PMID- 32577638
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240329
DP  - 2020 Jul 28
TI  - Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives.
LID - 2020.06.08.140236 [pii]
LID - 10.1101/2020.06.08.140236 [doi]
AB  - Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused a 
      pandemic of historic proportions and continues to spread globally, with enormous 
      consequences to human health. Currently there is no vaccine, effective 
      therapeutic or prophylactic. Like other betacoronaviruses, attachment and entry 
      of SARS-CoV-2 is mediated by the spike glycoprotein (SGP). In addition to its 
      well-documented interaction with its receptor, human angiotensin converting 
      enzyme 2 (hACE2), SGP has been found to bind to glycosaminoglycans like heparan 
      sulfate, which is found on the surface of virtually all mammalian cells. Here, we 
      pseudotyped SARS-CoV-2 SGP on a third generation lentiviral (pLV) vector and 
      tested the impact of various sulfated polysaccharides on transduction efficiency 
      in mammalian cells. The pLV vector pseudotyped SGP efficiently and produced high 
      titers on HEK293T cells. Various sulfated polysaccharides potently neutralized 
      pLV-S pseudotyped virus with clear structure-based differences in anti-viral 
      activity and affinity to SGP. Concentration-response curves showed that pLV-S 
      particles were efficiently neutralized by a range of concentrations of 
      unfractionated heparin (UFH), enoxaparin, 6-O-desulfated UFH and 6-O-desulfated 
      enoxaparin with an IC(50) of 5.99 mug/L, 1.08 mg/L, 1.77 mug/L, and 5.86 mg/L 
      respectively. The low serum bioavailability of intranasally administered UFH, 
      along with data suggesting that the nasal epithelium is a portal for initial 
      infection and transmission, suggest that intranasal administration of UFH may be 
      an effective and safe prophylactic treatment.
FAU - Tandon, Ritesh
AU  - Tandon R
AD  - Department of Microbiology and Immunology, University of Mississippi Medical 
      Center, Jackson, MS 39216.
FAU - Sharp, Joshua S
AU  - Sharp JS
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
AD  - Department of Chemistry and Biochemistry, University of Mississippi, Oxford, MS 
      38677.
FAU - Zhang, Fuming
AU  - Zhang F
AD  - Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic 
      Institute, Troy, NY, 12180.
FAU - Pomin, Vitor H
AU  - Pomin VH
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
FAU - Ashpole, Nicole M
AU  - Ashpole NM
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
FAU - Mitra, Dipanwita
AU  - Mitra D
AD  - Department of Microbiology and Immunology, University of Mississippi Medical 
      Center, Jackson, MS 39216.
FAU - Jin, Weihua
AU  - Jin W
AD  - Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic 
      Institute, Troy, NY, 12180.
FAU - Liu, Hao
AU  - Liu H
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
FAU - Sharma, Poonam
AU  - Sharma P
AD  - Department of Microbiology and Immunology, University of Mississippi Medical 
      Center, Jackson, MS 39216.
FAU - Linhardt, Robert J
AU  - Linhardt RJ
AD  - Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic 
      Institute, Troy, NY, 12180.
LA  - eng
GR  - P30 GM122733/GM/NIGMS NIH HHS/United States
GR  - R01 GM127267/GM/NIGMS NIH HHS/United States
PT  - Preprint
DEP - 20200728
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
UIN - J Virol. 2021 Jan 13;95(3):. PMID: 33173010
PMC - PMC7302190
OTO - NOTNLM
OT  - COVID-19
OT  - Coronavirus
OT  - Glycosaminoglycans
OT  - Pseudotyping
OT  - Spike glycoprotein
EDAT- 2020/06/25 06:00
MHDA- 2020/06/25 06:01
PMCR- 2020/08/10
CRDT- 2020/06/25 06:00
PHST- 2020/06/25 06:00 [pubmed]
PHST- 2020/06/25 06:01 [medline]
PHST- 2020/06/25 06:00 [entrez]
PHST- 2020/08/10 00:00 [pmc-release]
AID - 2020.06.08.140236 [pii]
AID - 10.1101/2020.06.08.140236 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2020 Jul 28:2020.06.08.140236. doi: 
      10.1101/2020.06.08.140236.