Article
03 medical and health sciences
micasin
Viral entry
medicine
Biology (General)
Defensin
Ecology, Evolution, Behavior and Systematics
Coronavirus
Microscale thermophoresis
Chemistry
Point mutation
SARS−CoV−2
0104 chemical sciences
Cell biology
030104 developmental biology
Angiotensin-converting enzyme 2
Antiviral drug
Antibacterial activity
Subjects
Details
- Language :
- English
- Volume :
- 7
- Issue :
- 553
- Database :
- OpenAIRE
- Journal :
- Journal of Fungi
- Accession number :
- edsair.doi.dedup.....9632c96e93e298f4ab12bb08b0ab90b5