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Heparin: A simplistic repurposing to prevent SARS-CoV-2 transmission in light of its in-vitro nanomolar efficacy.
Gupta, Yash; Maciorowski, Dawid; Zak, Samantha E; Kulkarni, Chandrashekhar V; Herbert, Andrew S; Durvasula, Ravi; Fareed, Jawed; Dye, John M; Kempaiah, Prakasha.
  • Gupta Y; Infectious Diseases, Mayo Clinic, Jacksonville, FL, USA.
  • Maciorowski D; Loyola University Chicago, Chicago, IL, USA.
  • Zak SE; United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA; The Geneva Foundation, 917 Pacific Avenue, Tacoma, WA, USA.
  • Kulkarni CV; School of Natural Sciences, University of Central Lancashire, Preston, UK.
  • Herbert AS; United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
  • Durvasula R; Infectious Diseases, Mayo Clinic, Jacksonville, FL, USA.
  • Fareed J; Department of Molecular Pharmacology & Neuroscience, Loyola University Chicago, Chicago, IL, USA.
  • Dye JM; United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA; The Geneva Foundation, 917 Pacific Avenue, Tacoma, WA, USA.
  • Kempaiah P; Infectious Diseases, Mayo Clinic, Jacksonville, FL, USA. Electronic address: Kempaiah.Prakasha@mayo.edu.
Int J Biol Macromol ; 183: 203-212, 2021 Jul 31.
Article in English | MEDLINE | ID: covidwho-1201630
ABSTRACT
The world is currently facing a novel coronavirus (SARS-CoV-2) pandemic. The greatest threat that is disrupting the normal functioning of society is the exceptionally high species independent transmission. Drug repurposing is understood to be the best strategy to immediately deploy well-characterized agents against new pathogens. Several repurposable drugs are already in evaluation for determining suitability to treat COVID-19. One such promising compound includes heparin, which is widely used in reducing thrombotic events associated with COVID-19 induced pathology. As part of identifying target-specific antiviral compounds among FDA and world-approved libraries using high-throughput virtual screening (HTVS), we previously evaluated top hits for anti-SARS-CoV-2 activity. Here, we report results of highly efficacious viral entry blocking properties of heparin (IC50 = 12.3 nM) in the complete virus assay, and further, propose ways to use it as a potential transmission blocker. Exploring further, our in-silico analysis indicated that the heparin interacts with post-translational glycoconjugates present on spike proteins. The patterns of accessible spike-glycoconjugates in open and closed states are completely contrasted by one another. Heparin-binding to the open conformation of spike structurally supports the state and may aid ACE2 binding as reported with cell surface-bound heparan sulfate. We also studied spike protein mutant variants' heparin interactions for possible resistance. Based on available data and optimal absorption properties by the skin, heparin could potentially be used to block SARS-CoV-2 transmission. Studies should be designed to exploit its nanomolar antiviral activity to formulate heparin as topical or inhalation-based formulations, particularly on exposed areas and sites of primary viremia e.g. ACE2 rich epithelia of the eye (conjunctiva/lids), nasal cavity, and mouth.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Heparin / Drug Repositioning / Spike Glycoprotein, Coronavirus / SARS-CoV-2 Type of study: Experimental Studies Topics: Variants Limits: Humans Language: English Journal: Int J Biol Macromol Year: 2021 Document Type: Article Affiliation country: J.ijbiomac.2021.04.148

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Heparin / Drug Repositioning / Spike Glycoprotein, Coronavirus / SARS-CoV-2 Type of study: Experimental Studies Topics: Variants Limits: Humans Language: English Journal: Int J Biol Macromol Year: 2021 Document Type: Article Affiliation country: J.ijbiomac.2021.04.148