Sars-cov-2 inhibition by sulfonated compounds

Article

Reference

Sars-cov-2 inhibition by sulfonated compounds

GASBARRI, Matteo, et al.

Abstract

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) depends on angiotensin converting enzyme 2 (ACE2) for cellular entry, but it might also rely on attachment receptors such as heparan sulfates. Several groups have recently demonstrated an affinity of the SARS-CoV2 spike protein for heparan sulfates and a reduced binding to cells in the presence of heparin or heparinase treatment. Here, we investigated the inhibitory activity of several sulfated and sulfonated molecules, which prevent interaction with heparan sulfates, against vesicular stomatitis virus (VSV)-pseudotyped-SARS-CoV-2 and the authentic SARS-CoV-2. Sulfonated cyclodextrins and nanoparticles that have recently shown broad-spectrum non-toxic virucidal activity against many heparan sulfates binding viruses showed inhibitory activity in the micromolar and nanomolar ranges, respectively. In stark contrast with the mechanisms that these compounds present for these other viruses, the inhibition against SARS-CoV-2 was found to be simply reversible.

GASBARRI, Matteo, et al . Sars-cov-2 inhibition by sulfonated compounds. Microorganisms , 2020

DOI : 10.3390/microorganisms8121894

Available at:

http://archive-ouverte.unige.ch/unige:145476

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a) 1H-NMR b) TEM image c) Size distribution

Figure S1. Characterization of MUS:OT NPs. (a) Ratio between MUS:OT was calculated by 1H-NMR (400 MHz, Bruker AVANCE 400). The ratio between MUS:OT was determined to be 24% OT and 76%

MUS. (b) TEM image of AuNPs taken by Tecnai Osiris Size of the core was evaluated using a ImageJ plug-in analyzing more than 10000 particles. (c) The diameter of the core is 3.5  1 nm. MW can be estimated to be around 320kDa.

a)

b)

Molecular Formula Theoretical (Da) Experimental (Da) Error (ppm)

(C119H217O49S17)7- 411.1518 411.1523 1.6

(C119H218O49S17)6- 479.8448 479.8440 1.7

(C119H219O49S17)5- 576.0152 576.0142 1.9

(C119H220O49S17)4- 720.2709 720.2697 1.6

(C119H221O49S17)3- 960.6969 960.6948 2.2

c)

200 300 400 500 600 700 800 900 1000

0,0 5,0x10³ 1,0x10⁴ 1,5x10⁴ 2,0x10⁴ 2,5x10⁴ 3,0x10⁴ 3,5x10⁴ 4,0x10⁴ 4,5x10⁴

Intensity

m/z 411.1518

479.8440

576.0142 720.2697 (C₁₁₉H₂₁₇O₄₉S₁₇)^7-

(C₁₁₉H₂₁₈O₄₉S₁₇)^6-

(C₁₁₉H₂₁₉O₄₉S₁₇)^5- (C₁₁₉H₂₂₀O₄₉S₁₇)^4-

Figure S2. Characterization of MUS CD. (a) HRMS Cold-Spray Ionisation spectrum of MUS-CD in EtOH/H2O (50:50), (b) HRMS Summary of MUS-CD in EtOH/H2O (50:50). Values correspond to the monoisotopic mass, (c) CE-UV electropherogram of MUS-CD at 230 nm with assigned CD species showing 100% of 7 sulfonates per CD.

Figure S3. Inhibitory activity of sulfonated nanomaterial against SARS-CoV2. SARS-CoV-2 was incubated for 1h at 37°C with different doses of MUS:OT and MUS CD and subsequently serially added on cells. Number of plaques was determined 48hpi. Results are expressed as mean and SEM of two independent experiments.

3 4 5 6 7 8 9 10

75 80 85 90 95 100 105 110 115 120 125

UV / mAU

7

Time / min

-1 0 1 2 3

0 50 100

Log mg/mL

% o f in fe c ti o n