He P et al. (2023), SPR Sensor-Based Analysis of the Inhibition of ...

ECB-ART-51404

Mar Drugs 2023 Apr 25;215:. doi: 10.3390/md21050264.

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SPR Sensor-Based Analysis of the Inhibition of Marine Sulfated Glycans on Interactions between Monkeypox Virus Proteins and Glycosaminoglycans.

He P , Shi D , Li Y , Xia K , Kim SB , Dwivedi R , Farrag M , Pomin VH , Linhardt RJ , Dordick JS , Zhang F .

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Sulfated glycans from marine organisms are excellent sources of naturally occurring glycosaminoglycan (GAG) mimetics that demonstrate therapeutic activities, such as antiviral/microbial infection, anticoagulant, anticancer, and anti-inflammation activities. Many viruses use the heparan sulfate (HS) GAG on the surface of host cells as co-receptors for attachment and initiating cell entry. Therefore, virion-HS interactions have been targeted to develop broad-spectrum antiviral therapeutics. Here we report the potential anti-monkeypox virus (MPXV) activities of eight defined marine sulfated glycans, three fucosylated chondroitin sulfates, and three sulfated fucans extracted from the sea cucumber species Isostichopus badionotus, Holothuria floridana, and Pentacta pygmaea, and the sea urchin Lytechinus variegatus, as well as two chemically desulfated derivatives. The inhibitions of these marine sulfated glycans on MPXV A29 and A35 protein-heparin interactions were evaluated using surface plasmon resonance (SPR). These results demonstrated that the viral surface proteins of MPXV A29 and A35 bound to heparin, which is a highly sulfated HS, and sulfated glycans from sea cucumbers showed strong inhibition of MPXV A29 and A35 interactions. The study of molecular interactions between viral proteins and host cell GAGs is important in developing therapeutics for the prevention and treatment of MPXV.

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	Figure 1. Chemical structures of heparin and marine sulfated glycans.
	Figure 2. Amino acid sequence of MPXV A29 and A35 proteins (positively charged amino acids histidine (H), lysine (K), and arginine (R) are in red) and SPR sensorgrams of MPXV A29 and A35 protein binding with heparin. Concentrations of A35 protein were 1000, 500, 250, 125, 62.5 and 31.3 nM (from top to bottom, respectively).
	Figure 3. Solution competition between heparin and heparin Ib glycans. (A) SPR sensorgrams of the MPXV A35 protein–heparin interaction competing with different Ib glycans. The concentration of the MPXV A35 protein was 250 nM mixed with 100 µg/mL of different Ib glycans. (B) Bar graphs (based on triplicate experiments with standard deviation) of normalized MPXV A35 protein binding preference to surface heparin by competing with different Ib glycans. (C) SPR sensorgrams of the MPXV A29 protein–heparin interaction competing with different Ib glycans. The concentration of the MPXV A29 protein was 250 nM mixed with 100 µg/mL of different Ib glycans. (D) Bar graphs (based on triplicate experiments with standard deviations) of the normalized MPXV A29 protein binding preference to surface heparin by competing with different Ib glycans. Statistical analysis was performed using an unpaired two-tailed t-test (: p ≤ 0.05 compared with the control, *: p ≤ 0.01 compared with the control).
	Figure 4. Solution competition between heparin and Hf glycans. (A) SPR sensorgrams of the MPXV A35 protein–heparin interaction competing with different Hf glycans. The concentration of the MPXV A35 protein was 250 nM mixed with 100 µg/mL of different Hf glycans. (B) Bar graphs (based on triplicate experiments with standard deviations) of the normalized MPXV A35 protein binding preference to surface heparin by competing with different Hf glycans. (C) SPR sensorgrams of the MPXV A29 protein–heparin interaction competing with different Hf glycans. The concentration of the MPXV A29 protein was 250 nM mixed with 100 µg/mL of different Hf glycans. (D) Bar graphs (based on triplicate experiments with standard deviations) of the normalized MPXV A29 protein binding preference to surface heparin by competing with different Hf glycans. Statistical analysis was performed using an unpaired two-tailed t-test (: p ≤ 0.05 compared with the control, *: p ≤ 0.01 compared with the control).
	Figure 5. Solution competition between heparin and LvSF and PpFucCS glycans. (A) SPR sensorgrams of the MPXV A35 protein–heparin interaction competition with different LvSF and PpFucCS glycans. The concentration of the MPXV A35 protein was 250 nM mixed with 100 µg/mL of different LvSF and PpFucCS glycans. (B) Bar graphs (based on triplicate experiments with standard deviations) of the normalized MPXV A35 protein binding preference to surface heparin by competing with different LvSF and PpFucCS glycans. (C) SPR sensorgrams of the MPXV A29 protein–heparin interaction competing with different LvSF and PpFucCS glycans. The concentration of the MPXV A29 protein was 250 nM mixed with 100 µg/mL of different LvSF and PpFucCS glycans. (D) Bar graphs (based on triplicate experiments with standard deviations) of the normalized MPXV A29 protein binding preference to surface heparin by competing with different LvSF and PpFucCS glycans. Statistical analysis was performed using an unpaired two-tailed t-test (*: p ≤ 0.05 compared with the control).

References [+] :

Ahmed, Vaccinia-Virus-Based Vaccines Are Expected to Elicit Highly Cross-Reactive Immunity to the 2022 Monkeypox Virus. 2022, Pubmed